Carb Metabolism II

Question 1

PDH Complex

Answer 1

• forms acetyl CoA mitochondrial matrix
• exergonic
• inhibited by acetyl CoA and NADH

1) PDHase: oxidize pyruvate, yield CO2, 2 Cs bind covalently to TPP coenzyme
2) DHLTAase: 2C molecule of TPP oxidized and transferred to lipoic acid a coenzyme covalently bonded to enzyme, disulfide group acts as oxidizing agent creating acetyl group now bonded to lipoid acid via thioester linkage, catalyzes CoA-SH interaction w thioester link forming acetyl coa and lipoic acid left reduced

3) DHL dehydrogenase: FAD used as coenzyme to reoxidize lipoid acid, FAD~>FADH2, both lipoic acid and NADH replenished

Question 2

B-oxidation

Answer 2

• cytosol
• thioester bond formed between CoA-SH and carboxyl group of FA
• activated fatty acyl-CoA transferred to carnitine to cross inner mitochondrial membrane
• acyl-CoA formed and B-ox occurs to form acetyl-CoA

Question 3

AA catabolism

Answer 3

• amino group lost in transamination and carbon skeletons used to synthesize ketones

Question 4

ketones

Answer 4

when PDH complex inhibited reverse rxn forms acetyl CoA

Question 5

alcohol

Answer 5

alcohol/acetaldehyde dehydrogenase helps to form acetyl CoA

when accompanied by NADH buildup, FA synthesis

Question 6

TCA

Answer 6

• mitochondrial matrix
• coupling of molecule acetyl-CoA to OAA
• GTP and NADH and FADH2 produced
• requires oxygen so electron carriers don’t build up and inhibit

Question 7

Net results and ATP yield of PDH and TCA

Answer 7

4 NADH~>10 ATP (2.5 ATP/NADH)
1 FADH~>1.5 (1.5 ATP/FADH2)
1 GTP~>1 ATP

Total: 12.5 ATP/pyruvate = 25 ATP/gluc

since glycolysis yields 2 ATP and 2 NADH, another 7 ATP and 30-32 thus far

Question 8

PDH complex regulation

Answer 8

• PDH kinase
• when ATP rises, phosphorylation of PDH inhibits acetyl-CoA production
• PDH complex reactivated by PDH phosphatase in response to high ADP levels

Question 9

checkpoints of TCA cycle

Answer 9

• citrate synthase: ATP, NADH, citrate, and succinyl-CoA inhibitory
• isocitrate dehydrogenase: inhibited by ATP and NADH, activated by ADP and NAD+
• α-ketoglutarate dehydrogenase complex: succinyl-CoA, NADH, ATP inhibit, stimulated by ADP and Ca2+

Question 10

Key enzymes and rxns of TCA

Answer 10

1) citrate synthase couples actual CoA and OAA and forms citrate and CoA-SH
2) aconitase isomerizes citrate to isocitrate
3) isocitrate dehydrogenase oxidizes and decarboxylates isocitrate to form a-ketoglutarate, rate limiting step, generates CO2 and NADH
4) a-KG dehydrogenase complex act like PDH complex to form a-KG and succinyl-CoA generating second CO2 and NADH
5) succinyl-CoA synthetase hydrolyzes the thioester bond in succinyl-CoA to form succinate and CoA-SH to generate 1 GTP
6) succinate dehydrogenase oxidizes succinate to form fumarate, 1 FADH2 generated
7) Fumarase hydrolyzes alkene bond of fumarate forming malate
8) malate dehydrogenase oxidizes malate to OAA and 3rd and final NADH generated

Question 11

ETC chain

Answer 11

• inner mitochondrial matrix facing matrix
• NADH donates electrons and reduction potentials inc until oxygen receives electrons
• Complex I: transfer e- from NADH to FMN and then to CoQ, 4p+
• Complex II: transfer e- from succinate to FAD and then to CoQ, no proton pumping
• Complex III: transfer e- from CoQ to heme, forming cytochrome c, 4p+
• Complex IV: cytochromes and Cu2+ to form water, 2p+

NADH crosses inner mitochondrial membrane via G3P forming FADH2 using DHAP or malate-aspartate

Question 12

F0

Answer 12

ion channel

Question 13

F1

Answer 13

ADP~>ATP powered by gradient