Ch 10, 11, 13, 14, 16

Question 1

Calculate the standard free-energy change of the reaction catalyzed by the enzyme phosphoglucomutase given that starting with 20 mM glucose 1-phosphate and no glucose 6-phosphate, the final equilibrium mixture at 25ºC and pH 7.0 contains 1.0 mM glucose 1-phosphate and 19 mM glucose 6-phosphate.

Does the reaction in the direction of glucose 6-phosphate formation proceed with a loss or a gain of free energy?

Answer 1

First, calculate the equilibrium constant.

Then, calculate the standard free-energy change

Question 2

What is the difference between ∆Gº’ and ∆G?

How are they related?

Answer 2

The standard transformed free energy change (∆Gº’) tells us in which direction and how far a given reaction must go to reach equilibrium when the concentration of each component is 1.0 M, the pH is 7.0, the temperature is 25ºC, and the pressure is 101.3 kPa (1 atm). Thus ∆Gº’ is a constant.

The actual free energy change/Gibbs free energy (∆G) is a function of reactant and product concentrations and of the temperature prevailing during the reaction. The ∆G of any reaction proceeding spontaneously toward its equilibrium is always negative, becomes less negative as the reaction proceeds, and is zero at the point of equilibrium.

Question 3

actual free-energy change (∆G) = 0 vs standard free-energy change (∆Gº’) = 0

Answer 3

∆G=0: implies that the reaction is at equilibrium (no more work is done by the reaction in either direction)

∆Gº’ = 0: implies that the equilibrium constant (the concentrations of reactants and products at equilibrium) is 1

Question 4

What are the conditions in which metabolic reactions with a large positive ∆Gº’ can still be exergonic?

Answer 4

A reaction with a positive standard-free energy change can go in the forward direction if ∆G is negative.

Immediate removal of products to keep the ratio of products to reactants well below 1 so that the term RTlnQ has a large, negative value

Question 5

FRAP

Fluorescence Recovery After Photobleaching

Answer 5

allows us to monitor lateral lipid diffusion by monitoring the rate of fluorescence return; the diffusion coefficient of lipid in the leaflet can be determined

rates of lateral diffusion are high (up to 1µm/sec); a lipid can circumnavigate E. coli cell in one second

Question 6

Membrane Rafts

Answer 6

there’s also different lipid distribution within a membrane (not only between membranes)

lipid rafts

• contain clusters of glycosphingolipids with longer-than-usual tails (more opportunity for van der Waals interaction, giving more stability)
• are more ordered
• contain specific doubly or triply acylated proteins
• allow segregation of proteins in the membrane

Question 7

Caveolin

Answer 7

when several caveolin dimers are concentrated in a small region (a raft) they force a curvature in the lipid bilayer, forming a caveola

flattening of caveolae allows the plasma membrane to expand (increase surface area)

Question 8

other modes (besides caveolin) of membrane curvature

Answer 8

1. a protein with intrinsic curvature and a high density of positive charge on its concave surface
2. a protein with one or several amphipathic helices inserted into the outer leaflet of the bilayer
3. proteins with BAR domains can polymerize into a superstructure that favors and maintains the curvature

Question 9

membrane fusion

Answer 9

membranes can fuse with each other without losing continuity

fusion can be spontaneous or protein-mediated

examples of protein-mediated fusion: entry of influenza virus into the host cell and release of neurotransmitters at nerve synapses

Question 10

Why is passive diffusion of polar molecules across membranes unfavorable?

Answer 10

involves desolvation and thus has a high activation barrier

Question 11

What are the 3 classes of transport systems?

Answer 11

1. uniport: facilitated diffusion
2. symport (cotransport): secondary active transport
3. antiport (cotransport): secondary active transport

Question 12

Glucose transport

Answer 12

1. glucose in blood plasma binds to T1
2. conformational change from T1 to T2
3. glucose is released from T2 into the cytoplasm
4. the transporter returns to T1

Question 13

There are multiple glucose transporters

Answer 13

A Na+-glucose symporter (intestinal lumen) and a glucose uniporter (blood) operate on opposite sides of epithelial cells

cells can also have asymmetry with distinct proteins confined to one side

Question 14

Bicarbonate transporter

Answer 14

antiporter: chloride-bicarbonate exchanger

maintains the electrochemical potential across the membrane

Question 15

two types of active transport

Answer 15

a) primary active transport: energy released by ATP hydrolysis drives solute movement against an electrochemical gradient
b) secondary active transport: a gradient of an ion has been established by primary active transport; movement of S1 down its gradient now provides energy to drive cotransport of a second solute against its electrochemical gradient

Question 16

ABC Transporters

Answer 16

a large family of ATP-driven transporters that pump ions and molecules against a concentration gradient

located in the plasma membrane, in the ER, mitochondria, and lysosomes

CFTR protein of the plasma membrane (airway epithelium):

• ion channel for Cl
• when it doesn’t work, cystic fibrosis; mucus accumulates, entrapping bacteria that results in infection of lungs and airway

Question 17

Proton pumps

Answer 17

ATPase uses ATP to pump protons through the membrane

the energy of the proton gradient can be used to make ATP (in chloroplast and mitochondrial membranes) by ATP synthase

Question 18

aquaporins

Answer 18

allow rapid water passage through membranes

size restriction: the pore narrows at His 180 to a certain diameter, limiting the passage of molecules larger than H2O.

electrostatic repulsion: the positive charge of Arg 195 repels cations, including H3O+

water dipole reorientation: the helices with Asn-Pro-Ala are oriented with their positively charged dipoles pointed at the pore to force H2O to reorient as it passes through; this breaks up hydrogen-bonded chains of water molecules and prevents proton passage by proton hopping

Question 19

K+ channels and their specificity

Answer 19

at the inner and outer plasma membrane surfaces, the entryways to the channel have several negatively charged amino acid residues

the pore is a specific diameter that allows a specific ion and its water shell to pass through the channel

Question 20

How do major nucleotide mutations occur?

Answer 20

naturally

radiation

reactive chemicals

Question 21

Accumulation of nucleotide mutations is linked to what?

Answer 21

aging and carcinogenesis

Question 22

What are the two types of naturally occurring mutation reactions?

Answer 22

deamination and depurination

Question 23

deamination

Answer 23

very slow reaction; occurs one in 10⁷ cytosine residues per day (~100 spontaneous events per day); adenine to guanine occurs much slower (1/100th the rate of C to U)

cytosine is mutated to uracil; uracil is recognized as foreign in DNA and removed by a repair system

thymine allows for long-term storage of genetic information; otherwise, AU not recognized as mutation, and eventually GC will be eliminated

Question 24

depurination

Answer 24

N-glycosidic bond is hydrolyzed; the base is lost, creating an abasic site

purines are lost at a higher rate than pyrimidines (10,000 purines lost per day in one mammalian cell); depurination of RNA is much slower and less physiologically significant

proteins recognize damage and fill in gap

Question 25

What are the two types of mutations caused by radiation?

Answer 25

1. thymine dimers (UV) * cause kink in DNA, blocking the movement of polymerases * fixed by nucleotide excision repair (E. coli handles the repair differently than humans) 2. fragmentation of nucleic acids (ionizing radiation like x rays and gamma rays) * difficult to fix * high energy traverses the cell and collides with water, resulting in oxygen radicals that react with molecules in the cell

Question 26

What are the two different ways reactive chemicals can cause nucleotide mutations?

Answer 26

1. oxidative damage * reactive oxygen species arise during irradiation or as a byproduct of aerobic metabolism (mitochondrial DNA is most susceptible) * damage DNA: oxidation of deoxyribose, hydroxylation of guanine, and break strands; accumulate as you age * cell destroy reactive oxygen species, but a fraction escape 2. alkylating agents * dimethylsulfate can methylate guanine, preventing base pair with C * S-adenosyl methionine normally present in cells (not a mutagen) * cancer treatment: lots of side effects because we're killing good cells too

Question 27

What are some other functions of nucleotides besides the storage of genetic information?

Answer 27

1. energy source: ATP, UTP, GTP, CTP * hydrolysis of ester linkage and anhydride bond in nucleoside triphosphates provides chemical energy to drive many reactions 2. components of enzyme cofactors: adenine dinucleotides (Coenzyme A, NAD+, FAD) * adenosine do not directly participate in the primary function, but the removal of adenosine results in a drastic reduction of cofactor activities 3. regulatory molecules: second messengers bind to receptors on the cell surface, leading to changes in the cell interior * cAMP: slime molds, unicellular form, and fruiting body * ppGpp: produced in bacteria in response to amino acid starvation; inhibits synthesis of tRNA and rRNA * cGMP

Question 28

DNA Sequencing

Answer 28

* makes a DNA strand complementary to the strand under analysis * a primer is annealed to the template DNA and polymerase extends it * ddNTPs are added in small amounts (10%) along with lots of dNTPs * ddNTPs interrupt DNA synthesis because they lack the 3' –OH needed to add the next nucleotide * a small fraction of the synthesized strands are prematurely terminated, resulting in a solution with a mixture of fragments * the different-sized fragments are separated by electrophoresis; the shortest strands (sequences closest to the primer) move farthest * now reading is automated: each of the ddNTPs is fluorescently tagged with a different color; expose to UV light and the computer helps with sequencing

Question 29

What are the different types of lipids and their classes?

Answer 29

* lipids that do not contain fatty acids: cholesterol, terpenes * lipids that contain fatty acids (complex lipids) * storage lipids (hydrophobic) * triacylglycerols * wax * membrane lipids (hydrophilic; charged head groups) * glycerophospholipids * sphingolipids

Question 30

Fatty Acids

Answer 30

carboxylic acids with hydrocarbon chains containing 4 to 36 carbon atoms almost all naturally occurring fatty acids (in our diets) have an even number of carbons in an unbranched chain of 12 to 24 hydrocarbon chains are saturated, monounsaturated (oleic acid), or polyunsaturated (omega-3 fatty acids: ALA, DHA, EPA) humans can't make ALA but can make EPH and DHA from ALA

Question 31

trans fatty acids

Answer 31

unnatural trans configuration of double bonds formed by partial hydrogenation of unsaturated fatty acids to increase shelf-life (margarine) or stability at high temperature (deep-frying oils) found in dairy products and meats associated with high heart disease: increase LDL and lower HDL melting point is in-between unsaturated and saturated fatty acids because of its extended conformation

Question 32

omega-3 fatty acid nomenclature

Answer 32

the carbon of the methyl group (most distant from the carboxyl group) is called the omega carbon and is given the number 1 the positions of the double bonds are indicated relative to the omega carbon

Question 33

How is the solubility and melting point of fatty acids affected when their chain length increases? When their double bonds increase?

Answer 33

the longer the fatty acyl chain and the fewer the double bonds, the lower the solubility in water and higher the melting point the carboxylic acid group is polar and charged at neutral pH, which accounts for the slight solubility of short-chain fatty acids; when the chain grows longer, the charge to size ratio decreases hydrophobicity drives saturated fatty acids together; the fully extended form are packed tightly and the atoms all along the length of the chain are in van der Waals contact with the atoms of another fatty acid chain; this requires lots of thermal energy (higher T_m) to disorder packing

Question 34

triacylglycerols

Answer 34

aka triglycerides or fats most common and simplest lipid formed from 3 fatty acids in ester linkage with a glycerol * simple triglycerides: same fatty acids * mixed triglycerides: most naturally occurring; mixed fatty acid chains insoluble and less dense than water (fats and oils float) function: store energy; provide insulation

Question 35

advantage of fats over glycogen/starch to store energy

Answer 35

fatty acids carry more energy per carbon because they are more reduced fatty acids carry less water per gram because they are nonpolar adipocytes (fat cells) in vertebrates store large amounts of triglycerides that could be used as energy for months (good storage, slow delivery) the human body stores less than a day's energy supply in the form of glycogen (short-term energy needs, quick delivery because of solubility in water)

Question 36

wax

Answer 36

esters of long-chain saturated and unsaturated fatty acids with long-chain alcohols insoluble and higher melting points than triglycerides function: * store fuel in plankton * protect hair and skin in vertebrates and keep it pliable * waterproofing of feathers in birds * protection from evaporation in tropical plants and ivy * used by people in lotions, ointments, and polishes

Question 37

glycerophospholipid

Answer 37

aka phosphoglycerides primary constituents of cell membranes 2 fatty acids form ester linkages with glycerol and one highly polar/charged group is attached via a phosphodiester linkage to the third carbon different organisms and tissues have different membrane lipid head group compositions; the head groups determine the surface proteins of membranes lots of diversity possible by modifying backbone or the head groups, and changing fatty acids * phosphatidic acid * phosphatidylserine * phosphatidylcholine: a major component of most eukaryotic cell membranes; many prokaryotes like E. Coli cannot synthesize this lipid

Question 38

Ether Lipids

Answer 38

ether analogs of glycerophospholipids plasmalogen: ether analog of phosphatidylethanolamine * common in vertebrate heart tissue (heart is about 50% ether lipids) * also found in some protozoa and anaerobic bacteria * function not well understood: resistant to cleavage by common lipases (only cleaved by few specific); increase membrane rigidity; sources of signaling lipids; may be antioxidants platelets-activating factor: ether analog of phosphatidylcholine * acetic acid has esterified position C2 * signaling lipid * plays an important role in inflammation and allergic response * stimulates aggregation of blood platelets

Question 39

sphingolipids

Answer 39

the backbone is not glycerol; it's sphingosine ceramide is the structural parent of all sphingolipids 3 subclasses (ceramide derivatives): sphingomyelins (phosphocholine), glycosphingolipids (sugars), and gangliosides (oligosaccharides + sialic acid)

Question 40

sphingomyelins

Answer 40

phosphocholine head group structurally similar to phosphatidylcholine (glycerophospholipid) but phosphatidylcholine has 2 FAs and sphingomyelin has one found in plasma membrane and myelin sheath

Question 41

glycosphingolipids

Answer 41

one sugar linked to ceramide (outer face of plasma membrane) * galactose: in the plasma membrane of cells in neural tissue * glucose: in plasma membranes of nonneural tissue oligosaccharide linked: determinants of blood groups * no glycosyltransferase: O antigen (universal donor) * glycosyltransferase that transfers N-acetylgalactosamine: A blood gorup * glycosyltransferase that transfers galactose: B blood group * both versions of glycosyltransferase: AB blood group

Question 42

structural lipid metabolism and diseases

Answer 42

polar lipids of membranes undergo constant metabolic turnover the breakdown is promoted by hydrolytic enzymes in lysosomes mutations in genes of these enzymes results in partial breakdown products accumulating in the tissue (change membrane fluidity), causing serious diseases

Question 43

sterols

Answer 43

lipids without fatty acid; consists of steroid nucleus (4 fused rings) that's almost planar and rigid bacteria cannot synthesize sterols in eukaryotes, sterols increase membrane rigidity and decrease permeability * animals: cholesterol * plants: phytosterols * fungi: ergosterol

Question 44

biologically active lipids

Answer 44

present in smaller amounts than storage or structural lipids ## Footnote eicosanoids, steroid hormones, bile salts, fat-soluble vitamins (ADEK), and polyketides

Question 45

eicosanoids

Answer 45

carry messages to nearby cells (signaling lipid) arachidonic acid derivative; arachidonic acid is a metabolite of the omega-6 fatty acid (linoleate) NSAIDs block the formation of eicosanoids like prostaglandins (inflammation and fever) and thromboxanes (formation of blood clots)

Question 46

steroid hormones

Answer 46

carry messages between tissues (regulate gene expression) made from cholesterol in gonads and adrenal glands; have steroid nucleus but lack the alkyl chain (more polar) carried through bloodstream usually attached to carrier proteins

Question 47

Bile salts

Answer 47

emulsify dietary fats in the intestine to make them more readily accessible to digestive lipases polar derivatives of cholesterol

Question 48

vitamin D

Answer 48

formed in the skin from cholesterol in a reaction driven by UV light converted by enzymes in the liver and kidney to calcitriol (a hormone that regulates calcium uptake in the intestine and calcium levels in kidney and bone)

Question 49

vitamin A (B-carotene)

Answer 49

precursor for other hormones involved in signaling (regulate gene expression central to embryonic development); involved in visual pigment from our diet (carrot), converted to retinol that binds to the receptor proteins

Question 50

vitamins E and K and lipid quinones

Answer 50

from our diet antioxidants: react with and destroy the most reactive forms of oxygen radicals and other free radicals, preventing oxidative damage

Question 51

polyketides

Answer 51

have medicine uses erythromycin: antibiotic amphotericin: antifungal (toxic to humans) lovastatin: inhibitors of cholesterol synthesis

Question 52

self-aggregating lipid structures

Answer 52

spontaneously formed and stabilized via hydrophobic effect micelles * cross-section of the head is greater than that of the fatty acid side chain (wedge-shaped) * critical micelle concentration: minimum concentration of molecules required for aggregation (micelle formation) vesicles (liposomes) * the cross-section is in between wedge-shaped and cylindrical shaped * useful artificial carriers of molecules; central aqueous cavity can enclose drugs, DNA, and other polar/charged molecules bilaminar membranes (membrane bilayer) * cross-section of head equals side chain (cylindrical) * electrically polarized (inside negative ~–60 mV)

Question 53

membrane fluidity

Answer 53

uder physiological conditions, membranes are more fluid-like than gel-like for proper function (2D diffusion of proteins and phospholipids) * at higher temperatures, cells need more saturated fatty acids to maintain the integrity * at lower temperatures, cells need more unsaturated fatty acids to maintain fluidity

Question 54

cholesterol

Answer 54

major sterol in animal tissues amphipathic: polar head group at C-3 of A-ring and nonpolar body (steroid nucleus and hydrocarbon side chain at C-17) mammals obtain cholesterol from food or synthesize it in the liver cholesterol bound to proteins is transported to tissues via blood vessels cholesterol in LDL proteins tend to deposit and clog arteries

Question 55

asymmetric bilayers

Answer 55

the outer leaflet is more positively charged: phosphatidylcholine and sphingomyelin; carbohydrates (glycosphingolipids for ABO blood typing) phosphatidylserine is on the inside; when outside, activates blood clotting (platelets) and marks cell for destruction (other cells) *

Question 56

farnesylation

Answer 56

* targets proteins to the inner leaflet; * farnesyl transferase link proteins to the inner leaflet * protein sequence has the signature for farnesylation (Caax) * C is conserved Cys * "A" is usually an aliphatic amino acid * "X" is met, ser, Glu or Ala * non farnesylated proteins do not go to the membrane and are inactive (onco-Ras cancer therapy)

Question 57

membrane proteins

Answer 57

peripheral proteins: weakly associated with one side of the membrane * interact with charged heads of membranes and integral proteins * lipid-linked: more on the inside of the cell * removed easily by disrupting ionic interactions (high salt concentration or change in pH); purified proteins are no longer associated with lipids integral proteins: a-helices or beta-sheets span the entire membrane * asymmetric: different domains on different sides of the membranes * Tyr and Trp are clustered at the lipid-water interface * harder to purify; removed by detergents that disrupt the membrane; purified proteins still have phospholipids associated with them amphitropic proteins: found in the cytosol; associate reversibly with membranes

Question 58

lipid diffusion

Answer 58

lateral diffusion: very fast at room temperature; uncatalyzed transverse diffusion: very slow when uncatalyzed; spontaneous flips are rare because the charged head group must cross the hydrophobic tail region * flippase: catalyze transverse diffusion of PE and PS from outer to cytosolic leaflet against the concentration gradient (use ATP) * floppase: moves phospholipids from cytosolic to outer leaflet using ATP * scramblase: moves lipids in either direction toward equilibrium; thermodynamically neutral process

Question 59

What is the difference between standard free energy change and standard transformed free energy change?

Answer 59

standard free-energy change (∆Gº): is the force driving the system toward equilibrium under standard conditions: 298K = 25ºC), reactants and products are 1 M concentrations, or gases at partial pressures of 101.3 kPa or 1 atm. Because [H+] would be 1 M, pH would be 0 standard transformed free-energy change (∆G'º): force driving the system toward equilibrium under biochemical standard state: [H+] = 10^-7 (pH 7) and for reactions involving Mg²⁺ (most reactions with ATP as reactant), [Mg²⁺] = 1 mM

Question 60

oxidation-reduction reactions

Answer 60

many biochemical reactions involve the transfer (and acceptance) of two electrons and two protons in the form of a proton and a hydride ion; these reactions are commonly called dehydrogenations oxidation reactions generally release energy; in many dehydrogenases, the reaction proceeds by a stepwise transfer electrons to carriers like NAD, which is reduced to NADH

Question 61

pyridine nucleotides

Answer 61

NAD and NADP (common redox cofactors) * only carriers that are soluble * can dissociate from the enzyme after the reaction * in a typical biological oxidation reaction, the hydride from alcohol is transferred to NAD+/NADP+, giving NADH/NADPH * the second proton is released to the aqueous solvent * formation of NADH can be monitored by UV spectrophotometry (measure change of absorbance at 340 nm)

Question 62

flavin nucleotides

Answer 62

FMN and FAD: common redox cofactors (not soluble) tightly bound to flavoprotein, which holds onto electrons while it catalyzes the electron transfer from a reduced substrate to an electron acceptor fused ring structure undergoes reversible reduction, accepting either one or two electrons in the form of one or two hydrogen atoms (each atom an electron plus a proton); fully reduced forms (accept 2 electrons) are FADH2 and FMNH2 permits the use of molecular oxygen as an ultimate electron acceptor (flavin-dependent oxidases)

Question 63

List glycolytic entry points for other carbohydrates

Answer 63

dietary glycogen/starch: * amylase hydrolyze glycosidic linkages, producing short polysaccharide fragments * eventually, make d-glucose disaccharides * sucrose: broken down to glucose and fructose by sucrase * lactose: broken down to glucose and galactose by lactase * hexoses and fructoses are phosphorylated by the appropriate kinase

Question 64

Glycolysis: The Preparatory Phase

Answer 64

2 ATPs are invested to raise the free-energy content of the intermediates; all the metabolized hexoses are converted to 2 glyceraldehyde 3-phosphates step 3 (with phosphofructokinase-1) is the committing step to glycolysis; fructose 1,6-bisphosphate is not used in other biochemical reactions and is committed to becoming pyruvate and yield energy

Question 65

Glycolysis: The Payoff Phase

Answer 65

step 6: first energy-yielding step (NADH); use of inorganic phosphate allows for net production of ATP step 7: substrate-level phosphorylation (oxidation of bisphosphoglycerate) by phosphoglycerate kinase yields 2 ATP step 10: 2nd production of ATP via substrate-level phosphorylation; pyruvate tautomerization drives ATP production by lowering reaction product

Question 66

glycolysis in tumor cells

Answer 66

glycolysis occurs at elevated rates because cancer cells are hypoxic aerobic conditions yield 30-32 ATPs; anaerobic = 2 ATPs

Question 67

how is glucose transported into cells?

Answer 67

insulin binds to cells, triggering placement of glucose transporter into the membrane glucose transporter brings in glucose via facilitated diffusion

Question 68

phosphorylation of glucose

Answer 68

hexokinase in eukaryotes and glucokinase in prokaryotes highly thermodynamically favorable (irreversible) conversion of glucose to glucose 6-phosphate keeps glucose trapped in the cell (prevent it from going back into the lumen) phosphorylation also maintains glucose gradient to allow for continued facilitated diffusion of glucose

Question 69

substrate-level phosphorylation vs oxidative phosphorylation

Answer 69

substrate-level: formation of ATP by phosphoryl group transfer from a substrate; involve soluble enzymes and chemical intermediates oxidative phosphorylation: involve membrane-bound enzymes and transmembrane gradients of protons to form ATP

Question 70

fates of pyruvate

Answer 70

catabolic * aerobic metabolism: oxidized to yield acetyl CoA, which is completely oxidized to CO₂ by the citric acid cycle * lactic acid fermentation: reduced to lactate; accept electrons from NADH to regenerate NAD+; necessary for glycolysis to continue (generate ATP) * ethanol fermentation: two-step irreversible reduction to ethanol; pyruvate decarboxylase (humans don't have) and alcohol dehydrogenase anabolic: synthesis of alanine and fatty acids

Question 71

Cori Cycle

Answer 71

during strenuous exercise, lactate builds up in the muscle; the acidification of muscle prevents its continuous strenuous work lactate is transported to the liver and converted to glucose (gluconeogenesis); ATP is used

Question 72

Why do we need gluconeogenesis?

Answer 72

brain, nervous system, and red blood cells generate ATP only from glucose gluconeogenesis generates glucose for use by these organs/cells during fasts or starvation (when glycogen stores are depleted) helps manage blood glucose levels

Question 73

Pentose Phosphate Pathway

Answer 73

glucose 6-phosphate is shuttled to this pathway instead of being converted to pyruvate in glycolysis main products: * NADPH * electron donors during biosynthesis of fatty acids and steroids * repair oxidative damage * ribose 5-phosphate * a biosynthetic precursor of nucleotides (DNA, RNA, and coenzymes)

Question 74

energy scorecards for glycolysis and for gluconeogenesis?

Answer 74

gluconeogenesis very expensive; uses 4 extra high-energy nucleotides to drive the synthesis of glucose

Question 75

glycolysis location, feedstock, products, and regulated enzymes?

Answer 75

location: cytoplasm of muscle and brain main feedstock/substrate: glucose and 2 ATPs final products (per glucose): 2 pyruvates; 4 ATPs; 2 NADH regulated enzymes: hexokinase, phosphofructokinase, pyruvate kinase

Question 76

gluconeogenesis location, main feedstock, final products, and regulated enzymes

Answer 76

location: mitochondria, cytoplasm, ER (liver), sometimes in kidneys main feedstock: pyruvate (or oxaloacetate, lactate, and glycerol) final products: glucose 6-phosphate and glucose (in liver) regulated enzymes: pyruvate carboxylase, phosphoenolpyruvate (PEP) carboxykinase, fructose 1,6-bisphosphatase-1

Question 77

What are the steps in gluconeogenesis that bypass the irreversible steps in glycolysis?

Answer 77

pyruvate carboxylase and PEP carboxykinase * bypass pyruvate kinase: phosphoenolpyruvate to pyruvate * convert pyruvate to oxaloacetate (in mitochondria) and then phosphoenolpyruvate (in mitochondria or cytosol) * requires ATP and GTP fructose 1,6-bisphosphatase-1 * bypass phosphofructokinase-1 glucose 6-phosphatase * bypass hexokinase

Question 78

››Pyruvate dehydrogenase complex reaction, location, final products, cofactors, regulation

Answer 78

oxidative decarboxylation of pyruvate catalyzed by a huge (144 peptides) complex location: mitochondrial matrix; requires transport of pyruvate from the cytosol into mitochondria final products: acetyl-CoA, NADH, CO₂ cofactors: TPP, lipoic acid, FAD, NAD+ regulation: allosteric and covalent modification

Question 79

Why is the reaction of the PDH complex irreversible?

Answer 79

the short distance between catalytic sites allows channeling of substrates from one catalytic site to another, which minimizes side reactions locks in carbons from pyruvate regulation of activity of one subunit affects the entire complex