BIOC 221 - Midterm #2 (advanced editor) Flashcards

Question

Pyruvate Oxidation to Acetyl-CoA and then CAC **Location**?

Answer 1

occur in **mitochondria**

Answer 2

pyruvate needs to be transported from cytosol to mitochondrial matrix across two mito. membranes

Answer 3

Inner: highly selective, has specific carrier systems for specific metabolites Outer: non-specific pores that allows free passage of small metabolites

Answer 4

shuttled into mitochondria by a specific carrier system in exchange for hydroxide ion

Answer 5

initiator of CAC link between glycolysis and CAC

Answer 6

catalyzed by **Pyruvate Dehydrogenase Complex (E1 + E2 + E3) ** CoA-SH, NAD+, TPP, Lipoate, FAD CO2 and NADH produced IRREVERSIBLE

Answer 7

even numbered FAs impossible **Odd numbers FA's** produce **propionyl-CoA** (3C) which is converted to **pyruvate** via **succinyl-CoA** and **OAA**

Answer 8

multi enzyme complex series of intermediates remain bound to enzyme molecules easy flow of intermediated from one active site to another during sequential reactions **(substrate channeling) ** complex, well coordinated regulation

Answer 9

lipoamide Vit B1- **thiamine** (TPP) B2 - **riboflavin** (FAD) B3 - **niacin** (NAD) B5 - **pantothenic** **acid** (part of CoA-SH)

Answer 10

pyruvate decarboxylated remaining hydroxyethyl (2C) group is attached to TPP in E1

Answer 11

derivate of thiamine (vitamin B1) nutritional deficiency --\> **Beriberi** (loss of neural function) - especially affects brain which usually obtains all E from aerobic oxidation of glucose (that includes ox. of pyruvate)

Answer 12

electron sink H+ dissociates from C between N and S to yield carbanion e-deficient keto C of pyruvate is attacked by carbanion then decarboxylation facilitated by e delocalization 2C hydroxyethyl group is now attached to TPP in E1

Answer 13

Hydroxyethyl (2C) group transferred to lipoamide and is concomitantly oxidized to acetyl group in E1

Answer 14

long, flexible arm links lipoamide to E2 (core of the complex) allowing dithiol of lipoamide to swing from one active site to another

Answer 15

acetyl group is transfered from lipoamide to CoA (in E2) at the same time, lipoamide is reduced

Answer 16

dihydrolipoamide is reoxidized to disulfide (-S-S-) form and E3-disulfide is reduced

Answer 17

the -SH group of E3 are reoxidized by mechanism in which FAD funnels 2e to NAD+ yielding NADH FAD appears to function as an e conduit (channel)

Answer 18

Pyruvate decarboxylated & oxidized by NAD+ to acetyl in acetyl-CoA (by now 2C of glucose are lost as CO2) Free E released during pyruvate ox. is partially stored in NADH & thioster bond in acetyl-CoA

Answer 19

can easily donate acetate based on its high E thioester linkage

Answer 20

Continuation of **glucose oxidation** to CO2

Answer 21

**2 ATP** and **2** **NADH** from glycolysis **2 NADH** from PDH reaction

Answer 22

**degredation** of all nutrients (carbs, many aa's and fat) comes to acetyl-CoA

Answer 23

releasing remaining 2 carbons (originally from glucose) in acetyl-coA as CO2 and retaining the free E in the form of ATP, NADH, FADH2

Answer 24

the 2 C in ac-CoA arent directly converted to CO2 (chemically unfeasable). As the wheel turns, we lose 2CO2 through ox. & decarboxylation per 1 ac-CoA that enters the wheel

Answer 25

Acetyl-CoA + OAA --\> citrate In: **H2O** Out: **CoA-SH** catalyzed by: **citrate synthase**

Answer 26

Citrate synthase: **aldol & hydrolysis** binding of OAA to citrate synthase causes a conformation change that opens ac-CoA binding site **(induced fit)** transient intermediate: **citroyl-coA** citrate is a tricarboxylic acid -∆G endergonic b/c its irreversible rxn - regulation point

Answer 27

**inhibited by:** - high **^ATP/_ADP**and **^NADH/_NAD+** ratios (high ATP and NADH indicate high E supply for cell) - **succinyl-CoA** (feedback inhibition) - **citrate** (product inhibition)

Answer 28

reversible hydration **Citrate** --\> [cis-aconitate] --\> **Isocitrate** H2O out then H2O in catalyzed by: **Aconitase (aconitate hydratase)** 2˚ alcohol to 3˚ alcohol (isomerization) ENDERGONIC (+ΔG)

Answer 29

reversible hydration 3˚ alcohol to 2˚ alcohol +∆G: Isocitrate is quickly consumed in cell (mass action) contains Fe-S cluster that aids rxn & binds substrate intermediate enol compound - cis-Aconitate

Answer 30

Citrate has 3 –COO– groups, which are almost fully **oxidized** and ready to be removed as CO2. easiest way to lose CO2 is through ß-keto decarbox citrate has no keto , just 1 OH OH needs to be oxidized to keto OH group of 3˚ alcohol cant be converted to keto so must convert to a 2˚ this step sets up for oxidation and (facile) ß-keto decarbox in following steps

Answer 31

isocitrate --\> α-ketoglutarate NAD(P)+ -\> NAD(P)H + H⁺ **Isocitrate** **dehydrogenase** **1st** oxidative decarbox. (β-keto) enol intermediate tautomerized to α-ketoglutarate exergonic

Answer 32

**oxidation** of C2 alcohol of isocitrate w/ **reduction** of NAD+ to NADH - followed by β-keto decarbox. of central carboxyl

Answer 33

6-phosphogluconate DH rxn in oxidative phase of PPP

Answer 34

amino acid metabolism

Answer 35

α-KG --\> Succinyl Co-A **α-KG dehydrogenase** CoA-SH, NAD+ **2nd** oxidative decarbox. exergonic

Answer 36

**α-keto decarbox.** uses same enzymes as PDH and cofactors TP, lipoate, FAD **E** released from ox. & decarb. conserved in **NADH** and **succinyl-CoA thioester bond**

Answer 37

2 CO₂ to regenerate OA to complete cycle

Answer 38

Succinyl CoA--\> **Succinate** GDP + Pi -\> GTP + CoA-SH **Succinyl-CoA Synthetase** exergonic

Answer 39

synthesis of GTP thioester cleaved driving **substrate-level phosphorylation** exergonic (barely) Pi acts as Nu allowing CoA-S to leave Pi eventually passed to GDP to form GTP

Answer 40

Succinate --\> Fumarate **Succinate DH (SDH)** prosthetic group: FAD (bound to enzyme) ΔG ~ 0 kJ/mol

Answer 41

enzyme-linked FAD is e acceptor (better acceptor than NAD+) E-FADH2 is reoxidized by coenzyme-Q in ETC this is why it is the only membrane bound enzyme in CAC (embedded in mito. inner membrane allowing it to be part of complex II of ETC) FeS clusters provide direct pathway for e's to ETC leading to synthesis of approx. 1.5 ATP

Answer 42

Fumarate --\> L-malate ***anti-hydration*** (add H2O) - OH and H on opposite side **fumurate hydratase** **stereospecific** (only produces *trans L-malate*)

Answer 43

oxidation of malate (redox) **L-malate** --\> **Oxaloacetate** (regenerated!) endergonic **Malate DH** (reduction of NAD+) reverse rxn in gluconeogenesis (OA malate shuttle)

Answer 44

driven by **mass action** (**product depletion**) - OAA *taken up quickly* in cycle by highly exergonic citrate synthase rxn **[OAA] \< 10^-6M** makes rxn favorable

Answer 45

rxn 1) **Ac-CoA --\> Citrate** rxn 3) **Isocitrate --\>** **α-KG** rxn 4) **α-KG --\> Succinyl-CoA**

Answer 46

molecules that can be converted from **achiral** to **chiral** in a single step

Answer 47

**C**H₃of **pyruvate** & **ac-CoA**

Answer 48

Carbonyl (**C**=O) **C** of **pyruvate** & **ac-CoA**

Answer 49

lost as CO₂during PDH

Answer 50

Conversion of **Succinyl-CoA** to **Succinate** because Succinate symmetrical and the 2 COO- groups (C1 & C4) are **chemically equivalent**

Answer 51

in the second round

Answer 52

methyl C survices 2 complete cycles but 1/2 of whats eft exits cycle on each turn after that 2CO2 that are released during **3rd** round are radiolabeled

Answer 53

accepts e's - gets **reduced**

Answer 54

gives e's - gets **oxidized**

Answer 55

3 NADH 1 ATP 1 FADH₂

Answer 56

metabolic pathway involved in both anabolism and catabolism - much of CAC evolved before aerobes - used for anabolism in anaerobes

Answer 57

**Anaplerotic** reactions that replenish CAC intermediates `

Answer 58

**1) pyruvate + HCO₃^- + ATP \<=^{_{pyruvate carboxylase}}=\> OAA + ADP + Pi** 2) PEP + CO₂+ GDP \<=_{^{PEP carboxylase}}=\> OAA + GTP 3) pyruvate + HCO3- + NAD(P)H \<=^{_{malic enzyme}}=\> malate + NAD(P)⁺

Answer 59

1) substrate availability 2) product inhibition & allosteric feedback inhibition 3) covalent modification

Answer 60

1) PDH complex (pyruvate _^--> ac-CoA) 2) citrate synthase (ac-CoA + OAA ^_--> Citrate) 3) Isocitrate DH (Isocitrate^_--> a-KG) 4) a-KG DH complex (a-KG ^_-->Succinyl-CoA)

Answer 61

substrate availability varies w/ cell metabolic state and [ac-CoA] & [OAA] controls **citrate synthase**

Answer 62

a) high [NADH]/[NAD] can inhibit all **Dehydrogenases** by mass action & NADH competes with NAD+ for binding b) **PDH complex** - ac-CoA competes with CoA for binding to E₂

Answer 63

b) **Citrate Synthase** & **a-KG DH** - by **NADH** and/or **ATP**

Answer 64

**PDH, Isocitrate DH, a-KG DH** - regulated by calcium release of Ca²⁺ stored in sarcoplasmic reticulum induced by neurons (activated by Ca2+) - contraction signal

Answer 65

phosphorylation of PDH E₁ by **pyruvate DH kinases (PDK's)** inactivates enzyme 1) PDK's activated by ATP (signalling excess E) **OR** 2) during low [glucose], glucose required by brain so catabolism blocked in muscle mito by increase PDK activity that phosphorylates & shuts down PDH

Answer 66

signals for FA synthesis inhibition of: PFK-1 converted to ac-CoA & OA by citrate lyase

Answer 67

(high [ac-CoA/citrate/ATP] **favors** glucose & glycogen syntheses inhibition of CAC - accumulates ac-CoA --\> FA synthesis excess ATP inhibits Ox. phosphorylation, NADH accumulates excess pyruvate is converted to glucose (GNG) --\> glycogen synthesis

Answer 68

1) **Glucagon -** low glucose levels 2) **Epinephrine -** need immediate energy

Answer 69

adenyl cyclase is activated, triggering cascade response - cAMP acts as second messenger - activated PKA phosphorylates lipase & perilipin perilipin-P allows lipse-P access to lipid droplet surface - lipase-P converts TAG's to FA's transported by serum albumin to skeletal muscle, heart, kidney enter cells by transporter ß-oxidation to CO₂ yielding ATP

Answer 70

1) free fatty acids 2) glycerol

Answer 71

**ß-oxidation** in mitochondria (in animals)

Answer 72

Carnitine shuttle

Answer 73

activation by acyl-CoA synthetases at OMM

Answer 74

leaving group activation carboxylate ion is adenylated by ATP and PPi is hydrolyzed to 2 Pi CoA-SH thiol attacks, AMP leaves forming fatty acyl-CoA

Answer 75

transfer of acyl-CoA to matrix

Answer 76

fatty acyl group transferred to carnitine by carnitine acyl-transferase I transport : IMS --\> matrix through acyl-carnitine transporter fatty acyl transfer from carnitine back to CoA to regenerate fatty acyl-CoA in matrix

Answer 77

to keep 2 seperate pools of CoA and fatty acyl-CoA (1 in mitochondria, 1 in cytosol) - have different functions

Answer 78

1) biosynthetic (membrane lipids) 2) catabolic (ox. degredation of pyruvate by PDH, FAs, AAs)

Answer 79

carnitine acyltransferase I **malonyl-CoA** is 1st intermediate for **FA synthesis** from **acetyl-CoA** - high [malonyl-CoA] indicates time for FA synthesis & inhibits entry of FAs into mitochondria

Answer 80

adipocytes lack **glycerol kinase** glycerol shuttled to liver via blood & converted to G3P & DHAP for **glycolysis** or **GNG**

Answer 81

1) **oxidative conversion** of 2C units into ac-CoA w/ concomitant generation of NADH 2) **oxidation** **of ac-CoA** into CO₂via CAC w/ concomitant generation of NAD+ & FADH₂ 3) **generates ATP** from NADH & FADH₂ via ETC

Answer 82

every other C is converted to C=O allows Nu attack of CoA-SH each round produces: 1 NADH, 1FADH2, 1 ac-CoA (2 in last round)

Answer 83

dehydrogenation of alkane to alkene by **acyl-CoA DH (AD)** on the IMM FAD = cofactor as e acceptor

Answer 84

hydration of alkene by **enoyl-CoA hydratase** H₂O added across double bond yields alcohol stereospecific - only L

Answer 85

dehydrogenation of alcohol by **ß-hydroxyacyl-CoA DH** NAD = cofactor as hydride acceptor only L-isomers of hydroxyacyl CoA

Answer 86

transfer of FA chain by **acyl-CoA acetyltransferase** carbonyl C in ß-ketoacyl-CoA is electrophilic

Answer 87

succinate DH fumarase malate DH (oxidation of ß **C**H₂to alcohol then carbonyl C=O )

Answer 88

mitochondrial matrix

Answer 89

FA chain elongated by 2C (acetate) units activated donor of 2C units is (3C) malonyl-ACP intermediates are attached to acyl carrier protein (ACP)

Answer 90

formation of malonyl-CoA from ac-CoA & HCO₃^- (1 ATP used) acetyl-CoA + HCO₃^---\> malonyl-CoA catalyzed by **acetyl-CoA carboxylase (ACC)**

Answer 91

1) **NADPH** is used 2) stereochemistry of hydroxylated intermediate is reverse

Answer 92

acetyl-CoA is synthesized in matric IMM is impermeable to acetyl-CoA so acetyl-CoA units are shuttled out of matrix as citrate shuttle also substitutes a NADPH for an NADH which is needed for synthesis

Answer 93

* *compartmentalization -** * **synthesis of TAGs*** - cytosol, liver, adipocytes, intestine ***oxidation to acetyl-CoA -*** mitochondria

Answer 94

rate at which acetyl-CoA is transported into mitochondria by carnitine acyltransferase I

Answer 95

1) allosteric regulation of ACC 2) regulation of gene expression by FAs 3) hormonal regulation of enzymes by covalent mod.

Answer 96

citrate is **positive effector** (feedforward activation) palmitoyl-CoA is **negative effector** (feedback inhibition)

Answer 97

Acetyl-CoA carboxylase **high blood glucose: insulin**: activates Pase, dephosphorylates & activates ACC, malonyl-CoA inhibits ß-oxidation **low blood glucose: glucagon:** activate kinase, phosphorylatres & inactivates ACC, malonyl-CoA not made, **ß-**oxidation to produce ATP , acetyl-CoA to CAC to make more ATP

Answer 98

1) **carnititine acyltransferase 1** & **acetyl-CoA carboxylase**

Answer 99

PFK-1 : inactivates ACC: activates

Answer 100

citrate shuttle xs mitochondrial **ATP** & **acetyl-CoA** increases transport of citrate out of mitochondria to cytosol citrate turns down **glycolysis** in cytosol and switches on **FA biosynthesis** (increases ACC)

Answer 101

malonyl-CoA shuts down **ß-oxidation** 1st intermediate in FA synthesis shuts down transport step (inhibits **carnitine acyltransferase I)** good example of compartmentalization

Answer 102

OAA glycolysis rate is low so supply of precursors for replenishing OAA is cut off and OAA is siphoned off into GNG to maintain blood glucose

Answer 103

Acetyl CoA accumulates in liver mitochondria is converted to ketone bodies: acetoacetate, B-hydroxybutryate & acetone? which are released into bloodstream for organs other than liver (heart, brain) to use as fuels

Answer 104

2 Acetyl-CoA condense to form **acetoacetyl-CoA **(catalyzed by **thiolase**) - reverse reaction in B-oxdn (coA-SH leaves)

Answer 105

addition of another ac-CoA forms HMG-CoA cleaved to form acetoacetate & acetyl-CoA

Answer 106

acetoacetate **reduced **to B-hydroxybutyrate or spontaneously decarboxylated to acetone (exhaled)

Answer 107

water soluble can be transported in blood to other tissues including brain enters CAC or used to make myelin

Answer 108

converted back to acetyl-CoA B-hydroxybutyrate can produce 1 NADH, 2 ac-CoA in CAC & ETC

Answer 109

liver doesnt have B-kat that converts B-hydroxybutryate to acetoacetyl-CoA (then converted to 2 ac-CoA by thiolase)

Answer 110

heart muscle & renal cortex

Answer 111

B-HB will lower pH (ketoacidosis) of blood

Answer 112

to prevent facile B-decarbox. during transport

Answer 113

liver has only limited supply of CoA which is needed for B-oxdn

Answer 114

1) protein turnover 2) high protein diet 3) starvation or untreated diabetes

Answer 115

protein ingestion stimulates **gastrin (hormone) secretion** which stimulates release of **pepsinogen &** **HCl **

Answer 116

**HCl** - denatures proteins (antiseptic) **Pepsinogen** - precursor of pepsin that cuts proteins into peptide fragments & AAs - causes **cholecystokinin** secretion in duodenum

Answer 117

stimulates release of **zymogens** to **pancreas** other proteases are released from pancreas ** **

Answer 118

**secretin **release in blood, stimulating HCO3- (bicarbonate) release to neutralize pH

Answer 119

autoproteolytic cleavave at lower pH (this stimulates secretin to stimulate release of HCO3 to neutralize pH)

Answer 120

to protect **exocrine cells **from **proteolytic attack **

Answer 121

proteases (neutral pH optimum) that are released from pancrease by action of **cholecystokinin **and work in small intestine at neutral pH - activated by proteolytic cleavage

Answer 122

Pancreatic trypsin inhibitor

Answer 123

participate in degrading shorter peptides carboxy and amino terminal ends are removed one at a time free amino acids are transported through intestinal mucosa through blood and to liver

Answer 124

process 1) transamination

Answer 125

**AA** is converted to **a-keto acid** and **a-KG** accepts **amino group** to become **glutamate** (cytosol in mammals)

Answer 126

a-keto acid formed can go to CAC (pyruvate, OAA) glutamate transported to liver mitochondria for **deamination**

Answer 127

**deamination **of glutamate to a-KG in liver mitochondria

Answer 128

ammonia from deamination of glutamate transported as amide N of glutamine

Answer 129

transferred to pyruvate --\> alanine

Answer 130

1) transamination 2) deamination - glutamate dh (ox. deam.) - glutaminase (hydrolyt. deamn) 3) glutamine synthetase

Answer 131

to collect aa groups as l-glutamate from many different aas glutamate functions as amino group donor for biosynthetic pathways or excretion (urea cycle)

Answer 132

bimolecular pingpong 1) amino acid binds, donates amino group to **PLP **& leaves as a-keto acid 2) another a-keto acid binds & accepts amino group from **PLP, **leaves as amino acid * PLP acts as intermediate amino group carrier*

Answer 133

**glutamate DH** glutamate from transamination rxn is transported to mitochondria for ox. deamin. to give **a-KG & NH4+**

Answer 134

only enzyme that can use NAD and NADP at important intersection of C & N metabolism regulated by array of **allosteric effectors**

Answer 135

inhibitors: GTP activators: ADP

Answer 136

**glutamine synthetase** ammonia requires **conversion before transport** from extrahepatic tissues to blood free ammonia + glutamate --\> **glutamine**

Answer 137

1) purine synthesis 2) xs is transported to **liver/kidney **& deaminated by **glutaminase **(in liver mito)

Answer 138

ala can carry NH4+ & carbon skeletons of pyruvate between muscles & liver

Answer 139

**muscle protein** is broken down to **AA** to be used for fuel muscle **aminotranferase **uses **pyruvate** (from glycolysis) as amino acceptor to make **alanine** **Alanine **travels to liver - transamination -\> pyruvate -\> GNG -\> glucose -\> back to muscle amino group from transam back to pyruvate goes to urea cycle

Answer 140

moves pyruvate, lactate, ammonia to liver

Answer 141

transported to liver as amide of glutamine

Answer 142

multiorgan liver and muscle metabolic intermediates

Answer 143

1) secrete 2) recycle 3) excrete uric acid in eggs (solid b/c it precipitates) 4) synthesis of amino acids 5) converted to urea

Answer 144

H2N-(C=O)-NH2 1 NH2 derived from deamin. of glutamine or glutamate in mito through **carbamoyl** **phosphate** other NH2 from aspartate central carbon from bicarbonate also through **carbamoyl phosphate**

Answer 145

look at diagram

Answer 146

1) ammonia - portal vein/bac ox. of aa 2) glutamine - extrahepatic 3) aa's - (glutamate) 3) alanine (muscle)

Answer 147

ATP + Bicarbonate (HCO3-): **LG activation ** bicarbonate is phosphorylated ammonia displaces P group to make carbamate carbamate phosphorylated to yield **carbamoyl-P**

Answer 148

enters in urea cycle with **ornithine** to make **citrulline** ornithine + carbamoyl-P --\> citrulline + Pi

Answer 149

citrulline is transported out of matrix to cytosol

Answer 150

***arginosuccinate synthetase *** carbonyl of citrulline attacks AMP of ATP - LG=PPi addition of aspartate to citrullyl-AMP - LG=AMP activation of ureido oxygen of citrulline sets up addition of aspartate to form arginosuccinate

Answer 151

link b/w urea cycle & CAC

Answer 152

In urea cycle: OAA -\> asp -\> fumarate (in cytosol) -goes into mitochondria to form 1 NADH when converted to OAA

Answer 153

NH4+ + HCO3- + aspartate + 3ATP --\> urea + fumarate + 2ADP + AMP + 4Pi

Answer 154

2 for carbamoyl-P and 1 for citrullyl-AMP

Answer 155

**Aspartate ** **- **needed for cytosolic conversion of **citrulline** to **arginosuccinate ** - produced when **OAA **accepts amino group from **glutamate** **fumarate **to **OAA **produces 1 NADH *Glutamate DH rxn *also produces 1 NAD(P)H (glu--\> a-KG) (1 NADH = 2.5 ATP)

Answer 156

CAC intermediates Ac-CoA

Answer 157

1) diverted to GNG (forming glucose) 2) diverted to ketogenesis (formation of ketone bodies) 3) completely oxidized to CO2 & H2O

Answer 158

most cases of genetic defects in aa metabolism lead to defective neural development & mental retardation - most aa's are neurotransmitters, precursors, antagonists

Answer 159

Phe hydroxylase mutation Phe may compete w/ other amino acids for transport across blood brain barrier

Answer 160

Phe + pyruvate --\> Phenylpyruvate + alanine **(aminotransferase)** phenylpyruvate --\> phenylacetate + phenyllactate all 3 products build up in tissues, blood & urine

Answer 161

limiting Phe intake to levels barely adequate to support growth Tyrosine is an essential nutrient for individuals with PKU must be supplied in their diet

Answer 162

1) cytosol 2) cytosol 3) mito. matrix 4) cytosol (except one rxn in lumen of ER) 5) mitochondria 6) cytosol

Answer 163

ATP synthesis & electron transport are coupled by H+ gradient across mito membrane

Answer 164

1) flow of e's through **membrane-bound carriers ** 2) **exergonic** e flow couples to **endergonic** H+ transport against [c] gradient 3) **H+ transport** **down** [c] gradient through specific **protein channels** provides E for ATP synthesis 4) **ATP synthase** couples **H+ flow** to **ADP phosphorylation**

Answer 165

1) Ubiquinone (coenzyme Q) 2) cytochrome 3) iron-sulfur proteins

Answer 166

hydrophobic, lipid-soluble benzoquinone + isoprenoid side chain - shuttles e through the membrane (**lateral** **diffusion**) carries both e- & H+

Answer 167

proteins with iron-containing heme prosthetic groups reduction potential depends on heme environment (aa's surrounded - electrostatic effects)

Answer 168

a & b: loosely associated with enzyme c: covalently linked (prosthetic) coenzyme

Answer 169

integral membrane proteins peripheral membrane proteins associated through electrostatic interactions w/ the IMM outer surface (on side of IMS)

Answer 170

contain iron-sulfur clusters (1 e transfer) at least 8 in mito ETC reduction potential

Answer 171

Complex : I - NADH DH II - Succinate DH (in CAC) III - Ubiquinone: cyt c oxidoreductase cytochrome c1 IV - cytochrome oxidase

Answer 172

1) complex 1 : FMN -\> Fe-S --\> Q 2) Complex II- Succinate oxidized Fumarate: FAD --\> Fe-S --\> Q 3) Fatty acyl-CoA -\> Enoyl CoA : FAD-\> FAD-\> FAD, Fe-S 4) cytosolic G3P to G3PDH

Answer 173

**NADH DH ** **NADH Ubiquinone oxidoreductase** transfers e's from NADH to ubiquinone coupled rxns: a) **exergonic: **NADH + H⁺_N+ Q --\> NAD+ +QH2 b) **endergonic: **vectorial translocation of 4H+ (per 2e) **matrix (N side)** becomes **-ve**; **IMS (P side)** becomes **+ve** charged proton gradient QH2 diffuses laterally to complex II

Answer 174

**Succinate to Ubiquinone** **(****succinate - FAD - Fe-S - ubiquinone (Q--\>QH2))** complex includes succinate DH - only membrane bound enzyme of CAC not a proton pump

Answer 175

other substrates of DHs (i.e. **acyl coA DH **) can pass electrons to ETC through ubiquinone fatty acyl-CoA --\> enoyl CoA (1st step in ß-ox)

Answer 176

binding sites: **succinate, ubiquinone** bound: **FAD, FeS clusters, hemes** **heme *b*** is **not** in **direct path** of e transfer but thought to **prevent** **leakage** of e's & conversion of H2O2 to oxygen **radicals** that will damage tissue

Answer 177

cyt bc1 complex - transfers e's from ubiquinol (QH2) to cyt c a) **exergonic: **QH2 + cytc(ox) --\> Q + cytc(red) b) **endergonic: **translocation of 4H+/2e

Answer 178

cyt c (soluble) heme accepts e's from complex III and moves to complex III

Answer 179

space inside complex in which Q is free to move from N side of membrane to IMS as it shuttles e- & H+ across IMM

Answer 180

**QH2** donates **1 e- to cyt c1** (via rieske)and the **other to Q **(via cyt. b) 2H+ are pumped in this 1st half of the Q cycle semiquinone radical formed another **QH2 **donates** 1e to** another **cyt c1 **and the other to **semiquinone (Q radical) **(also 2H+ to form QH2) this pumps another 2H+ to IMS (Pside)

Answer 181

QH₂ + 2cytc₁ (**oxidized**) + 2H⁺_N ==\> Q + 2cytc₁ (**reduced) **+ 4H⁺_P

Answer 182

*first*, Q on N side is **reduced **to semiquinone radical in *second stage, *semiquinone radical is further **reduced **to QH₂ on P side: 2 molecules of QH₂are oxidized to Q releasing 2H⁺ per Q (4 overall) into IMS (Pside) Each QH₂donates: 1e to cyt c1 (via rieske Fe-S center) 1e to Q near N side (via cyt b) - uses 2H+ per Q taken from matrix

Answer 183

***cytochrome oxidase*** since it transfers e's from **cyt c** to **oxygen** **exergonic: **4cyt_red + 4H⁺_N + O₂=\> 4cyt(_ox)+ 2H₂O **endergonic: **translocation of 1H+ per 1e (4H⁺_N --\> 4H⁺_P) overall: 4cyt_red+ 8H⁺_N + O₂ =\> 4cyt_(ox) + 4H⁺_P+ 2H₂O **copper **& **heme **bound proteins are involved in e transport

Answer 184

e's reach **Q **through **complexes I & II ** r**educed Q (QH₂)** serves as mobile carrier of e's & protons - passes e's to **complex III **which passes them to cyt c (mobile link) **complex IV **transfers e's from **reduced cyt c **to O₂

Answer 185

e flow through **complexes I, III & IV **are accompanied by **proton flow** from **matrix **to **IMS **

Answer 186

**Complex I: **4H⁺ **Complex III: **4H+ **Complex IV: **2H+ from **matrix (N)** to **IMS (P) ** ***OVERALL***: 10H⁺_P

Answer 187

NADH + 11H⁺_N+ 1/2O₂→ NAD⁺ + 10H⁺_P + H₂O

Answer 188

ATP synthesis & electron transport are coupled by electrochemical gradient across mito. membrane

Answer 189

spontaneous (**exergonic**) e transfer through complexes I, III & IV is coupled to non-spontaneous (**endergonic**) H⁺ pumping from matrix H+ pumping creates **electrochemical gradient, ***proton-motive force* a **membrane potential **(-ve in matrix) & **pH gradient** (alkaline in matrix)

Answer 190

proton motive force consists of both: **membrane potential **& **pH gradient **

Answer 191

**non-spon. ATP synthesis** coupled to **spont. H+ transport** into matrix **pH & electrical gradients** created by respiration = driving force for H+ uptake H+ returns to matrix via Fo uses up pH & electrical gradients

Answer 192

∆G = RT ln (C2/C1) C1 \< C2 , ∆G \> 0

Answer 193

side of **lower solute **concentration until eq. is achieved

Answer 194

movement of ion without a counterion results in **endergonic **seperation of +ve and -ve charges, producing **electrical potential**

Answer 195

**electrochemical potential: **the sum of chemical & electrical gradients ∆G_t= RT ln (C2/C1) + ZF∆ψ

Answer 196

a combination of **chemical conc. difference (C2/C1) ** and the **electrical potential (Vm) **across the membrane net ion movement continues until electrochemical potential = 0

Answer 197

energy stored as proton gradient protons can flow spontaneously down **electrochemical gradient, **and energy is available for work (ADP --\> ATP)

Answer 198

movement of ions across selectively permeable membrane, down electrochemical gradient

Answer 199

**oxidation & phosphorylation **become obligately coupled (absence of one inhibits the other)

Answer 200

IMM is impermeable to H+ H+ can only reenter the matrix through **proton-specific channels (Fo) **

Answer 201

**proton-motive force **that drives H+ back into matrix **F1 complex** associated with **Fo**

Answer 202

no electron transport no proton gradient produced shuts down ATP synthesis

Answer 203

no ATP produced no release of proton gradient & PMF builds up since high [H+] build up is not dissipated, free energy released by oxidn of substrates is not enough to pump any more protons against steep gradient shut down of electron transport

Answer 204

uncoupled by **uncoupler**

Answer 205

1) ETC and 2) proton gradient with ATP synthesis

Answer 206

a chemical **uncoupler** of **oxidative phosphorylation ** - has a **dissociable proton** & very **hydrophobic**

Answer 207

**carries** protons across IMM, **dissipating** proton gradient

Answer 208

a) slight increase in slope b) nothing

Answer 209

a) increase b) increase

Answer 210

a) rate of consumption decreases so slope is same as beginning (slowed) b) horizontal line (no ATP synthesis)

Answer 211

DNP disrupts proton gradient (dissipates) uncouples a) increases b) stays the same (no ATP synthesis - horizontal line)

Answer 212

isolated mito. are first incubated in pH 9 buffer containing **0.1 M KCl **so matrix **reaches eq**. w/ surroundings (KCl & buffer leak into mito) then resuspended in pH 7 buffer containing **valinomycin **& **no KCl** change in buffer creates a different of 2 pH unites across IMM. outward flow of K+ (carried by valinomycin) down conc. gradient without counterion Cl- creates **charge imbalance across membrane **(matrix = -ve) sum of **chemical potential by pH difference **& **electrical potential by seperation of charges **is a PMF large enough to support ATP synthesis in absence of oxidizable substrate

Answer 213

F-type ATPase

Answer 214

large enzyme complex 2 functional domains : **F1 & Fo**

Answer 215

catalyzes ATP synthesis from ADP + Pi

Answer 216

allows H+ to passively diffuse from P to N side **(proton pore)** ## Footnote **o** = oligomycin sensitive

Answer 217

F1 = **ATPase** Fo becomes **H+ pore**

Answer 218

reversiblity & enzyme stabilization ## Footnote ¹⁸O exchange experiment showed that when F1 is incubated with ATP & H₂¹⁸O , the Pi contained 3-4 of the ¹⁸O, indicating that **both ATP hydrolysis & synthesis have occured several times during** reaction is reversible & exchange doesnt require input of energy

Answer 219

a) 10⁵ b) 2.4 ATP synthase **stabilizes** ATP relative to ADP + Pi by binding more ATP more tightly, releasing enough E to counterbalance cost of making ATP

Answer 220

**conformational** change of F1 proton gradient requires Fo

Answer 221

release of ATP from enzyme (not formation of ATP)

Answer 222

tight binding of ATP provides sufficient binding energy to bring the free energy of E-bound ATP close to that of ATP & Pi so reaction is **readily reversibleb** eq constant near zero

Answer 223

proton-motive force (**PMF**)

Answer 224

a3b3yde subunit y = **shaft **that passes through Fo & associates with only 1 B subunit

Answer 225

a) 1 **catalytic site** for ATP synthesis v) adopts **3 different conformations**

Answer 226

i) empty (associated with y) ii) binds ADP iii) binds ATP

Answer 227

composed of 3 subunits (ab2c10-12) all **transmembrene proteins** mostly **alpha-helical**

Answer 228

shaft made up of F1 subunits y & e

Answer 229

cylinder & shaft rotate, & B subunits of F1 change conformation as Y subunit associates with each in turn

Answer 230

3 active sites of F1 take turns catalyzing ATP synthesis ADP & Pi are bound -\> conformation change new structure tightly binds ATP 2nd conformational change reduces affinity

Answer 231

proton diffusion through Fo, causing c subunites and attached y subunit to rotate. contact with B subunit forces releae of ATP

Answer 232

cooperative conformational change in which **B-ATP site is converted to B-empty conformation** and ATP dissociates **B-ADP site is converted to B-ATP conformation**, promoting **condensation** of bound ADP + Pi to **form ATP** **B-empty site becomes B-ADP site **which loosely binds **ADP + PI **entering from solvent

Answer 233

used in **liver, heart & kidney** for transporting reducing equivalents from cytosolic NADH into mito matrix

Answer 234

**NADH in cytosol** enters IMS through **outer membrane** (porins) passes **2e to OAA forming malate. ** **malate crosses IMM** and passes **2+ to NAD+** (resulting NADH oxidized by ETC) **OA formed** cannot pass into cytosol so **transaminated to aspartate** and leaves via glu-asp transporter then **OAA is regenerated in cytosol from asp **completing cycle

Answer 235

alternative means of moving reducing equivalents (e-) from cytosol to matrix in **skeletal muscle & brain**

Answer 236

in cytosol, DHAP accepts 2 e from NADH (catalyzed by **cytosolic glycerol-3-p DH) ** isozyme of g3p DH bound to outer face of IMM transfer 2e from glycerol-3-p in IMS to FAD then ubiquinone (Q)

Answer 237

regulated by availability of **ADP** when mass action ratio [ATP]/[ADP][Pi] drops (meaning more ADP available - rate of ATP synthesis **increases**

Answer 238

regulation by **cellular energy needs** ## Footnote **co-ordinate regulation**

Answer 239

relative [ATP] & [ADP] controls electron transfer, ox. phos., CAC & glycolysis

Answer 240

1) rate of e transfer & ox phos. **increase ** 2) rate of pyruvate ox. (via CAC) is **enhanced**, **increasing flow of e's **into ETC 3) rate of glycolysis is **enhanced **& supplies more pyruvate

Answer 241

interlocking of **glycolysis (cytosol) **and **CAC (mito) **by **citrate **which inhibits **glycolysis **

Answer 242

citrate accumulates within mito, then tranported to cytosol when both [ATP] & [citrate] rise, they produce a **concerted allosteric inhibition of PFK-1 **that is greater than the sum of their individuals effects, slowing glycolysis

Answer 243

**product inhibition: **G6P **activation **by Pi

Answer 244

**activated **by: AMP, ADP **inhibited by: **ATP, citrate

Answer 245

activated by: ADP inhibited by: ATP, NADH

Answer 246

activated by: **ADP, AMP, NAD+** inhibited by: **ATP, NADH**

Answer 247

product inhibition by citrate activated by: ADP inhibited by: ATP, NADH

Answer 248

activated by: ADP inhibited by: ATP

Answer 249

product inhibition by **succinyl-CoA ** inhibited by: ATP, NADH

Answer 250

phosphorylation/oxidation ratio amount of ATP produced from oxygen reduced amounge of ATP produced from movement of 2e- through ETC

Answer 251

10 H+ pumped out per NADH 6 H+ pumped out per FADH2 3 H+ flowed in through Fo/F1 per ATP 1H+ used in transporting ATP, ADP, Pi across IMM 10/4 = 2/5 ATP per NADH 6/4 = 1.5 ATP per NADH

Answer 252

major storage of glucose in animals

Answer 253

takes place in **all tissues **but predominantly in **liver cytosol **

Answer 254

cant be catabolized anaerobically

Answer 255

1) broken down for distribution to other tissues (**liver**) 2) broken down for **glycolytic fuel **to produce **ATP** (**muscle) **

Answer 256

branched to make it more soluble & creating more non-reducing ends that are available for polymerization & breakdown

Answer 257

when [glucose] & [ATP] are **high**

Answer 258

first, glucose is primed by a) glucokinase (**liver**) b) hexokinase (**muscle**)

Answer 259

g6p is isomerized by **phosphoglucomutase ** g6p --\> g1p

Answer 260

glucose is charged with UDP by **UDP-glucose pyro-phosphorylase ** sugar-P + NTP =\> NDP-sugar + 2Pi

Answer 261

sugar nucleotides are suitable for polymerization Anomeric of sugar activated by attachment to nucleotide through phosphate ester linkage

Answer 262

1) net reaction gives large -ve free E change & charges synthetic rxn 2) nucleotide contributes to binding sites for enzymes (**glycogenin & glycogen synthase**) reducing Ea 3) nucleotidyl group facilitates Nu attack by activating the sugar anomeric C (UDP is good LG, leaving group activation) 4) nucleotides act as tags for different processes (glycogen synthesis vs glycolysis)

Answer 263

glucose is transferred to non-reducing end of branched glycogen by **glycogen synthase ** free E change from G1P to glycogen polymer is highly favorable - non-reducing end of glycogen acts as Nu and attacks C1 of UDP-glucose, UDP is LG

Answer 264

block of residues is transferred to make a1-\>6 linkage from growing a1-\>4 chain by **glycogen branching enzyme**

Answer 265

C0hain: a1-\>4 Branch points: a1-6 once **11 residues **are built up, **6-7 residues **are transferred to a branch

Answer 266

increases **solubility & # of non-reducing ends **

Answer 267

initial attack by OH group of Tyr¹⁹⁴on C-1 of glucosyl moiety of UDP-glucose results in **glucosylated Tyr residue** C1 of another UDP-glucose molecule is now attacked by C-4 hydroxyl group of terminal glucose and this sequence repeats to form beginning glycogen molecule (primer) of 8 glucose residues attached by **(a1-\>4) ****glycosidic linkages**

Answer 268

starting at center of glycogenin molecule, glycogen chains **(12-14 residues) **extend in tiers. Inner chains have **two (a1-\>6) branches each**. Chains in outer tiers are **unbranched. ** **12 tiers** in mature glycogen particle consisting of **~55,000 glucose residues **

Answer 269

**glycogen phosphorylase **using **Pi **to form **glucose-1-P **

Answer 270

oxygen of Pi attacks anomeric C of non-reducing end forming G1P process continues until enzyme is 4 glucose units away from branch

Answer 271

the **glycogen branching enzyme **removes branch

Answer 272

1) to **keep inside** 2) to **save ATP **

Answer 273

**glycogen phosphorylase **uses Pi to form G1P until 4 glucose units away from branch point **debranching enzyme **transfers 3 of glucose residues from branch point to chain **(transferase activity)** **debranching enzyme** removes 1 glucose residue of branch point **(a1--\>6 glucosidase activity)**

Answer 274

**phosphoglucomutase **converts G1P to G6P that **muscle - **can enter glycolysis **liver - **converted to glucose by G6Phosphatase for release to blood (GNG)

Answer 275

reciprocal regulation by **phosphorylation by cAMP dependant pathway ** synthase - **less active** phosphorylase - **more active**

Answer 276

phosphorylase a **phosphatase (PP1) **dephosphorylates - **less active (b) ** phosphorylase b **kinase **phosphorylates - **more active (a) **

Answer 277

**phosphorylase b kinase **activated by **glucagon (liver) **and **epinephrine, **Ca2+, AMP (**liver**)

Answer 278

phosphorylated by **GSKinase ** (inactive) dephos. by **PP1 **(active)

Answer 279

GSK3 phosphorylates to make **b conformation** **insulin inhibits GSK3 **

Answer 280

PP1 makes glycogen synthase **a conformation **(active) **activated by: **insulin*, G6P, glucose (forward activation)* **inhibited by: **glucagon, epinephrine

Answer 281

muscle liver

Answer 282

glucose & glycogen synthesis/breakdown

Answer 283

adrenaline (mobilizing fuel) stress leads to fight or flight response epinephrine released **increases BP, heart beart, ****dilation of resp. pathways** increases O2 delivery & uptake in tissues acts on muscle, adipose, liver in cAMP dependant pathway that **inactivates **glycogen synthase and **activates **glycogen phosphorylase (increasing glucose release)

Answer 284

1) binds ## Footnote 2) conformational change -\> GTP binds G_sa subunit (replaces GDP) 3) Gsa associates with **adenyl cyclase ** 4) cAMP formation (catalyzed by adenyl cyclase) 5) activation of PKA 6) phosphorylation of other proteins (kinases) by PKA

Answer 285

blood glucose levels

Answer 286

**epinephrine regulation (**via **cAMP) **to promote **glycogen breakdown **& inhibit **glycolysis **while stimulating **GNG & glucose release (liver) **

Answer 287

glucose uptake & storage/consumption

Answer 288

FAs & carbs make up **main storage **fuels in adipocytes & muscle, respectively aa's & nucleic acids contribute to functional & informational macromolecules

Answer 289

a chemical released by a cell or gland in one part of the body that sends out messages that affects cells in other parts of the organism

Answer 290

ATP stored E (fat, glycogen, creatine phosphate) must first be converted to ATP before body can actually use it

BIOC 221 - Midterm #2 (advanced editor) Flashcards

(317 cards)