TCA cycle

Question 1

4 sources of acetyl-CoA

Answer 1

pyruvate (glycolysis)
acetoacetate (ketone body)
acetate (ethanol)
palmitate (fatty acid)

Question 2

how is acetyl-CoA formed from acetate?

Answer 2

acetyl-CoA synthase

Question 3

what are the 2 types of acetyl-CoA synthase?

Answer 3

type1- liver, cytosol, used in FA synthesis

type2- heart/mm, mito matrix, feeds into TCA cycle

Question 4

regulation of citrate synthase

Answer 4

inhibited: citrate

Question 5

fates of excess citrate (3)

Answer 5

• inhibition of citrate synthase
• inhibition of phosphofructokinase-1
• conversion to fatty acid in cytosol by citrate lyase

Question 6

MOA of aconitase

Answer 6

responsible for the conversion of citrate to isocitrate, contains iron-sulfur cluster, will shift OH from C3 to C2 so that first decarobylation can occur

Question 7

describe the structure of a-ketoglutarate dehydrogenase

Answer 7

3 different enzyme complexes

Question 8

describe E1 of a-ketoglutarate dehydrogenase

Answer 8

carries TPP and performs decarboxylation = CO2 leaves

Question 9

describe E2 of a-ketoglutarate dehydrogenase

Answer 9

transfers 4C from a-ketoglutarate/TPP to CoASH with lipoic acid = succinyl-CoA forms

Question 10

describe E3 of a-ketoglutarate dehydrogenase

Answer 10

transfers electrons from lipoid acid to FAD and then to NAD+ = NADH

Question 11

what enzyme converts GTP to ATP?

Answer 11

nucleoside diphosphate kinase

Question 12

MOA of succinate dehydrogenase

Answer 12

converts succinate to fumarate by removing double bond and transferring electrons to FAD to yield FADH2

Question 13

what is unique about succinate dehydrogenase?

Answer 13

embedded in inner mito membrane, part of ETC, FADH2 is covalently attached via histidine, has iron-sulfur cluster that transfers electrons from FADH2 to coenzyme Q

Question 14

fumarase deficiency

Answer 14

rare, AR, one of the only d/o of the TCA cycle enzymes that is not fatal “polygamists downs”

Question 15

what is the high energy bond in acetyl-CoA and succinyl-CoA?

Answer 15

thioester bond with the acyl group

Question 16

what makes the formation of acetyl-CoA favorable?

Answer 16

oxidative decarboxylation of pyruvate by pyruvate decarboxylase when pyruvate is acetly-coA source, other acetly-CoA sources use splitting of CC bonds

Question 17

2 endergonic steps of TCA cycle

Answer 17

citrate- isocitrate (+1.5)
malate - oxaloacetate (+7.1)
still TCA cycle is -13.1 overall

Question 18

alternative use for citrate

Answer 18

fatty acid synthesis

Question 19

alternative use for a-ketoglutarate

Answer 19

amino acid synthesis, neurotransmitters (glutamate, GABA)

Question 20

alternative use for succinyl-CoA

Answer 20

heme synthesis (contended with glycine to form d-aminolevulinic acid)

Question 21

alternative use for malate

Answer 21

gluconeogenesis

Question 22

alternative use for oxaloacetate

Answer 22

amino acid synthesis

Question 23

what type of reactions will act to replenish TCA intermediates that have been extracted for other uses?

Answer 23

anapleurotic reactions= involve breakdown of amino acids to replenish all of the 4C intermediates that are removed

Question 24

what is catapleurosis?

Answer 24

removing the TCA intemediates for biosynthesis (reverse of anepleurosis which is replenishing them)

Question 25

what 3 aa are used to synthesize pyruvate?

Answer 25

serine, threonine, alanine

Question 26

how can pyruvate be converted to oxaloacetate?

Answer 26

add CO2, ATP with pyruvate carboxylase and biotin = oxaloacetate

Question 27

what 3 aa can be used to synthesize glutamate?

Answer 27

histidine, arginine, proline

Question 28

how is glutamine converted to a-ketoglutarate?

Answer 28

direct transamination

Question 29

what 3 aa can be used to form propionyl-CoA?

Answer 29

isoleucine, valine, methionine

Question 30

what 2 aa can be used to form fumarate?

Answer 30

phenylalanine and tyrosine

Question 31

action of citrate lyase

Answer 31

when citrate accumulates, citrate lyase converts citrate to acetyl-CoA and oxaloacetate hat can then be used for fatty acid synthesis

Question 32

rate limiting step of TCA cycle

Answer 32

conversion of a-ketoglutarate to succinyl-CoA by a-ketoglutarate dehydrogenase

Question 33

where is pyruvate dehydrogenase complex located?

Answer 33

mitochondrial matrix

Question 34

describe the structure of the pyruvate dehydrogenase complex

Answer 34

3 catalytic units | 2 regulatory units

Question 35

3 catalytic units of pyruvate dehydrogenase complex

Answer 35

E1- dehydrogenase with TPP- removes CO2 E2- transacetylase with lipoamide- forms acetyl-CoA E3- dehydrogenase with FAD- forms NADH

Question 36

2 regulatory units of pyruvate dehydrogenase complex

Answer 36

1- PD kinase- phosphorylates serine and inhibits, + acetyl-CoA and NADH, - pyruvate 2- PD phosphatase- removes phosphate from serine to activate PD, + Ca

Question 37

where is the m/c place to have a defect in PDHC?

Answer 37

E1

Question 38

why is E3 of PDHC unique?

Answer 38

E3 gene is shared by a-ketoglutarate dehydrogenase

Question 39

MOA of dichloroacetate

Answer 39

treatment for PDHC deficiency that works by inhibiting PD kinase, thereby increasing PDHC activity

Question 40

what 2 enzymes will be affected by thiamine deficiency?

Answer 40

a-ketoglutarate dehydrogenase and pyruvate dehydrogenase bc they both need TPP as a cofactor in E1

Question 41

how will arsenic and mercury affect PDHC and a-ketoglutarate dehydrogenase?

Answer 41

bind to sulfhydryl groups in the lipoamide and inactive it, treat with competitive inhibitor that 2,3-dimercaptopropanol (BAL)