1st Semester 74 - BIOLOGY JUNCTION

Chapter 1 – Exploring Life – Lecture Outline

Chapter 1 Exploring Life Lecture Outline

Overview: Biology’s Most Exciting Era

Biology is the scientific study of life.
You are starting your study of biology during its most exciting era.
The largest and best-equipped community of scientists in history is beginning to solve problems that once seemed unsolvable.
Biology is an ongoing inquiry about the nature of life.
Biologists are moving closer to understanding:
How a single cell develops into an adult animal or plant.
How plants convert solar energy into the chemical energy of food.
How the human mind works.
How living things interact in biological communities.
How the diversity of life evolved from the first microbes.
Research breakthroughs in genetics and cell biology are transforming medicine and agriculture.
Neuroscience and evolutionary biology are reshaping psychology and sociology.
Molecular biology is providing new tools for anthropology and criminology.
New models in ecology are helping society to evaluate environmental issues, such as the causes and biological consequences of global warming.
Unifying themes pervade all of biology.

Concept 1.1 Biologists explore life from the microscopic to the global scale

Life’s basic characteristic is a high degree of order.
Each level of biological organization has emergent properties.
Biological organization is based on a hierarchy of structural levels, each building on the levels below.
At the lowest level are atoms that are ordered into complex biological molecules.
Biological molecules are organized into structures called organelles, the components of cells.
Cells are the fundamental unit of structure and function of living things.
Some organisms consist of a single cell; others are multicellular aggregates of specialized cells.
Whether multicellular or unicellular, all organisms must accomplish the same functions: uptake and processing of nutrients, excretion of wastes, response to environmental stimuli, and reproduction.
Multicellular organisms exhibit three major structural levels above the cell: similar cells are grouped into tissues, several tissues coordinate to form organs, and several organs form an organ system.
For example, to coordinate locomotory movements, sensory information travels from sense organs to the brain, where nervous tissues composed of billions of interconnected neurons—supported by connective tissue—coordinate signals that travel via other neurons to the individual muscle cells.
Organisms belong to populations, localized groups of organisms belonging to the same species.
Populations of several species in the same area comprise a biological community.
Populations interact with their physical environment to form an ecosystem.
The biosphere consists of all the environments on Earth that are inhabited by life.
Organisms interact continuously with their environment.
Each organism interacts with its environment, which includes other organisms as well as nonliving factors.
Both organism and environment are affected by the interactions between them.
The dynamics of any ecosystem include two major processes: the cycling of nutrients and the flow of energy from sunlight to producers to consumers.
In most ecosystems, producers are plants and other photosynthetic organisms that convert light energy to chemical energy.
Consumers are organisms that feed on producers and other consumers.
All the activities of life require organisms to perform work, and work requires a source of energy.
The exchange of energy between an organism and its environment often involves the transformation of energy from one form to another.
In all energy transformations, some energy is lost to the surroundings as heat.
In contrast to chemical nutrients, which recycle within an ecosystem, energy flows through an ecosystem, usually entering as light and exiting as heat.
Cells are an organism’s basic unit of structure and function.
The cell is the lowest level of structure that is capable of performing all the activities of life.
For example, the ability of cells to divide is the basis of all reproduction and the basis of growth and repair of multicellular organisms.
Understanding how cells work is a major research focus of modern biology.
At some point, all cells contain deoxyribonucleic acid, or DNA, the heritable material that directs the cell’s activities.
DNA is the substance of genes, the units of inheritance that transmit information from parents to offspring.
Each of us began life as a single cell stocked with DNA inherited from our parents.
DNA in human cells is organized into chromosomes.
Each chromosome has one very long DNA molecule, with hundreds or thousands of genes arranged along its length.
The DNA of chromosomes replicates as a cell prepares to divide.
Each of the two cellular offspring inherits a complete set of genes.
In each cell, the genes along the length of DNA molecules encode the information for building the cell’s other molecules.
DNA thus directs the development and maintenance of the entire organism.
Most genes program the cell’s production of proteins.
Each DNA molecule is made up of two long chains arranged in a double helix.
Each link of a chain is one of four nucleotides, encoding the cell’s information in chemical letters.
The sequence of nucleotides along each gene codes for a specific protein with a unique shape and function.
Almost all cellular activities involve the action of one or more proteins.
DNA provides the heritable blueprints, but proteins are the tools that actually build and maintain the cell.
All forms of life employ essentially the same genetic code.
Because the genetic code is universal, it is possible to engineer cells to produce proteins normally found only in some other organism.
The library of genetic instructions that an organism inherits is called its genome.
The chromosomes of each human cell contain about 3 billion nucleotides, including genes coding for more than 70,000 kinds of proteins, each with a specific function.
Every cell is enclosed by a membrane that regulates the passage of material between a cell and its surroundings.
Every cell uses DNA as its genetic material.
There are two basic types of cells: prokaryotic cells and eukaryotic cells.
The cells of the microorganisms called bacteria and archaea are prokaryotic.
All other forms of life have more complex eukaryotic cells.
Eukaryotic cells are subdivided by internal membranes into various organelles.
In most eukaryotic cells, the largest organelle is the nucleus, which contains the cell’s DNA as chromosomes.
The other organelles are located in the cytoplasm, the entire region between the nucleus and outer membrane of the cell.
Prokaryotic cells are much simpler and smaller than eukaryotic cells.
In a prokaryotic cell, DNA is not separated from the cytoplasm in a nucleus.
There are no membrane-enclosed organelles in the cytoplasm.
All cells, regardless of size, shape, or structural complexity, are highly ordered structures that carry out complicated processes necessary for life.

Concept 1.2 Biological systems are much more than the sum of their parts

“The whole is greater than the sum of its parts.”
The combination of components can form a more complex organization called a system.
Examples of biological systems are cells, organisms, and ecosystems.
Consider the levels of life.
With each step upward in the hierarchy of biological order, novel properties emerge that are not present at lower levels.
These emergent properties result from the arrangements and interactions between components as complexity increases.
A cell is much more than a bag of molecules.
Our thoughts and memories are emergent properties of a complex network of neurons.
This theme of emergent properties accents the importance of structural arrangement.
The emergent properties of life are not supernatural or unique to life but simply reflect a hierarchy of structural organization.
The emergent properties of life are particularly challenging because of the unparalleled complexity of living systems.
The complex organization of life presents a dilemma to scientists seeking to understand biological processes.
We cannot fully explain a higher level of organization by breaking it down into its component parts.
At the same time, it is futile to try to analyze something as complex as an organism or cell without taking it apart.
Reductionism, reducing complex systems to simpler components, is a powerful strategy in biology.
The Human Genome Project—the sequencing of the genome of humans and many other species—is heralded as one of the greatest scientific achievements ever.
Research is now moving on to investigate the function of genes and the coordination of the activity of gene products.
Biologists are beginning to complement reductionism with new strategies for understanding the emergent properties of life—how all of the parts of biological systems are functionally integrated.
The ultimate goal of systems biology is to model the dynamic behavior of whole biological systems.
Accurate models allow biologists to predict how a change in one or more variables will impact other components and the whole system.
Scientists investigating ecosystems pioneered this approach in the 1960s with elaborate models diagramming the interactions of species and nonliving components in ecosystems.
Systems biology is now becoming increasingly important in cellular and molecular biology, driven in part by the deluge of data from the sequencing of genomes and our increased understanding of protein functions.
In 2003, a large research team published a network of protein interactions within a cell of a fruit fly.
Three key research developments have led to the increased importance of systems biology.

1.           High-throughput technology. Systems biology depends on methods that can analyze biological materials very quickly and produce enormous amounts of data. An example is the automatic DNA-sequencing machines used by the Human Genome Project.
2.           Bioinformatics. The huge databases from high-throughput methods require computing power, software, and mathematical models to process and integrate information.
3.           Interdisciplinary research teams. Systems biology teams may include engineers, medical scientists, physicists, chemists, mathematicians, and computer scientists as well as biologists.

Regulatory mechanisms ensure a dynamic balance in living systems.
Chemical processes within cells are accelerated, or catalyzed, by specialized protein molecules, called enzymes.
Each type of enzyme catalyzes a specific chemical reaction.
In many cases, reactions are linked into chemical pathways, each step with its own enzyme.
How does a cell coordinate its various chemical pathways?
Many biological processes are self-regulating: the output or product of a process regulates that very process.
In negative feedback, or feedback inhibition, accumulation of an end product of a process slows or stops that process.
Though less common, some biological processes are regulated by positive feedback, in which an end product speeds up its own production.
Feedback is common to life at all levels, from the molecular level to the biosphere.
Such regulation is an example of the integration that makes living systems much greater than the sum of their parts.

Concept 1.3 Biologists explore life across its great diversity of species

Biology can be viewed as having two dimensions: a “vertical” dimension covering the size scale from atoms to the biosphere and a “horizontal” dimension that stretches across the diversity of life.
The latter includes not only present-day organisms, but also those that have existed throughout life’s history.
Living things show diversity and unity.
Life is enormously diverse.
Biologists have identified and named about 1.8 million species.
This diversity includes 5,200 known species of prokaryotes, 100,000 fungi, 290,000 plants, 50,000 vertebrates, and 1,000,000 insects.
Thousands of newly identified species are added each year.
Estimates of the total species count range from 10 million to more than 200 million.
In the face of this complexity, humans are inclined to categorize diverse items into a smaller number of groups.
Taxonomy is the branch of biology that names and classifies species into a hierarchical order.
Until the past decade, biologists divided the diversity of life into five kingdoms.
New methods, including comparisons of DNA among organisms, have led to a reassessment of the number and boundaries of the kingdoms.
Various classification schemes now include six, eight, or even dozens of kingdoms.
Coming from this debate has been the recognition that there are three even higher levels of classifications, the domains.
the three domains are Bacteria, Archaea, and Eukarya.
The first two domains, domain Bacteria and domain Archaea, consist of prokaryotes.
All the eukaryotes are now grouped into various kingdoms of the domain Eukarya.
The recent taxonomic trend has been to split the single-celled eukaryotes and their close relatives into several kingdoms.
Domain Eukarya also includes the three kingdoms of multicellular eukaryotes: the kingdoms Plantae, Fungi, and Animalia.
These kingdoms are distinguished partly by their modes of nutrition.
Most plants produce their own sugars and food by photosynthesis.
Most fungi are decomposers that absorb nutrients by breaking down dead organisms and organic wastes.
Animals obtain food by ingesting other organisms.
Underlying the diversity of life is a striking unity, especially at the lower levels of organization.
The universal genetic language of DNA unites prokaryotes and eukaryotes.
Among eukaryotes, unity is evident in many details of cell structure.
Above the cellular level, organisms are variously adapted to their ways of life.
How do we account for life’s dual nature of unity and diversity?
The process of evolution explains both the similarities and differences among living things.

Concept 1.4 Evolution accounts for life’s unity and diversity

The history of life is a saga of a changing Earth billions of years old, inhabited by a changing cast of living forms.
Charles Darwin brought evolution into focus in 1859 when he presented two main concepts in one of the most important and controversial books ever written, On the Origin of Species by Natural Selection.
Darwin ’s first point was that contemporary species arose from a succession of ancestors through “descent with modification.”
This term captured the duality of life’s unity and diversity: unity in the kinship among species that descended from common ancestors and diversity in the modifications that evolved as species branched from their common ancestors.
Darwin ’s second point was his mechanism for descent with modification: natural selection.
Darwin inferred natural selection by connecting two observations:
Observation 1: Individual variation. Individuals in a population of any species vary in many heritable traits.
Observation 2: Overpopulation and competition. Any population can potentially produce far more offspring than the environment can support. This creates a struggle for existence among variant members of a population.
Inference: Unequal reproductive success. Darwin inferred that those individuals with traits best suited to the local environment would leave more healthy, fertile offspring.
Inference: Evolutionary adaptation. Unequal reproductive success can lead to adaptation of a population to its environment. Over generations, heritable traits that enhance survival and reproductive success will tend to increase in frequency among a population’s individuals. The population evolves.
Natural selection, by its cumulative effects over vast spans of time, can produce new species from ancestral species.
For example, a population fragmented into several isolated populations in different environments may gradually diversify into many species as each population adapts over many generations to different environmental problems.
Fourteen species of finches found on the Galápagos Islands diversified after an ancestral finch species reached the archipelago from the South American mainland.
Each species is adapted to exploit different food sources on different islands.
Biologists’ diagrams of evolutionary relationships generally take a treelike form.
Just as individuals have a family tree, each species is one twig of a branching tree of life.
Similar species like the Galápagos finches share a recent common ancestor.
Finches share a more distant ancestor with all other birds.
The common ancestor of all vertebrates is even more ancient.
Trace life back far enough, and there is a shared ancestor of all living things.
All of life is connected through its long evolutionary history.

Concept 1.5 Biologists use various forms of inquiry to explore life

The word science is derived from a Latin verb meaning “to know.”
At the heart of science is inquiry, people asking questions about nature and focusing on specific questions that can be answered.
The process of science blends two types of exploration: discovery science and hypothesis-based science.
Discovery science is mostly about discovering nature.
Hypothesis-based science is mostly about explaining nature.
Most scientific inquiry combines the two approaches.
Discovery science describes natural structures and processes as accurately as possible through careful observation and analysis of data.
Discovery science built our understanding of cell structure and is expanding our databases of genomes of diverse species.
Observation is the use of the senses to gather information, which is recorded as data.
Data can be qualitative or quantitative.
Quantitative data are numerical measurements.
Qualitative data may be in the form of recorded descriptions.
Jane Goodall has spent decades recording her observations of chimpanzee behavior during field research in Gambia .
She has also collected volumes of quantitative data over that time.
Discovery science can lead to important conclusions based on inductive reasoning.
Through induction, we derive generalizations based on a large number of specific observations.
In science, inquiry frequently involves the proposing and testing of hypotheses.
A hypothesis is a tentative answer to a well-framed question.
It is usually an educated postulate, based on past experience and the available data of discovery science.
A scientific hypothesis makes predictions that can be tested by recording additional observations or by designing experiments.
A type of logic called deduction is built into hypothesis-based science.
In deductive reasoning, reasoning flows from the general to the specific.
From general premises, we extrapolate to a specific result that we should expect if the premises are true.
In hypothesis-based science, deduction usually takes the form of predictions about what we should expect if a particular hypothesis is correct.
We test the hypothesis by performing the experiment to see whether or not the results are as predicted.
Deductive logic takes the form of “If . . . then” logic.
Scientific hypotheses must be testable.
There must be some way to check the validity of the idea.
Scientific hypotheses must be falsifiable.
There must be some observation or experiment that could reveal if a hypothesis is actually not true.
The ideal in hypothesis-based science is to frame two or more alternative hypotheses and design experiments to falsify them.
No amount of experimental testing can prove a hypothesis.
A hypothesis gains support by surviving various tests that could falsify it, while testing falsifies alternative hypotheses.
Facts, in the form of verifiable observations and repeatable experimental results, are the prerequisites of science.
We can explore the scientific method.
There is an idealized process of inquiry called the scientific method.
Very few scientific inquiries adhere rigidly to the sequence of steps prescribed by the textbook scientific method.
Discovery science has contributed a great deal to our understanding of nature without most of the steps of the so-called scientific method.
We will consider a case study of scientific research.
This case begins with a set of observations and generalizations from discovery science.
Many poisonous animals have warning coloration that signals danger to potential predators.
Imposter species mimic poisonous species, although they are harmless.
An example is the bee fly, a nonstinging insect that mimics a honeybee.
What is the function of such mimicry? What advantage does it give the mimic?
In 1862, Henry Bates proposed that mimics benefit when predators mistake them for harmful species.
This deception may lower the mimic’s risk of predation.
In 2001, David and Karin Pfennig and William Harcombe of the University of North Carolina designed a set of field experiments to test Bates’s mimicry hypothesis.
In North and South Carolina , a poisonous snake called the eastern coral snake has warning red, yellow, and black coloration.
Predators avoid these snakes. It is unlikely that predators learn to avoid coral snakes, as a strike is usually lethal.
Natural selection may have favored an instinctive recognition and avoidance of the warning coloration of the coral snake.
The nonpoisonous scarlet king snake mimics the ringed coloration of the coral snake.
Both king snakes and coral snake live in the Carolinas , but the king snake’s range also extends into areas without coral snakes.
The distribution of these two species allowed the Pfennigs and Harcombe to test a key prediction of the mimicry hypothesis.
Mimicry should protect the king snake from predators, but only in regions where coral snakes live.
Predators in non–coral snake areas should attack king snakes more frequently than predators that live in areas where coral snakes are present.
To test the mimicry hypothesis, Harcombe made hundreds of artificial snakes.
The experimental group had the red, black, and yellow ring pattern of king snakes.
The control group had plain, brown coloring.
Equal numbers of both types were placed at field sites, including areas where coral snakes are absent.
After four weeks, the scientists retrieved the fake snakes and counted bite or claw marks.
Foxes, coyotes, raccoons, and black bears attacked snake models.
The data fit the predictions of the mimicry hypothesis.
The ringed snakes were attacked by predators less frequently than the brown snakes only within the geographic range of the coral snakes.
The snake mimicry experiment provides an example of how scientists design experiments to test the effect of one variable by canceling out the effects of unwanted variables.
The design is called a controlled experiment.
An experimental group (artificial king snakes) is compared with a control group (artificial brown snakes).
The experimental and control groups differ only in the one factor the experiment is designed to test—the effect of the snake’s coloration on the behavior of predators.
The brown artificial snakes allowed the scientists to rule out such variables as predator density and temperature as possible determinants of number of predator attacks.
Scientists do not control the experimental environment by keeping all variables constant.
Researchers usually “control” unwanted variables, not by eliminating them but by canceling their effects using control groups.
Let’s look at the nature of science.
There are limitations to the kinds of questions that science can address.
These limits are set by science’s requirements that hypotheses are testable and falsifiable and that observations and experimental results be repeatable.
The limitations of science are set by its naturalism.
Science seeks natural causes for natural phenomena.
Science cannot support or falsify supernatural explanations, which are outside the bounds of science.
Everyday use of the term theory implies an untested speculation.
The term theory has a very different meaning in science.
A scientific theory is much broader in scope than a hypothesis.
This is a hypothesis: “Mimicking poisonous snakes is an adaptation that protects nonpoisonous snakes from predators.”
This is a theory: “Evolutionary adaptations evolve by natural selection.”
A theory is general enough to generate many new, specific hypotheses that can be tested.
Compared to any one hypothesis, a theory is generally supported by a much more massive body of evidence.
The theories that become widely adopted in science (such as the theory of adaptation by natural selection) explain many observations and are supported by a great deal of evidence.
In spite of the body of evidence supporting a widely accepted theory, scientists may have to modify or reject theories when new evidence is found.
As an example, the five-kingdom theory of biological diversity eroded as new molecular methods made it possible to test some of the hypotheses about the relationships between living organisms.
Scientists may construct models in the form of diagrams, graphs, computer programs, or mathematical equations.
Models may range from lifelike representations to symbolic schematics.
Science is an intensely social activity.
Most scientists work in teams, which often include graduate and undergraduate students.
Both cooperation and competition characterize scientific culture.
Scientists attempt to confirm each other’s observations and may repeat experiments.
They share information through publications, seminars, meetings, and personal communication.
Scientists may be very competitive when converging on the same research question.
Science as a whole is embedded in the culture of its times.
For example, recent increases in the proportion of women in biology have had an impact on the research being performed.
For instance, there has been a switch in focus in studies of the mating behavior of animals from competition among males for access to females to the role that females play in choosing mates.
Recent research has revealed that females prefer bright coloration that “advertises” a male’s vigorous health, a behavior that enhances a female’s probability of having healthy offspring.
Some philosophers of science argue that scientists are so influenced by cultural and political values that science is no more objective than other ways of “knowing nature.”
At the other extreme are those who view scientific theories as though they were natural laws.
The reality of science is somewhere in between.
The cultural milieu affects scientific fashion, but need for repeatability in observation and hypothesis testing distinguishes science from other fields.
If there is “truth” in science, it is based on a preponderance of the available evidence.
Science and technology are functions of society.
Although science and technology may employ similar inquiry patterns, their basic goals differ.
The goal of science is to understand natural phenomena.
Technology applies scientific knowledge for some specific purpose.
Technology results from scientific discoveries applied to the development of goods and services.
Scientists put new technology to work in their research.
Science and technology are interdependent.
The discovery of the structure of DNA by Watson and Crick sparked an explosion of scientific activity.
These discoveries made it possible to manipulate DNA, enabling genetic technologists to transplant foreign genes into microorganisms and mass-produce valuable products.
DNA technology and biotechnology have revolutionized the pharmaceutical industry.
They have had an important impact on agriculture and the legal profession.
The direction that technology takes depends less on science than it does on the needs of humans and the values of society.
Debates about technology center more on “should we do it” than “can we do it.”
With advances in technology come difficult choices, informed as much by politics, economics, and cultural values as by science.
Scientists should educate politicians, bureaucrats, corporate leaders, and voters about how science works and about the potential benefits and hazards of specific technologies.

Concept 1.6 A set of themes connects the concepts of biology

In some ways, biology is the most demanding of all sciences, partly because living systems are so complex and partly because biology is a multidisciplinary science that requires knowledge of chemistry, physics, and mathematics.
Biology is also the science most connected to the humanities and social sciences.

Chapter 16 – Molecular Basis of Inheritance

Chapter 16 Molecular Basis of Inheritance

Objectives

DNA as the Genetic Material
1.	Explain why researchers originally thought protein was the genetic material.
2.	Summarize the experiments performed by the following scientists that provided evidence that DNA is the genetic material: a. Frederick Griffith b. Oswald Avery, Maclyn McCarty, and Colin MacLeod c. Alfred Hershey and Martha Chase d. Erwin Chargaff
3.	Explain how Watson and Crick deduced the structure of DNA and describe the evidence they used. Explain the significance of the research of Rosalind Franklin.
4.	Describe the structure of DNA. Explain the base-pairing rule and describe its significance.

	DNA Replication and Repair
5.	Describe the semiconservative model of replication and the significance of the experiments of Matthew Meselson and Franklin Stahl.
6.	Describe the process of DNA replication, including the role of the origins of replication and replication forks.
7.	Explain the role of DNA polymerases in replication.
8.	Explain what energy source drives the polymerization of DNA.
9.	Define antiparallel and explain why continuous synthesis of both DNA strands is not possible.
10.	Distinguish between the leading strand and the lagging strand.
11.	Explain how the lagging strand is synthesized even though DNA polymerase can add nucleotides only to the 39 end. Describe the significance of Okazaki fragments.
12.	Explain the roles of DNA ligase, primer, primase, helicase, topoisomerase, and single-strand binding proteins.
13.	Explain why an analogy can be made comparing DNA replication to a locomotive made of DNA polymerase moving along a railroad track of DNA.
14.	Explain the roles of DNA polymerase, mismatch repair enzymes, and nuclease in DNA proofreading and repair.
15.	Describe the structure and function of telomeres.
16.	Explain the possible significance of telomerase in germ cells and cancerous cell.

BACK

Chapter 17 AP Objectives

Chapter 17 From Gene to Protein

Objectives

The Connection Between Genes and Proteins
1.	Explain why dwarf peas have shorter stems than tall varieties.
2.	Explain the reasoning that led Archibald Garrod to first suggest that genes dictate phenotypes through enzymes.
3.	Describe Beadle and Tatum’s experiments with Neurospora and explain the contribution they made to our understanding of how genes control metabolism.
4.	Distinguish between the “one geneÐone enzyme” hypothesis and the “one geneÐone polypeptide” hypothesis and explain why the original hypothesis was changed.
5.	Explain how RNA differs from DNA.
6.	Briefly explain how information flows from gene to protein.
7.	Distinguish between transcription and translation.
8.	Compare where transcription and translation occur in prokaryotes and in eukaryotes.
9.	Define codon and explain the relationship between the linear sequence of codons on mRNA and the linear sequence of amino acids in a polypeptide.
10.	Explain the early techniques used to identify what amino acids are specified by the triplets UUU, AAA, GGG, and CCC.
11.	Explain why polypeptides begin with methionine when they are synthesized.
12.	Explain what it means to say that the genetic code is redundant and unambiguous.
13.	Explain the significance of the reading frame during translation.
14.	Explain the evolutionary significance of a nearly universal genetic code.

	The Synthesis and Processing of RNA
15.	Explain how RNA polymerase recognizes where transcription should begin. Describe the promoter, the terminator, and the transcription unit.
16.	Explain the general process of transcription, including the three major steps of initiation, elongation, and termination.
17.	Explain how RNA is modified after transcription in eukaryotic cells.
18.	Define and explain the role of ribozyme.
19.	Describe the functional and evolutionary significance of introns.

	The Synthesis of Protein
20.	Describe the structure and functions of tRNA.
21.	Explain the significance of wobble.
22.	Explain how tRNA is joined to the appropriate amino acid.
23.	Describe the structure and functions of ribosomes.
24.	Describe the process of translation (including initiation, elongation, and termination) and explain which enzymes, protein factors, and energy sources are needed for each stage.
25.	Describe the significance of polyribosomes.
26.	Explain what determines the primary structure of a protein and describe how a polypeptide must be modified before it becomes fully functional.
27.	Describe what determines whether a ribosome will be free in the cytosol or attached to the rough endoplasmic reticulum.
28.	Describe two properties of RNA that allow it to perform so many different functions.
29.	Compare protein synthesis in prokaryotes and in eukaryotes.
30.	Define point mutations. Distinguish between base-pair substitutions and base-pair insertions. Give examples of each and note the significance of such changes.
31.	Describe several examples of mutagens and explain how they cause mutations.
32.	Describe the historical evolution of the concept of a gene.

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Protein Synthesis Quiz

Name:

DNA & Protein Synthesis

True/False

Indicate whether the sentence or statement is true or false.

When a tRNA anticodon binds to an mRNA codon, the amino acid detaches from the tRNA molecule and attaches to the end of a growing protein chain.

Only ribosomal RNA plays a role in translation.

During DNA replication, the molecule unzips and the exposed DNA nucleotides pair with other

specific nucleotides present in the nucleus

Humans pass exact copies of their DNA to their offspring.

Watson and Crick proposed a model of DNA

Amino acids are linked together by hydrogen bonds.

During transcription, the information on a DNA molecule is “rewritten” into an mRNA molecule.

All codons encode amino acids.

Multiple Choice

Identify the letter of the choice that best completes the statement or answers the question.

Purines and pyrimidines are

a.	bases found in amino acids.
b.	able to replace phosphate groups from defective DNA.
c.	names of specific types of DNA molecules.
d.	bases found in nucleotides.

10.

Chargaff’s rules, or the base-pairing rules, state that in DNA

a.	the amount of adenine equals the amount of thymine.
b.	the amount of guanine equals the amount of cytosine.
c.	the amount of guanine equals the amount of thymine.
d.	Both a and b

11.

ATTG : TAAC ::

a.	AAAT : TTTG	c.	GTCC : CAGG
b.	TCGG : AGAT	d.	CGAA : TGCG

12.

Which of the following types of RNA carries instructions for making proteins?

a.	mRNA	c.	tRNA
b.	rRNA	d.	All of the above

13.

Which of the following is not found in DNA?

a.	adenine	c.	uracil
b.	cytosine	d.	None of the above

14.

Suppose that you are given a polypeptide sequence containing the following sequence of amino acids: tyrosine, proline, aspartic acid, isoleucine, and cysteine. Use the portion of the genetic code given in the table below to determine the DNA sequence that codes for this polypeptide sequence.

mRNA	Amino acid
UAU, UAC	tyrosine
CCU, CCC, CCA, CCG	proline
GAU, GAC	aspartic acis
AUU, AUC, AUA	isoleucine
UGU, UGC	cysteine

a.	AUGGGUCUAUAUACG	c.	GCAAACTCGCGCGTA
b.	ATGGGTCTATATACG	d.	ATAGGGCTTTAAACA

15.

In order for protein synthesis to occur, mRNA must migrate to the

a.	ribosomes.	c.	RNA polymerase.
b.	lac operon.	d.	heterochromatin.

16.

After the primary structure of a protein has been completed

a.	the codons and anticodons unite.
b.	an enzyme attaches adjacent amino acids to each other to form a chain.
c.	the protein folds into the secondary and tertiary structures.
d.	the tRNA molecules remain attached until the protein is secreted from the cell.

17.

Which of the following is not part of a molecule of DNA?

a.	deoxyribose	c.	phosphate
b.	nitrogenous base	d.	ribose

18.

During replication in a molecule of DNA, one separation likely to occur is between

a.	cytosine and guanine	c.	ribose and adenine
b.	phosphate and deoxyribose	d.	uracil and thymine

19.

A gene may be described as

a.	a sequence of amino acids.
b.	special proteins found in chromosomes.
c.	a sequence of nucleotides that controls the production of a certain protein.
d.	a sequence of nucleotides coding for the production of starches and sugars.

20.

The synthesis of a new double strand of DNA begins when the two strand of the original DNA helix

a.	‘unzip’.	c.	attract nitrogenous bases.
b.	act as a template.	d.	destroy a genetic code.

21.

Genes(DNA) affect cell structure and function by directing the synthesis of

a.	nucleic acids	c.	nucleotides
b.	hereditary traits	d.	proteins

22.

Protein molecules are made up of

a.	fats	c.	lipids
b.	nucleotides	d.	amino acids

23.

During, DNA replication, DNA

a.	converts to RNA	c.	joins mRNA
b.	joins tRNA	d.	strands separate

24.

Which is not true about proteins?

a.	They control biochemical pathways within the cell.
b.	They direct the synthesis of lipids.
c.	They are composed of sugars.
d.	They take responsibility for cell movement.

25.

Molecules of DNA are composed of long chains of

a.	amino acids.	c.	monosaccharides.
b.	fatty acids.	d.	nucleotides.

26.

Watson and Crick were the first scientists to state that DNA

a.	contains phosphate groups	c.	has four nitrogen bases
b.	undergoes transcription	d.	has a double helix shape

27.

The two chains of a DNA molecule are connected by

a.	nitrogen bonds	c.	bases
b.	relatively weak chemical bonds	d.	nucleotides

28.

All nucleotide molecules contain the same kind of

a.	ribose sugar	c.	pyrimidine
b.	purine	d.	phosphate group

29.

After DNA replication, the two DNA molecules that are made

a.	are complementary.	c.	must replicate again.
b.	are identical.	d.	cannot replicate again.

30.

Sixty-four codons for 20 amino acids requires that

a.	some amino acids lack codons
b.	some amino acids have more than one codon
c.	all amino acids have two codons
d.	none of the above

31.

Which of the following combines with amino acids

a.	DNA	c.	tRNA
b.	mRNA	d.	B and C

32.

rRNA has a function in

a.	synthesizing DNA.	c.	forming ribosomes.
b.	synthesizing mRNA.	d.	transferring amino acids to ribosomes.

33.

The DNA code consists of sequences of nucleotides arranged in groups of

a.	variable number	c.	threes
b.	twos	d.	fours

34.

Unlike mRNA, the DNA molecule is

a.	double-stranded	c.	like a ladder
b.	single-stranded	d.	both A and C

35.

The number of bases in a row in a gene that codes a protein composed of 200 amino acids is

a.	200	c.	600
b.	400	d.	800

36.

A DNA molecule unzips during

a.	replication	c.	translation
b.	transcription	d.	both A and B

37.

A DNA chain has the following sequence of bases, TAG. The corresponding messenger RNA

chain should have the sequence

a.	ATC	c.	ATG
b.	UTC	d.	AUC

38.

Unlike DNA, RNA

a.	contains deoxyribose.	c.	contains thymine.
b.	is double stranded.	d.	contains uracil.

39.

Which molecule contains deoxyribose

a.	DNA	c.	tRNA
b.	mRNA	d.	both B and C

40.

Each combination of three nitrogenous bases on messenger RNA forms a (an)

a.	anticodon.	c.	enzyme.
b.	codon.	d.	nuclei acid.

41.

In RNA, uracil is complementary to:

a.	guanine	c.	thymine
b.	adenine	d.	cytosine

42.

Once a molecule of transfer RNA has released its amino acid, the tRNA

a.	becomes attached to messenger RNA.
b.	becomes attached to ribosomal RNA.
c.	is destroyed as an individual molecule.
d.	moves away to pick up another amino acid.

43.

If the sequence of bases in a segment of a DNA strand were cytosine, guanine, adenine, thymine, adenine, then the sequence in a complimentary strand of newly-made mRNA would be

a.	cytosine, uracil, adenine, guanine, uracil	c.	uracil, adenine, cytosine, uracil, guanine
b.	guanine, cytosine, uracil, adenine, uracil	d.	cytosine, guanine, uracil, uracil, adenine

44.

Which sugar is present in RNA

a.	glucose	c.	ribose
b.	sucrose	d.	deoxyribose

45.

RNA differs from DNA, in that RNA

a.	is single-stranded.	c.	contains the nitrogen base uracil.
b.	contains a different sugar molecule.	d.	All of the above are correct.

Chapter 11 – Cell Communication – Lecture Outline

Chapter 11 Cell Communication Lecture Outline

Overview

· Cell-to-cell communication is absolutely essential for multicellular organisms.

° Cells must communicate to coordinate their activities.

· Communication between cells is also important for many unicellular organisms.

· Biologists have discovered universal mechanisms of cellular regulation involving the same small set of cell-signaling mechanisms.

° The ubiquity of these mechanisms provides additional evidence for the evolutionary relatedness of all life.

· Cells most often communicate by chemical signals, although signals may take other forms.

A. An Overview of Cell Signaling

· What messages are passed from cell to cell? How do cells respond to these messages?

· We will first consider communication in microbes, to gain insight into the evolution of cell signaling.

1. Cell signaling evolved early in the history of life.

· One topic of cell “conversation” is sex.

· Saccharomyces cerevisiae, the yeast of bread, wine, and beer, identifies potential mates by chemical signaling.

° There are two sexes, a and a, each of which secretes a specific signaling molecule, a factor and a factor, respectively.

° These factors each bind to receptor proteins on the other mating type.

· Once the mating factors have bound to the receptors, the two cells grow toward each other and undergo other cellular changes.

· The two cells fuse, or mate, to form an a/a cell containing the genes of both cells.

· The process by which a signal on a cell’s surface is converted into a specific cellular response is a series of steps called a signal-transduction pathway.

° The molecular details of these pathways are strikingly similar in yeast and animal cells, even though their last common ancestor lived more than a billion years ago.

° Signaling systems of bacteria and plants also share similarities.

· These similarities suggest that ancestral signaling molecules evolved long ago in prokaryotes and have since been adopted for new uses by single-celled eukaryotes and multicellular descendents.

2. Communicating cells may be close together or far apart.

· Multicellular organisms release signaling molecules that target other cells.

· Cells may communicate by direct contact.

° Both animals and plants have cell junctions that connect to the cytoplasm of adjacent cells.

° Signaling substances dissolved in the cytosol can pass freely between adjacent cells.

° Animal cells can communicate by direct contact between membrane-bound cell surface molecules.

° Such cell-cell recognition is important to such processes as embryonic development and the immune response.

· In other cases, messenger molecules are secreted by the signaling cell.

° Some transmitting cells release local regulators that influence cells in the local vicinity.

° One class of local regulators in animals, growth factors, includes compounds that stimulate nearby target cells to grow and multiply.

° This is an example of paracrine signaling, which occurs when numerous cells simultaneously receive and respond to growth factors produced by a single cell in their vicinity.

· In synaptic signaling, a nerve cell produces a neurotransmitter that diffuses across a synapse to a single cell that is almost touching the sender.

° The neurotransmitter stimulates the target cell.

° The transmission of a signal through the nervous system can also be considered an example of long-distance signaling.

· Local signaling in plants is not well understood. Because of their cell walls, plants must have different mechanisms from animals.

· Plants and animals use hormones for long-distance signaling.

° In animals, specialized endocrine cells release hormones into the circulatory system, by which they travel to target cells in other parts of the body.

° Plant hormones, called growth regulators, may travel in vessels but more often travel from cell to cell or move through air by diffusion.

· Hormones and local regulators range widely in size and type.

° The plant hormone ethylene (C2H4), which promotes fruit ripening and regulates growth, is a hydrocarbon of only six atoms, capable of passing through cell walls.

° Insulin, which regulates blood sugar levels in mammals, is a protein with thousands of atoms.

· What happens when a cell encounters a signal?

° The signal must be recognized by a specific receptor molecule, and the information it carries must be changed into another form, or transduced, inside the cell before the cell can respond.

3. The three stages of cell signaling are reception, transduction, and response.

· E. W. Sutherland and his colleagues pioneered our understanding of cell signaling.

° Their work investigated how the animal hormone epinephrine stimulates breakdown of the storage polysaccharide glycogen in liver and skeletal muscle.

° Breakdown of glycogen releases glucose derivatives that can be used for fuel in glycolysis or released as glucose in the blood for fuel elsewhere.

° Thus one effect of epinephrine, which is released from the adrenal gland during times of physical or mental stress, is mobilization of fuel reserves.

· Sutherland’s research team discovered that epinephrine activated a cytosolic enzyme, glycogen phosphorylase.

° However, epinephrine did not activate the phosphorylase directly in vitro but could only act via intact cells.

° Therefore, there must be an intermediate step or steps occurring inside the cell.

° The plasma membrane must be involved in transmitting the epinephrine signal.

· The process involves three stages: reception, transduction, and response.

° In reception, a chemical signal binds to a cellular protein, typically at the cell’s surface or inside the cell.

° In transduction, binding leads to a change in the receptor that triggers a series of changes in a series of different molecules along a signal-transduction pathway. The molecules in the pathway are called relay molecules.

° In response, the transduced signal triggers a specific cellular activity.

B. Signal Reception and the Initiation of Transduction

1. A signal molecule binds to a receptor protein, causing the protein to change shape.

· The cell targeted by a particular chemical signal has a receptor protein on or in the target cell that recognizes the signal molecule.

° Recognition occurs when the signal binds to a specific site on the receptor that is complementary in shape to the signal.

· The signal molecule behaves as a ligand, a small molecule that binds with specificity to a larger molecule.

· Ligand binding causes the receptor protein to undergo a change in shape.

· This may activate the receptor so that it can interact with other molecules.

° For other receptors, this causes aggregation of receptor molecules, leading to further molecular events inside the cell.

· Most signal receptors are plasma membrane proteins, whose ligands are large water-soluble molecules that are too large to cross the plasma membrane.

2. Some receptor proteins are intracellular.

· Some signal receptors are dissolved in the cytosol or nucleus of target cells.

° To reach these receptors, the signals pass through the target cell’s plasma membrane.

° Such chemical messengers are either hydrophobic enough or small enough to cross the phospholipid interior of the plasma membrane.

· Hydrophobic messengers include the steroid and thyroid hormones of animals.

· Nitric oxide (NO) is a gas whose small size allows it to pass between membrane phospholipids.

· Testosterone is secreted by the testis and travels through the blood to enter cells throughout the body.

° The cytosol of target cells contains receptor molecules that bind testosterone, activating the receptor.

° These activated proteins enter the nucleus and turn on specific genes that control male sex characteristics.

· How does the activated hormone-receptor complex turn on genes?

· These activated proteins act as transcription factors.

· Transcription factors control which genes are turned on—that is, which genes are transcribed into messenger RNA.

· mRNA molecules leave the nucleus and carry information that directs the synthesis (translation) of specific proteins at the ribosome.

· Other intracellular receptors (such as thyroid hormone receptors) are found in the nucleus and bind to the signal molecules there.

3. Most signal receptors are plasma membrane proteins.

· Most signal molecules are water-soluble and too large to pass through the plasma membrane.

· They influence cell activities by binding to receptor proteins on the plasma membrane.

° Binding leads to changes in the shape of the receptor or to the aggregation of receptors.

° These cause changes in the intracellular environment.

· There are three major types of membrane receptors: G-protein-linked receptors, receptor tyrosine kinases, and ion-channel receptors.

· A G-protein-linked receptor consists of a receptor protein associated with a G protein on the cytoplasmic side.

° Seven alpha helices span the membrane.

° G-protein-linked receptors bind many different signal molecules, including yeast mating factors, epinephrine and many other hormones, and neurotransmitters.

· The G protein acts as an on/off switch.

° If GDP is bound to the G protein, the G protein is inactive.

° When the appropriate signal molecule binds to the extracellular side of the receptor, the G protein binds GTP (instead of GDP) and becomes active.

° The activated G protein dissociates from the receptor and diffuses along the membrane, where it binds to an enzyme, altering its activity.

° The activated enzyme triggers the next step in a pathway leading to a cellular response.

· The G protein can also act as a GTPase enzyme to hydrolyze GTP to GDP.

° This change turns the G protein off.

· Now inactive, the G protein leaves the enzyme, which returns to its original state.

· The whole system can be shut down quickly when the extracellular signal molecule is no longer present.

· G-protein receptor systems are extremely widespread and diverse in their functions.

° They play important roles during embryonic development.

° Vision and smell in humans depend on these proteins.

· Similarities among G proteins and G-protein-linked receptors of modern organisms suggest that this signaling system evolved very early.

· Several human diseases involve G-protein systems.

° Bacterial infections causing cholera and botulism interfere with G-protein function.

· The tyrosine-kinase receptor system is especially effective when the cell needs to trigger several signal transduction pathways and cellular responses at once.

° This system helps the cell regulate and coordinate many aspects of cell growth and reproduction.

· The tyrosine-kinase receptor belongs to a major class of plasma membrane receptors that have enzymatic activity.

° A kinase is an enzyme that catalyzes the transfer of phosphate groups.

° The cytoplasmic side of these receptors functions as a tyrosine kinase, transferring a phosphate group from ATP to tyrosine on a substrate protein.

· An individual tyrosine-kinase receptor consists of several parts:

° An extracellular signal-binding site.

° A single alpha helix spanning the membrane.

° An intracellular tail with several tyrosines.

· The signal molecule binds to an individual receptor.

° Ligands bind to two receptors, causing the two receptors to aggregate and form a dimer.

· This dimerization activates the tyrosine-kinase section of the receptors, each of which then adds phosphate from ATP to the tyrosine tail of the other polypeptide.

· The fully activated receptor proteins activate a variety of specific relay proteins that bind to specific phosphorylated tyrosine molecules.

° One tyrosine-kinase receptor dimer may activate ten or more different intracellular proteins simultaneously.

° These activated relay proteins trigger many different transduction pathways and responses.

· A ligand-gated ion channel is a type of membrane receptor that can act as a gate when the receptor changes shape.

· When a signal molecule binds as a ligand to the receptor protein, the gate opens to allow the flow of specific ions, such as Na+ or Ca2+, through a channel in the receptor.

° Binding by a ligand to the extracellular side changes the protein’s shape and opens the channel.

° When the ligand dissociates from the receptor protein, the channel closes.

· The change in ion concentration within the cell may directly affect the activity of the cell.

· Ligand-gated ion channels are very important in the nervous system.

° For example, neurotransmitter molecules released at a synapse between two neurons bind as ligands to ion channels on the receiving cell, causing the channels to open.

° Ions flow in and trigger an electrical signal that propagates down the length of the receiving cell.

· Some gated ion channels respond to electrical signals, instead of ligands.

C. Signal-Transduction Pathways

· The transduction stage of signaling is usually a multistep pathway.

· These pathways often greatly amplify the signal.

° If some molecules in a pathway transmit a signal to multiple molecules of the next component in the series, the result can be large numbers of activated molecules at the end of the pathway.

· A small number of signal molecules can produce a large cellular response.

· Also, multistep pathways provide more opportunities for coordination and regulation than do simpler systems.

1. Pathways relay signals from receptors to cellular responses.

· Signal-transduction pathways act like falling dominoes.

° The signal-activated receptor activates another protein, which activates another, and so on, until the protein that produces the final cellular response is activated.

· The relay molecules that relay a signal from receptor to response are mostly proteins.

° The interaction of proteins is a major theme of cell signaling.

° Protein interaction is a unifying theme of all cellular regulation.

· The original signal molecule is not passed along the pathway and may not even enter the cell.

° It passes on information.

° At each step, the signal is transduced into a different form, often by a conformational change in a protein.

° The conformational change is often brought about by phosphorylation.

2. Protein phosphorylation, a common mode of regulation in cells, is a major mechanism of signal transduction.

· The phosphorylation of proteins by a specific enzyme (a protein kinase) is a widespread cellular mechanism for regulating protein activity.

° Most protein kinases act on other substrate proteins, unlike tyrosine kinases that act on themselves.

· Most phosphorylation occurs at either serine or threonine amino acids of the substrate protein (unlike tyrosine phosphorylation in tyrosine kinases).

· Many of the relay molecules in a signal-transduction pathway are protein kinases that act on other protein kinases to create a “phosphorylation cascade.”

· Each protein phosphorylation leads to a conformational change because of the interaction between the newly added phosphate group and charged or polar amino acids on the protein.

· Phosphorylation of a protein typically converts it from an inactive form to an active form.

° Rarely, phosphorylation inactivates protein activity.

· A single cell may have hundreds of different protein kinases, each specific for a different substrate protein.

° Fully 2% of our genes are thought to code for protein kinases.

° Together, they regulate a large proportion of the thousands of cell proteins.

· Abnormal activity of protein kinases can cause abnormal cell growth and may contribute to the development of cancer.

· The responsibility for turning off a signal-transduction pathway belongs to protein phosphatases.

° These enzymes rapidly remove phosphate groups from proteins, a process called dephosphorylation.

° Phosphatases also make the protein kinases available for reuse, enabling the cell to respond again to a signal.

· At any given moment, the activity of a protein regulated by phosphorylation depends on the balance of active kinase molecules and active phosphatase molecules.

· When the extracellular signal molecule is absent, active phosphatase molecules predominate, and the signaling pathway and cellular response are shut down.

· The phosphorylation/dephosphorylation system acts as a molecular switch in the cell, turning activities on and off as required.

3. Certain signal molecules and ions are key components of signaling pathways (second messengers).

· Many signaling pathways involve small, water-soluble, nonprotein molecules or ions called second messengers.

° These molecules rapidly diffuse throughout the cell.

· Second messengers participate in pathways initiated by both G-protein-linked receptors and tyrosine-kinase receptors.

° Two of the most widely used second messengers are cyclic AMP and Ca2+.

· Once Sutherland knew that epinephrine caused glycogen breakdown without entering the cell, he looked for a second messenger inside the cell.

· Binding by epinephrine leads to increases in the cytosolic concentration of cyclic AMP, or cAMP.

° This occurs because the activated receptor activates adenylyl cyclase, which converts ATP to cAMP.

° The normal cellular concentration of cAMP can be boosted twentyfold within seconds.

° cAMP is short-lived, as phosphodiesterase converts it to AMP.

° Another surge of epinephrine is needed to reboost the cytosolic concentration of cAMP.

· Caffeine-containing beverages such as coffee provide an artificial way to keep the body alert.

° Caffeine blocks the conversion of cAMP to AMP, maintaining the system in a state of activation in the absence of epinephrine.

· Many hormones and other signal molecules trigger the formation of cAMP.

° G-protein-linked receptors, G proteins, and protein kinases are other components of cAMP pathways.

° cAMP diffuses through the cell and activates a serine/threonine kinase called protein kinase A.

° The activated kinase phosphorylates various other proteins.

· Regulation of cell metabolism is also provided by G-protein systems that inhibit adenylyl cyclase.

° These use a different signal molecule to activate a different receptor that activates an inhibitory G protein.

· Certain microbes cause disease by disrupting G-protein signaling pathways.

° The cholera bacterium, Vibrio cholerae, may be present in water contaminated with human feces.

° This bacterium colonizes the small intestine and produces a toxin that modifies a G protein that regulates salt and water secretion.

° The modified G protein is unable to hydrolyze GTP to GDP and remains stuck in its active form, continuously stimulating adenylyl cyclase to make cAMP.

° The resulting high concentration of cAMP causes the intestinal cells to secrete large amounts of water and salts into the intestines, leading to profuse diarrhea and death from loss of water and salts.

· Treatments for certain human conditions involve signaling pathways.

° One pathway uses cyclic GMP, or cGMP, as a signaling molecule. Its effects include the relaxation of smooth muscle cells in artery walls.

° A compound was developed to treat chest pains. This compound inhibits the hydrolysis of cGMP to GMP, prolonging the signal and increasing blood flow to the heart muscle.

° Under the trade name Viagra, this compound is now widely used as a treatment for erectile dysfunction. Viagra causes dilation of blood vessels, allowing increased blood flow to the penis.

· Many signal molecules in animals induce responses in their target cells via signal-transduction pathways that increase the cytosolic concentration of Ca2+.

° In animal cells, increases in Ca2+ may cause contraction of muscle cells, secretion of certain substances, and cell division.

° In plant cells, increases in Ca2+ trigger responses such as the pathway for greening in response to light.

· Cells use Ca2+ as a second messenger in both G-protein pathways and tyrosine-kinase pathways.

· The Ca2+ concentration in the cytosol is typically much lower than that outside the cell, often by a factor of 10,000 or more.

° Various protein pumps transport Ca2+ outside the cell or into the endoplasmic reticulum or other organelles.

° As a result, the concentration of Ca2+ in the ER is usually much higher than the concentration in the cytosol.

· Because cytosolic Ca2+ is so low, small changes in the absolute numbers of ions causes a relatively large percentage change in Ca2+ concentration.

· Signal-transduction pathways trigger the release of Ca2+ from the cell’s ER.

· The pathways leading to release involve still other second messengers, diacylglycerol (DAG) and inositol trisphosphate (IP3).

° DAG and IP3 are created when a phospholipase cleaves membrane phospholipid PIP2.

° The phospholipase may be activated by a G protein or by a tyrosine-kinase receptor.

° IP3 activates a gated-calcium channel, releasing Ca2+ from the ER.

· Calcium ions activate the next protein in a signal-transduction pathway.

D. Cellular Responses to Signals

1. In response to a signal, a cell may regulate activities in the cytoplasm or transcription in the nucleus.

· Ultimately, a signal-transduction pathway leads to the regulation of one or more cellular activities.

° This may be the opening or closing of an ion channel or a change in cell metabolism.

° For example, epinephrine helps regulate cellular energy metabolism by activating enzymes that catalyze the breakdown of glycogen.

· The stimulation of glycogen breakdown by epinephrine involves a G-protein-linked receptor, a G protein, adenylyl cyclase, cAMP, and several protein kinases before glycogen phosphorylase is activated.

· Other signaling pathways do not regulate the activity of enzymes but the synthesis of enzymes or other proteins.

· Activated receptors may act as transcription factors that turn specific genes on or off in the nucleus.

2. Elaborate pathways amplify and specify the cell’s response to signals.

· Signaling pathways with multiple steps have two benefits.

They amplify the response to a signal.

They contribute to the specificity of the response.

· At each catalytic step in a cascade, the number of activated products is much greater than in the preceding step.

° In the epinephrine-triggered pathway, binding by a small number of epinephrine molecules can lead to the release of hundreds of millions of glucose molecules.

· Various types of cells may receive the same signal but produce very different responses.

° For example, epinephrine triggers liver or striated muscle cells to break down glycogen, but stimulates cardiac muscle cells to contract, leading to a rapid heartbeat.

· The explanation for this specificity is that different kinds of cells have different collections of proteins.

° The response of a particular cell to a signal depends on its particular collection of receptor proteins, relay proteins, and proteins needed to carry out the response.

° Two cells that respond differently to the same signal differ in one or more of the proteins that handle and respond to the signal.

· A signal may trigger a single pathway in one cell but trigger a branched pathway in another.

· Two pathways may converge to modulate a single response.

· Branching of pathways and interactions between pathways are important for regulating and coordinating a cell’s response to incoming information.

· Rather than relying on diffusion of large relay molecules such as proteins, many signal pathways are linked together physically by scaffolding proteins.

° Scaffolding proteins may themselves be relay proteins to which several other relay proteins attach.

° This hardwiring enhances the speed, accuracy, and efficiency of signal transfer between cells.

· The importance of relay proteins that serve as branch or intersection points in signaling pathways is underscored when these proteins are defective or missing.

° The inherited disorder Wiskott-Aldrich syndrome (WAS) is caused by the absence of a single relay protein.

° Symptoms include abnormal bleeding, eczema, and a predisposition to infections and leukemia, due largely to the absence of the protein in the cells of the immune system.

° The WAS protein is located just beneath the cell surface, where it interacts with the microfilaments of the cytoskeleton and with several signaling pathways, including those that regulate immune cell proliferation.

° When the WAS protein is absent, the cytoskeleton is not properly organized and signaling pathways are disrupted.

· As important as activating mechanisms are inactivation mechanisms.

° For a cell to remain alert and capable of responding to incoming signals, each molecular change in its signaling pathways must last only a short time.

° If signaling pathway components become locked into one state, whether active or inactive, the proper function of the cell can be disrupted.

° Binding of signal molecules to receptors must be reversible, allowing the receptors to return to their inactive state when the signal is released.

° Similarly, activated signals (cAMP and phosphorylated proteins) must be inactivated by appropriate enzymes to prepare the cell for a fresh signal.