Robinson Lectures 1,2,3

Front 1

Thiamin active form, and enzymes it is cofactor for

Back 1

B 1
thiamin pyrophosphate
-pyruvate dehydrogenase
-alpha-ketoglutarate dehydrogenase
-transketolase (in PPP)

Front 2

Diseases related to thiamin deficiency

Back 2

Beriberi
Wernicke-Korsakoff Syndrome (in chronic alcoholics)

Symptoms- peripheral neuropathy, fatigue, ataxia, mental confusion, loss of eye coordination

Front 3

Why does thiamin deficiency cause neurological symptoms?

Back 3

The brain uses glucose as its source of fuel and by aerobic metabolism only, so interrupting aerobic breakdown of glucose (by preventing it from being converted into pyruvate) affects the brain

Front 4

Riboflavin- precursors for?

Back 4

B2
flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD)

Front 5

Niacin- precursor for?

Back 5

B3
NAD and NADP
work on malate/lactate dehydrogenases

Front 6

What AA can be converted into niacin? What does niacin deficiency result in?

Back 6

Tryptophan
depression, dermatitis, diahrrea
assoc. w/pellagra

Front 7

What else is niacin used for?

Back 7

given to lower LDL/raise HDL cholesterol

Front 8

How many electrons/protons do NAD and FAD carry?

Back 8

FAD carries two e-, two H+ (FADH2)

NAD carries two e-, one H+ (NADH + H)

Front 9

Panthothenic Acid

Back 9

B5
req'd for synthesis of coenzyme A

Front 10

Structure of CoA?

Back 10

adenine, ribose, PP, pantothiene

Front 11

CoA function? Where is active site located?

Back 11

carrier of acyl groups and fatty acids

terminal sulfhydryl group is reactive site- acyl groups linked here through thioester bond

Front 12

TCA cycle importance

Back 12

final common path for generation of energy through oxidation of fuel molecules
most of ATP generated by cells is by conversion of pyruvate to CO2 in TCA, and production of NADH and FADH2

Front 13

Two stages of conversion of pyruvate to CO2 and H2O

Back 13

1. 2 pyruvate--> acetyl CoA via pyruvate dehydrogenase

2. Oxidation of acetyl-CoA to CO2 in TCA cycle

Front 14

3 enzymes involved in PDH complex

Back 14

pyruvate dehydrogenase
dihydrolipoyl transacetylase
dihydrolipoyl dehydrogenase

Front 15

Coenzymes associated with pyruvate dehydrogenase

Back 15

TPP (tightly bound)

Front 16

coenzymes w/dihydrolipoyl transacetylase

Back 16

lipoic acid (tightly bound)
Coenzyme A (carrier of products)

Front 17

coenzymes w/dihydrolipoyl dehydrogenase

Back 17

FAD (tightly bound)
NAD (carrier of products)

Front 18

Step 1 of PDH rxn

Back 18

PDH (E1) decarboxylates pyruvate, and the remaining acetyl group is bound to TPP on E1 (to form acetyl/hydroxyethyl TPP)

Front 19

Step 2 of PDH rxn

Back 19

2 carbon acetyl group is transferred from acetyl-TPP to lipoic acid (the coenzyme of lipoyl transacetylase- E2)

Front 20

Step 3 of PDH rxn

Back 20

acetyl group transferred from lipoamide to coenzyme A to form acetyl-CoA. lipoamide is left in reduced state (two SH groups)

Front 21

Step 4 of PDH rxn

Back 21

Lipoamide disulfide is reoxidized by dihydrolipoyl dehydrogenase (E3) with FAD as cofactor to generate FADH2

Front 22

Step 5 of PDH rxn

Back 22

FADH2 is oxidized by NAD to form NADH + H. NADH will then be oxidized in e- transport chain of mitochondria

Front 23

PDH kinase

Back 23

inactivates PDH by phosphorylating it

Front 24

Activators of PDH kinase

Back 24

ATP, NADH, Acetyl-CoA

Front 25

Inactivators of PDH kinase

Back 25

ADP, NAD, CoA-SH, pyruvate

Front 26

PDH phophatase

Back 26

removes phosphate from PDH making it more active

Front 27

Dysfunctions in PDH complex result in?

Back 27

neurological symptoms (other tissues can use FA/AA for fuel, neural tissue uses only glucose)
Increased levels of pyruvate and lactate (and perhaps lactic acidosis if enough accumulates in blood)

Front 28

What part of PDH complex does beriberi occur?

Back 28

At E1- b/c no TPP

Front 29

Where does arsenic poisoning affect PDH complex?

Back 29

As binds sulfhydryls, preventing reoxidation -- acyl group can't bind

Front 30

Genetic defects in PDH complex

Back 30

similar symptoms to beriberi
usu. due to E1 deficiency

Front 31

Pacemaker of TCA cycle?

Back 31

citrate synthase
has large neg. delta G, so drives the cycle forward
(hydrolysis of thioester bond yields lots of E)

Front 32

Regulators of IDH (isocitrate dehydrogenase)?

Back 32

NADH, ATP (negative allosteric effectors)

Front 33

What is meant by TCA is amphibolic pathway?

Back 33

contains both anabolic and catabolic processes

Front 34

TCA intermediates that can be used in lipid biosynthesis:

Back 34

acetyl CoA is primary source of carbons for FA and cholesterol.

Citrate serves as source of Acetyl CoA-- can't travel out of inner mitochondrial membrane on its own, so travels as part of citrate (and then converted via ATP citrate lyase)

Front 35

TCA intermediates that can be used for gluconeogenesis?

Back 35

malate and oxaloacetate

Front 36

TCA intermediates for AA synthesis?

Back 36

alpha-ketoglutarate can be converted to glutamate

oxaloacetate can be converted to aspartate

Front 37

TCA intermediates for porphyrin biosynthesis?

Back 37

succinyl-CoA is precursor for the heme group

Front 38

Anaplerotic rxns

Back 38

Used to replenish supply of oxaloacetate if other intermediates are used up in biosynthetic rxns

Front 39

pyruvate carboxylase
fxn, what activates it, what's its coenzyme

Back 39

converts pyruvate + HCO3 + ATP--> oxaloacetate + ADP

activated by acetyl-CoA, b/c if there's an oxaloacetate deficit, Acetyl-CoA builds up

Biotin is necessary- carries CO2

Front 40

Transamination anaplerotic rxns

Back 40

glutamate--> alpha-ketoglutarate

aspartate--> oxaloacetate

Front 41

Standard reduction potential

Back 41

the tendency of a chemical species to lose or acquire electrons

Front 42

Favorable reduction reactions pos or neg delta E?

Back 42

positive (and thus a negative delta G)

Front 43

Equation of redox rxns?

Back 43

G=-nFE

Front 44

What is a cytochrome? What form is Fe in? What are cytochromes a,b,c like?

Back 44

A protein w/a tightly bound heme group. Fe can either be in Fe+2 or Fe+3 form. A,B cytochromes are integral membrane proteins. C is smaller, more mobile

Front 45

Complex I: protein component and prosthetic groups

Back 45

NADH CoQ oxidoreductase
FMN, Fe-S

Front 46

Complex II

Back 46

succinate CoQ oxidoreductase
FAD, Fe-S, heme b

Front 47

Complex III

Back 47

CoQ cytochrome C reductase
cytochromes b and c, Fe-S

Front 48

Complex IV

Back 48

cytochrome c oxidase
Cu2+, heme a

Front 49

Amytal

Back 49

inhibits complex I between flavoprotein and ubiquinone

Front 50

Rotenone

Back 50

inhibits transfer of e- in complex I from Fe-S to ubiquinone

Front 51

Antimycin A

Back 51

blocks chain at complex III
produced by streptomyces bact
ingredient in fintrol

Front 52

Cyanide

Back 52

blocks complex IV by binding to iron in the Fe-S complexes of cytochrome C oxidase

Front 53

CO and sodium azide

Back 53

also inhibit complex IV

Front 54

proton motive force

Back 54

refers to chemical (more H+s on one side) and electrical (separation of charge- more positive on outside) gradients generated by pumping of protons during ETC

Front 55

ATP synthase structure

Back 55

Fo portion - protons pass through, rotate around C ring, and finally back into matrix

F1 portion- 3alpha 3 beta subunits that don't rotate

beta have binding sites for ADP+P

Front 56

ATP synthase function

Back 56

As H+ attach to Cs in ring, the ring rotates causing conformational changes in beta binding sites
open- ADP + P attach
loose- ADP/P bound loosely
tight- conversion to ATP
open- ATP leaves, another ADP+P enter

Front 57

How many protons required for ATP synthesis?

Back 57

4 per ATP
so NADH can produce ~3ATP,
FADH2 can produce ~2ATP

Front 58

G3P shuttle

Back 58

dihydroxyacetone picks up 2Hs from NADH+H to form G3P. G3P dehydrogenase reoxidizdes G3P to dihydroxyacetone and transfers e- to FAD to make FADH2 on inside of mitochondria. This is not as efficient, since an NADH is replaced by an FADH2, which enters the ETC later

Front 59

Malate-aspartate shuttle

Back 59

OAA + NADH-->NAD + malate
malate passes through membrane
Malate-->OAA + NADH via malate dehydrogenase
OAA gains amino group from glutamate, forming aspartate and alpha ketoglutarate. Aspartate travels through membrane, and is then converted back to OAA

Front 60

UCP1

Back 60

mitochondrial membrane uncoupler - found in brown fat of mammals, involved in heat production during hibernation

Front 61

2,4 dinitrophenol

Back 61

uncoupler at inner mitochondrial membrane

Front 62

oligomycin

Back 62

ATP synthase inhibitor, works at Fo portion