1. Recognize a hydrogen bond and atoms or groups of atoms that can take part in forming a hydrogen bond.

Hydrogen, Oxygen, Water, or any polar compound

2. Define the ion product for water! Given any hydroxide ion concentration, determine the hydrogen ion concentration and visa versa.

Define pH. Given any hydrogen ion concentration, determine the pH and visa versa

pH=pKa+log[a-]/[ha]

pH is the negative log 10 of the hydrogen ion concentration expressed in mol/L

Acids are compounds that doante protons.

Bases are compounds that accept protons.

Recognize the acids produced by the body during metabolism and be able to state the predominant form at pH = 7.4 (ic or ate, ammonium or ammonia).

Phosphoric acid, sulfuric acid, lactic acid, hydrochloric acid, and the ketone bodies acetoacetic acid and betahyroxybutyric acid.

Strong acids dissaccociate completely

No

Given a weak acid, be able to draw the equation for its dissociation and label the conjugate base (salt of the acid). Be able to define the Ka for the acid. Be able to write the Henderson-Hasselbalch equation for an acid.

Ka is the equilibrium constant for the dissacociation of a weak acid. 

pH=pK+log10[a-]/[ha]

Define the term buffer! Name two factors that determine the effectiveness of the buffer! At what pH are buffers most effective?

Buffers consist of a wealk acid and its conjugate base.  They cause a solution to resist pH changes.  They are affected by pH and temperature.  They are only effective within 1 pH unit of their pKa.

What is the most important reason for maintaining a physiological pH?

 Be able to draw the equations that show how the bicarbonate buffer system works in blood! What is the respiratory compensation when the blood pH drops to 7.3? What is the respiratory compensation when the blood pH rises to 7.5?

Increased respiration gets rid of carbonic acid thus raising the pH. (Kaussumauls breathing)

 Regarding Di Abietes: Define Type 1 diabetes. With out insulin, what happens to the blood glucagon concentration? What happens to her blood glucose and ketone body levels (concentrations)?

Type I diabetes results from an inability to secrete insulin. 

Glucagon ???

Blood glucose levels rise since insulin stimulates storage of glucose as fat.  Ketone bodies are created as the liver unneccesarily mobilizes fatty acids from adipose tissue.  Ketoacidosis results.

 Regarding Di Abietes: Explain why an increase in a metabolic acid would cause the changes seen in PaCO₂ and serum bicarbonate. What would happen to the concentration of CO₂ and serum bicarbonate after the insulin injection?

As Ketoacidosis lowers blood pH Kaussumauls respiration increases breathing to remove carbonic acid from the bloodstream.

Serum bicarb is low as pH is low.

After insulin injection the concentration of CO2 and serum bicarb would rise.

Concerning Dennis Veere: If the pKa for acetylsalicylic acid to acetylsalicylate is 3.5, is aspirin a weak or strong acid?

Which form is prevalent in the stomach at a pH of 1?

Which form is prevalent in blood? Prove it using the Henderson-Hasselbalch equation.

Strong??

Acetylsalicylic acid in the stomach

Acetylsalicylate in the blood.

Regarding Percy Veere: Using the Henderson-Hasselbalch equation, explain the effect of breathing into a paper bag upon blood pH.

It recycles CO2 into the blood stream preventing the pH from being lowered.

Given a biological molecule, be able to name the functional groups.

Be able to tell if a biological molecule is oxidized or reduced.

Oxidized:  It could add some protons

Reduced: its full up on protons

What are the substrates for a reaction that forms an ester, a thioester, an amide, a phosphoester, and an acid anhydride? What are the products of a reaction that hydrolyzes an ester, a thioester, an amide, a phosphoester, and an acid anhydride?

acid+alchol=ester

acid+sulfhydryl=thioester

acid+amine=amide

phosphoric acid+alchol=phosphoester

acid+acid=anhydride

Be able to recognize a aldose and ketose.!

o--c-h aldose

o--c-c ketose

Given two compounds, be able to tell whether they are stereoisomers or epimers

Steroisomers: all variations of the same formula

Epimers: vary at only one carbon.

What is the difference between alpha- and beta-D-glucopyranose?

Mutorotation

alpha OH below

beta OH above

Compare glucuronate, gluconate, and sorbitol with glucose

Glucuronate and Gluconate or oxidized forms of glucose

Sorbitol is the reduced form of Glucose.

 Be able to identify alpha-O-, alpha-N-, beta-O- and beta-N-glycosidic bonds?

O bonds are from an OH group

N bonds are from and NH group

Alpha below the ring

Beta above the ring

Be able to identify the structure of a fatty acid. Be able to differentiate between Palmitic acid, Stearic acid, Oleic acid, a-Linolenic acid and Arachidonic acid.

methyl at one end carboxyl at the other

cabons in chain:conjugated bonds

stearic 18:0

oleic 18:1

alpha linoleic: 18:3

arachidonic: 20:4

Be able to use delta-numeric and omega nomenclature to identify the position of double bonds.

18:1 [4]  18 carbons n the acid chain: 1 double bond located at carbon 4-5  carbons numbered right to left.

Why is the length and saturation of the fatty acids in phospholipids important

increasing length increasing melting point

increasing conjugation decreasing melting point. 

Be able to recognize the names of and the structures of the phosphatidic acid, phosphatidylcholine, and lecithin.

What does the lyso in lysolecithin indicate?

Removal of the fatty acyl group

Be able to tell the difference between sphingomyelin and lecithin!

lecithin has glycerol backbone ch2-ch-ch2

sphingomyelin is atached to ceramide that conatins nitrogen.

One side of the rings is hydrophilic.  the other is phobic.

Compunds that have a single electron in an outer orbit and exist independently in solution.

hydroxide, nitrogen dioxide, superoxide

OH, NO2, O2-

Concerning Di Abetes, what two compounds were raised in her blood that caused acidosis? Where were they made? Which one was not measured by the nitroprusside reaction and why wasn't it measured?

acetoacetate and beta hydroxybutrate

made in the liver

acetoacetate can be meaused with the reducing sugar test

betahydroxybutrate lacks a ketone group so it is unreactive.

Concerning Di Abetes, given a basic solution containing adenosine monophosphate, glucose, fructose and galactose, which of these compounds will undergo a positive reducing sugar test? Why?

glucose, fructose and galactose all reduce. Adenisine monophosphate will not react since its sugar is bound.

enzymatic conversion of glucose to hydrogen peroxide

Concerning Lotta Topaigne, Given that the pKa for uric acid is 5.7 and that uric acid is 20 times less soluble than sodium urate, explain which is more likely to precipitate in the toe and which is more likely to precipitate in the kidney tubule

sodium urate preciptates in the toes

uric acid preciptates in the kidney tubules.

What is the approximate pKa for all alpha-amino groups and for all alpha-carboxyl groups? Are they charged at pH=7?

ALA

alanine

nonpolar, aliphatic

Arginine

charged, basic

aspargine

Polar uncharged

aspartate

charged, acid

cysteine

sulfur containing

forms disulfide bridges

glutamate

charged, acidic

glutamine

polar, uncharged

glycine

nonpolar, aliphatic

smallest

histidine

charged, basic

isoleucine

nonpolar, aliphatic, branched chain

leucine

nonpolar, aliphatic, branched chain

lysine

charged, basic

methionine

sulfur containing

phenylalanine

aromatic, non polar

proline

non polar, aliphatic, cyclic

serine

polar, uncharged

threonine

polar, uncharged

tryptophan

aromatic, polar

tyrosine

aromatic, polar

valine

non polar, aliphatic, branched chain

Be able to name the structures of all 20 amino acids. Be able to say which contain R-groups that are nonpolar, polar, or charged! Be able to predict which R groups should be soluble in water and which should not

[image]

Be able to recognize cysteine, cystine, a sulfhydryl group, and a disulfide bond. Which are more oxidized and which are more reduced?

cysteine has a sulfhydryl group.  when that is oxidized the two cysteines form a disulfide bridge and become cystine.

Be able to recognize a salt bond (electrostatic interaction).

Interactions between amino acid residues in a polypeptide chain. (1) Electro static interactions; (2) hydrogen bonds; (3) hydrophobic interactions; and (4) a disulfide bond.

[image]

Given any two amino acids, predict whether their R-groups could form a salt bond at pH = 7.4.

The charged groups can form isoelectric bonds.

What are the pKa's for the R-groups of aspartic acid, glutamic acid, histidine, lysine, and arginine?

Given the pH, predict whether the R-groups of the amino acids aspartic acid, glutamic acid, histidine, lysine, and arginine would be neutral or would carry a net negative or net positive charge.

Given the pH, predict whether the amino acids aspartic acid, glutamic acid, histidine, lysine, and arginine would be neutral or would carry a net negative or net positive charge.

Define the pI (the isoelectric point) for an amino acid.

Given any amino acid except cysteine serine, threonine and tyrosine, be able to predict the isoelectric point

Is the substitution of a glutamate for a valine [valine for a glutamate] in sickle cell hemoglobin a conservative replacement? What about the substitution of an aspartate for a glutamate?

nonconservative, glutamate charged, valine nonpolar.

Given the written sequence for a protein, be able to identify the amino-terminus, the carboxyl-terminus, and the R-groups for each residue.

Concerning Michael Sichel: To the extent covered in this chapter, explain his disease in terms of amino acids. In the African American population, is the Sickle Cell allele a polymorphism.

sickle cell anemia is caused by the nonconservative change of  glutamate to a valine in the beta sheet region.  this swaps a polar amino acid for a nonpolar one.  carriers of the trait are more resistant to malaria so it survives in the population.

Concerning Cal Kullis: To the extent covered in this chapter, explain his disease in terms of amino acids.

this disease is caused by the decreased ability to excrete cystine from the kidneys.  treatment involves decreasing the intake of methionine, the cystine precursor.

Concerning Di Abetes and in terms of amino acids, explain the difference between pork insulin, lispro, and synthetic human insulin. What are the possible advantages of each.

Pork insulin is cheap but can lead to the development of an allergic response.  Synthetic human insulin has no allergic response. Lispro is fast acting so it can be used right before meals.

Concerning Ann Jeina, describe the isozymes of creatine kinase found in her body, their release following injury, and their use in diagnosing a myocardial infarction. Why do they react differently as antigens and why do they move differently in an electric field?

The MB form is particular to the heart. It leaks out during a heart attack and so elevated MB levels can be diagnostic.  They have different charges

Understand the meaning of primary, secondary, tertiary, and quaternary structure and be able to discern the difference.

[image]

Be able to recognize and discern between the three types of secondary structure discussed in class!

What is the location of the R-groups in an alpha helix? Can an alpha helix be formed from any primary sequence of amino acids?

What is the difference between parallel and antiparallel b-sheets? How do the R-groups protrude from the sheets?

Parallel beta sheets have their r groups on the same side. Anti-parallel sheets alternate which side the R groups project from.

What are the three names for nonregular, nonrepetitive secondary structures

bends, loops, and turns

Relatively small arrangements of secondary structure recognized in many different protiens.

Structural domains are elements of tertiary structure usually recognizable when looking at the overall protien.

What is a fold (fold structure or protein fold)? What is a fold family?

Folds are relatively large patterns of three dimensional strucure that have been identified in many protiens.  fold families are all descended from the same ancestral fold.

That they belong in the same fold family and descend from the same protein.

Where would you most likely find the nonpolar, polar and charged amino acids in a globular protein?

towards the center

along the edge

along the edge

 The LDH molecule always contains 4 polypeptide subunits and each subunit can be either a H (heart) or a M (muscle) subunit. How many isozymes are possible? Describe the isozymes in terms of the number of mers and homo or hetero.

hhmm, hhhm, hmmm, hhhh, mmmm

What are the forces that hold the monomer units of a quaternary structure together?

covalent, electrostatic, disulfide etc...

For a ligand-protein complex that dissociates into a ligand and protein. Be able to state the dissociation constant and the association constant.

Ka=[LP]/[L][P]

Kd=1/Ka = Disassociation constant

Using the terms ferrous iron, heme, hydrophobic pocket, histidine, alpha-helix, alpha-turns, salt bonds, hydrophobic interactions, hydrogen bonds, oxygen, and subunits, describe the myoglobin and hemoglobin molecule.

Be able to draw an oxygen dissociation curve for hemoglobin and myoglobin

A specific molecule a protein wants to bind.  (ATP, O2)

Tightly bound organic ligands such as the heme or hemeglobin.

Be able to explain why the oxygen saturation curve for hemoglobin is sigmoidal while the curve for myoglobin is a rectangular hyperbola. Include the terms subunits, O₂, Fe²⁺, conformation, salt bridges, T-state, R-state.

Because each additional O2 that is bound makes it easier for the hemeglobin to bind subsequent O2.  The salt bridges are what cause resistance and as they are broken it becomes easier to bind O2

Be able to describe the structure of IgG in terms of the number of chains, the number and types of domains, and the forces that hold the chains together. Which part binds to an antigen and why is it specific? What fold family do the domains belong to.

2 heavy and 2 light chains joined by a disulfide bond. the tips of the Y shaped structure bind to antigens.  immunoglobulin fold.

What is denaturation? Name a few ways that proteins are denatured in humans

Loss of secondary and above structure.

pH changes, glycosilation, temperature

Explain how a prion can cause dementia and death. Include the terms PrPc, PrPsc, template, activation energy, cascade, amyloid protein, and proteolytic degradation.

susceptible proteins are misfolded and cause others to misfold,  These protiens are nonfunctional and aggregate into a multimeric assembly that is resistant to proteolytic digestion.

Concerning Will Sichel: In biochemical terms, explain the development of pain during a sickle cell crises. Include the specific mutation, oxygen pressure, and protein conformation in your answer.

Pain is caused by loss of oxygen to affected tissues when sickle cells conglomerate and congest small blood vessels.

Concerning Anne Jeina: What are the three different proteins that appear in the blood following the beginning of a myocardial infarction? What are their normal cell functions? How soon can they be detected? How specific are they?

CK-MB, myoglobin, cTNT.

A protein

An oxygen binding protein

A subunit of a regulatory protein

2-6 hours

moderately specific

Concerning Amy Lloyd: What is an amyloid protein? What are the monomer units of the polymer in amyloidosis/AL? What secondary structure is found in amyloid fibers? What is an M-protein and why is it detected as a sharp peak upon serum protein electrophoresis?

Amyloid fibers a derived from immunoglobuin light chains.  Monoclonal protien component peaked because all the amyloid was derived from a single cell and its clones. 

Concerning Di Abietes, What is HbA_1c? How is it made and what does it measure?

glycosylated hemoglobin cause by nonenzymatic glycosylation.  It measures the levels of glucose in the blood over the past 4 to 6 weeks.

Explain the Induced Fit Theory Model for Substrate Binding. What was the major shortcoming of the Lock-and-Key Model for Substrate Binding?

Explain catalytic power in terms of the transition state and activation energy.

The enzyme lowers the activation energy needed for a reaction.

Be able to define the following terms: cofactor, coenzyme, and prosthetic group

Coenzymes are nonprotein organic cofactors. Prosthetic groups such as heme do not dissassociate until the enzyme is degraded. 

Form a covalent bond with the substrate. Holding it activates it for subsequent reactions.

With respect to thiamine pyrophosphate, what vitamin is it synthesized from? What group on substrate (pyruvate or a-ketoglutarate for example) is always attacked by this coenzyme? Which bond is broken?

Thiamine

The keto group

the adjacent c-c bond is cleaved

With respect to Coenzyme A, what vitamin is it synthesized from? What is its functional group on the coenzyme and what kind of bond does it form with the activated group? What types of groups are activated?

pantothenate

It contains a sulfhydryl group that binds to carbonyl substrates and forms an acyl thioester

Concerning biotin, what kind of enzyme uses this coenzyme and what do they do? What is the vitamin? Is biotin a prosthetic group?

carboxylases

Its nitrogen binds a CO2 group for transfer to the substrate.

Pantothenate

yes?

Concerning the cofactor pyridoxal phosphate, what type of group does it usually react with? What vitamins is it synthesized from?

the positively charged nitrogen ring draws electrons from and breaks a bond in the bound amino acid 

pyrodoxine

Concerning NAD⁺, what vitamin is it synthesized from? When lactate dehydrogenase or alcohol dehydrogenase oxidize their substrates, what is transferred to NAD⁺? Besides pyruvate and acetaldehyde, what is the other reaction product? What is the function of the ADP portion of NAD⁺?

niacin

electrons

a proton?

ADP causes a conformational change in the enzyme

Be able to draw a probable plot of activity versus pH for an enzyme that functions at pH=7.0.

Be able to draw a probable plot of activity versus temperature for a human enzyme.

What is the normal function of acetylcholinesterase? Explain how diisopropylphosphofluoridate causes the symptoms associated with it. Is this an irreversible inhibitor? Why?

How does aspirin inhibit prostaglandin endoperoxide synthase?

By transfering an acetyl group to the enzyme and irreversibly inhbiting it.

Concerning penicillin, why does it bind so readily to the active site of the enzyme? Is penicillin an irreversible inhibitor? Is penicillin a suicide inhibitor? Why?

It is a transition state analog

yes

yes, because it reacts with the enzyme irreversibly

What is the normal function of xanthine oxidase. Explain why allopurinol is used to treat gout. Is allopurinol an irreversible inhibitor? Is allopurinol a suicide inhibitor? Why?

oxidation of hypoxanthine to xanthine and xanthine to uric acid for excretion.

allopurinol irreversibly inhibits xanthine oxidase thereby preventing the generatin of uric acid

Be able to name the 6 major classes of enzymes. Given one of the following reactions, be able to match it with one of the 6 major classes of enzyme reactions catalyzed: alcohol dehydrogenase, glucokinase, chymotrypsin, aldolases, triosephosphate isomerase, and pyruvate carboxylase.

Be able to name the 6 major classes of enzymes. Given one of the following reactions, be able to match it with one of the 6 major classes of enzyme reactions catalyzed: alcohol dehydrogenase, glucokinase, chymotrypsin, aldolases, triosephosphate isomerase, and pyruvate carboxylase.

What is the difference between a synthase and a synthetase?

synthetase enzymes use ATP bound energy

synthases do not

Concerning Dennis "the menace" Veere, Explain how Malathion causes the symptoms associated with it. Is the inhibition irreversible? Why? Is this an example of a suicide inhibitor? Why?

it is converted in the liver to maloxon which binds to acetylcholinesterase in a reversible way but the bond ages and becomes irreversible.  Yes

Concerning Lotta Topaigne, Explain why allopurinol is used to treat gout. What is the normal reaction inhibited by this drug? Is allopurinol an irreversible inhibitor? Is allopurinol a suicide inhibitor? Why?

Allopurinol inhibits the excetory enzyme that create uric acid.  It is an irreversible suicide inhibitor

Concerning Al Martini, be able to write the equation for the first step in alcohol metabolism in humans. What vitamin is the coenzyme of this reaction synthesized from? What is the common vitamin deficiency seen in alcoholics? Why does it occur?

EtoH +NAD -> Acetaldehyde + NADH

zinc

Thiamine

No one knows

What are the terms found in the Michaelis-Menten equation and what do they mean? Draw a graph of vi versus [S] for a hypothetical Machaelis-Menten enzyme. What kind of curve is derived? Where are V_max and K_M on this curve?

Are glucokinase and hexokinase isozymes? Is hexokinase a Michaelis-Menten enzyme? Is glucokinase of liver or pancreas a Michaelis-Menten enzyme?

Yes

yes

yes, they have different Km and store glucose fastes at different concentrations

How does the S_0.5 for pancreatic glucokinase in some patients with MODY compare with normal patients? What effect does this have on insulin production and blood glucose levels?

They have a decreased activity of glucokinase resulting in less insulin production for a given level of blood glucose.

What is the effect of a competitive inhibitor on the K_M and V_max?

Increase apparent Km

do not affect Vmax

What is the effect of a noncompetitive inhibitor on the K_M and V_max?

Does not change Km

Lowers Vmax

How does product inhibition of hexokinase in one cell benefit all the other cells of the body?

By conserving blood glucose for other tissues that may need it.

What are the various names for the compounds that bind to an allosteric site? What affect do they have on the enzyme?

Activators and inhibitors

The substrates of allosteric enzymes exhibit positive cooperativity. Explain positive cooperativity in terms of subunits, conformation, and activity of the active site.

The binding of a substrate to one subunit facilitates the binding of subsequent substrates.

What is the difference between the T-conformation (state) and the R-conformation of an allosteric enzyme?

T: Taut state the inactive, unbound state

R: relaxed state  The active bound state.

its hard to bind to the T state but once you do other sites become R states and subsequent bindings are easier.

Understand the effect that allosteric activators and inhibitors have on the conformation of an allosteric enzyme and on the plot of velocity versus substrate concentration. What about the S_0.5?

 What is the general name for the enzyme that places phosphate groups onto an enzyme? What groups on the enzymes are typically phosphorylated? What are the effects of phosphorylation?

Protein kinase,

the hydroxyl group of serine or threonine

conformational changes of the catalytic site

can up or down regulate

What is the general name for the enzymes that hydrolyze and thus remove phosphate groups from proteins? What bond is usually broken? What are the effects of dephosphorylation?

Protein phosphatase

the CH2-O bond

A change in the active site conformation

can up or down regulate

Using the terms seryl residue, phosphorylation, positive allosteric effector allosteric site, phosphorylase b, phosphorylase a, conformation, and enzyme activity, explain how either AMP or phosphorylase kinase activates muscle glycogen phosphorylase. What is the effect of protein phosphatase upon phosphorylase a?

glycogen phosphorylase B is activated the addition of a phosphate group to a serine residue, or by binding with AMP.

Protein phosphatase removes the phosphate group and turns it off.

What are the activators of phosphorylase kinase in a muscle cell?

Protien Kinase A and calmodulin

Starting with an increase in the concentration of cAMP that resulted from adrenalin binding to a receptor in the cell membrane, explain how phosphorylase is activated. How does the cascade result in the amplification of the original signal?

cAMP activates and releases protein kinase A.

The amplification results when each subsequent reaction in the chain activates additional enzymes.

Explain how an increase in calcium in muscle cells simultaneously activates muscle contraction and glycogenolysis. Which system uses ATP and which helps to produce ATP?

Ca2+ binds muscle glycogen phosphorylase kinase leading to an increase in ATP

It also binds troponin-C preparing the muscle for contration.

How do G-proteins function? No need to mention GAPs, GEFs, GDIs, or the Ras family at this time.

By binding and hydrolyzing GTP

Are chymotrypsinogen and prothrombin zymogens? How are these enzymes activated?

chymotripsinogen is and I suspect prothrombin as well.

by cleavage of a peptide bond in the N-Terminus region.

hours to days

Name one hormone that induces ubiquitin in muscle tissue. What is the function of this process, i.e., what is the result of ubiquitin induction?

cortisol stimulates ubiquitin production thus preparing the body to degrade proteins for immune system boosting.

Why is it important that the regulatory (control) enzyme for a pathway, catalyze the rate limiting step in a pathway? How is the rate of this step (enzyme) controlled? What does the term committed step mean?

In order to slow the entire process.

Often through feedback inhibition by its end product

The first step that leads irreversibly to the end product.

Concerning Al Martini, what are the two principal mechanisms for catabolizing ethanol in humans? Be able to write the reaction for the most common mechanism that uses NAD⁺ as a cofactor.

the alchol dehydrogenase pathway that leads to acetalaldehyde and a proton.

The MEOS pathway

Concerning Al Martini, assume that the Vmax of cytosolic alcohol dehydrogenase enzyme and the MEOS system are equal in Al's liver and that the K_M's are 0.04 mM and 11 mM, respectively. Which will oxidize most of the alcohol consumed when the blood alcohol content is low. For example, after consuming 1 oz of alcohol and a blood alcohol of 6.4 mM. Why?

Alchol dehydrogenase will reach its Vmax at a much lower concentration and thus will do the majority of the work when the concentration is low.

Concerning Al Martini, explain how increasing the amount of alcohol oxidized by alcohol dehydrogenase will affect the rate at which alcohol is oxidized. How does this affect fatty acid oxidation?

While continued drinking stimulates additional MEOS production through gene transcription once Vmax is reached nothing further can be done. 

fatty acid???

Concerning Ann O'Rexia, in which of her tissues do you find hexokinase and glucokinase and what is the reaction these enzymes catalyze? When glucose-6-phosphate inhibits hexokinase, is this product inhibition?

hexokinase is in skeletal muscle while glucokinse is in the liver

the release of glucose into the blood from strored glycogen

Concerning Ann O'Rexia, what pathway is used when her cells wants to make energy from glucose-6-phosphate and how does the concentration of ATP in the cell affect the rate of this reaction? Is this feedback regulation? How does the concentration of AMP affect the rate of this reaction? Would you call this feedback or feed forward regulation? Is this positive allosteric regulation?

glycolysis. 

the ATP/AMP ration stimulates glycolysis and glyconeogenisis.

feed forward regulation

Yes its a postive allosteric

Concerning Ann O'Rexia, what pathway does she use for the storage of glucose as glycogen? How does glucose concentration and insulin affect this pathway? Is this feed forward regulation?

glycogen synthase

stimulated by high blood glucose levels and insulin,

yes

Concerning Ann O'Rexia who suffers from anorexia, if joging activates both glycogenolysis and glycolysis, why does Ann tire easily?

inadequte fuel stores are used up quickly, and her starved state has limited her ability to store glucose as glycogen since that pathway is feed foward regulated.

Concerning Ann O'Rexia, when she begins to jog, what muscle enzyme in glycogenolysis is activated by AMP? What type of activation is this? How does epinephrine activate this same enzyme? What role does cAMP and protein kinase A play in this cascade?

glycogen phosphorylase

allosteric feedback regulation

epinepherine activates cAMP which activates protein Kinase A which activates numerous enzymes including glycogen phosphorylase

Concerning Ann O'Rexia, when she begins to jog, what enzyme in glycolysis is activated? What type of activation is this?

phosphofructokinase 1

allosteric feedback regulation

Beginning with the release of a chemical messenger in response to a stimulus, list the common characteristics of all chemical messenger systems.

messenger is secreted in response to a stimulus

messenger diffuses or is transported to the target cell

binds to a receptor

receptor binding elicts a response

signal ceases and is terminated

What is a signal transduction pathway? Name two types of targets of signal transduction pathways.

Membrane spanning proteins that transfer a signal in one direction.

enzyme activation/inhibition

gene expression

Beginning with the response to a stimulus, list the common characteristics of all chemical messenger systems as they apply to the chemical messenger acetylcholine at the neuromuscular junction. Use the terms nerve cell action potential, Ca²⁺-channel, vesicles, fusion, presynaptic membrane, acetylcholine, diffusion, acetylcholine receptors, gated ion channels, muscle cell action potential, and acetylcholinesterase.

acetylcholine is the neurotransmitter released by a neuron

it diffuses across the synaptic cleft

binds to nicotinic acetylcholine receptors

opens the Na+ gateway

is terminated by acetylcholinesterase

Be able to determine when a chemical messenger is acting as an endocrine, paracrine, or autocrine substance.

endocrine: secreted into blood

paracrine: secreted into interstitial fluid

autocrine: self signaling

What is a major difference between chemical messengers that are specific for intracellular receptors and those that are specific for plasma membrane receptors?

intracellular messengers must be lipophilic to diffuse across the membrane

Describe the path taken by cortisol from the time it is released from the adrenal cortex until the time it affects gene transcription. Include serum albumin, steroid hormone binding globulin (SHBG), cortisol receptor, conformation change, nuclear translocation signal, dimerization, glucocorticoid response element (GRE), and regulation of gene transcription.

serum albumin or SHBG binds cortisol to transport it in the blood.  It binds the glucocorticoid receptor inside the cells causing a coformational change that exposes a nuclear translation signal. the receptors dimerize and move to the nucleus where bind the hormone response element GRE.

Concerning plasma membrane receptors for chemical messengers, how is the signal transduced? What are the two major effects upon the cell that result from chemical messenger binding?

an extracellular domain binds the messenger. one or more alpha helixes span the membrane and transmit a change to the intracellular domain which inititates the signal transduction. 

rapid changes in enzyme activity

slower changes in gene expression

protiens that bnind to the activated intracellular portion of a membrane receptor protein [Grb2, STAT, Smad]

When a protein contains a src homology 2 domain (SH₂ domain), what does it bind to? Is the binding specific?

phosphotyrosine residues on growth factor receptors. 

yes

In the Ras and MAP kinase pathway, how does the occupied receptor activate Grb2? What is the last step in the pathway that is catalyzed by MAP-kinase and what is the effect?

by binding to it with a phosphate. 

a gene transcription factor regulating cell proliferation and death

What are the functions served by phosphatidylinositol phosphates in signal transduction?

it can be cleaved into two different intracellular messengers

it can serve as a plasma membrane docking site for signal transduction proteins

What are the substrates and products of the reaction catalyzed by phospholipase C?

PI-4,5-bisP is cleaved into IP3 and DAG

What are the substrates and products of the reaction catalyzed by phosphatidylinositol 3’ kinase?

PI-4,5-bisP is phosphorylated to PI-3,4,5,-trisP

What is the function of a pleckstrin homology domain?

anchoring GrB2 to PI-3,4,5-trisP

What is the effect of insulin on protein synthesis and on glucose uptake and glycogen synthesis in muscle cells? Does this help to explain muscle wasting and hyperglycemia in a diabetic?

It increases protien synthesis, increases glucose uptake and glycogen synthesis. Yes low insulin decreases new muscle generation and does not take glucose out of the bloodstream as rapidly as it should.

 Be able to draw a cartoon of the insulin receptor that shows the cell membrane, two alpha-beta subunits, the membrane spanning region of the dimers, the insulin-binding site, the sites of tyrosine kinase domains, and the sites of auto-phosphorylation. Draw two IRS proteins bound to the receptor and indicate some of the sites phosphorylated on the IRS by the insulin receptor tyrosine kinases. Why do proteins bind to the phosphorylated IRS sites?

 In the insulin signal transduction pathway that begins with the activation of phosphatidylinositol 3' kinase, name the down stream active kinase that dissociates from the membrane. Is this kinase a tyrosine or a serine/threonine kinase?

protein kinase B. 

serine/threonine kinase

In the insulin signal transduction pathway that leads to the activation of MAP kinase, what is the signal transducer protein that binds to the IRS? Why does it bind to the IRS and why does it bind to the membrane?

Grb2

it binds a phosphate group on the IRS

it binds the membrane through PI-3,4,5-trisP

In the insulin signal transduction pathway that leads to increases in the diacylglycerol and inositoltrisphosphate second messengers, What is the first signal transducer protein that binds to the IRS? Why does it bind to the IRS.

phospholipase PLCy

It binds a phosporylated area of IRS

Explain the sequence of reactions that occur following the binding of glucagon or epinephrine to a heptahelical receptor. Include the terms: glucagon, epinephrine, heterotrimeric G proteins, a subunit, bg complex, GDP, GTP, tethered, lipid anchor, adenylyl cyclase, ATP, cAMP, PPi, and hydrolysis How long does the Gas protein stay active

receptor binds hormone

G protein exchanges GTP for GDP and disassociates

target protein binds GTP-Gas

GTP is hydrolyzed and Gas disassociates

Gas reassociates with betaY subunits and receptor

Gas: stimulates adenyl cyclase , regulates hormones, enzymes, some neurotransmitters

Gai: inhibits adenyl cyclase

Gaq: activates phospholipase

A mutated form of the G-protein Ras is found in many cancers. How are these mutations thought to affect the cell? Use the term internal clock in your answer.

Lack of an internal clock causes the signal to not shut off leading to uncontrolled proliferation

What is the response when epinephrine binds to an a1-adrenergic receptor? What is the response when epinephrine binds to a b-receptor? That is, what kind of G-protein is activated and what are the initial second messengers produced?

The betaY subunit inhibits adenyl cyclase

Name the enzyme that synthesizes cAMP, the enzyme that hydrolyses cAMP and the enzyme that is activated allosterically by cAMP. Which of these three enzyme reactions is affected by insulin?

adenyl cyclase

phosphodiesterase

protein kinase A

phosphodiesterase

When phosphatidyl inositol bisphosphate is hydrolyzed by phospholipase C, what is the next step in the signal transduction pathway for diacylglycerol? What are the next several steps in the signal transduction pathway for inositol trisphosphate? Use protein kinase C, target proteins, endoplasmic reticulum, calcium, calmodulin, and calmodulin binding proteins in your answer.

it creates second messengers DAG and IP3. 

IP3 stimulates the release of Ca2+ from the endoplasmic reticulum

Ca2+ activates calmodulin containing enzymes

DAG phosphorylates target proteins

Glucagon is released when blood sugar is low. How is its signal terminated (or lowered) following a high carbohydrate meal that increases the blood sugar?

Concerning Mya Sthenia who has myasthenia gravis, explain how her chemical messenger system differs from a normal person. How did this happen? Why do the anticholinesterase drugs do to temporarily alleviate the problem?

Her Nicotinc acetalcholinesterase receptors have been attacked by the immune system.  they increase the consentration of acetylcholinesterase avaliable to stimulate the remaining receptors.

Concerning Ann O'Rexia who has been fasting and is jogging, what was the stimulus for the release of glucagon, epinephrine, norepinephrine, and cortisol? From what cells and what tissue did glucagon originate? From what tissues did epinephrine, norepinephrine, and cortisol originate? What is the effect of all these hormones upon the release of glucose from liver and free fatty acids from adipose tissue?

low blood sugar, excercise, excercise, excercise

alpha cells of the pancreas

adrenal medulla [epi, norepi]

adrenal cortex [cortisol]

release glucose form the liver and adipose tissues

Concerning Ann O'Rexia who has been fasting, why is her blood glucagon increased? Why does glucagon have an effect upon adipose and liver tissue but not upon skeletal muscle tissue?

low blodd glucose stimulates release of glucagon

skeletal muscle lacks receptors

Concerning Ann O'Rexia, what are the two general mechanisms (ways) that glucagon, epinephrine and other hormones use to elicit a response in target cells?

enzyme activity

gene transcription

Concerning Dennis Veere who has cholera, how does the cholera A toxin change the metabolism of the intestinal cell? Use ADP-ribosylation factor, NAD, ADP ribose, ADP-ribosylates, Gas subunit, adenyl cyclase, cAMP, CFTR channel, chloride ion, sodium, and diarrhea in your answer.

the toxin causes NAD cleavage and ADP ribosylation of Gas thereby inhibiting their GTPase activity.  This increases cAMp production the CFTR channel is activatedand Cl+ and Na+ are dumped into the intestinal lumen. this causes dehydration, vomiting, and diarhea