biochem exam 3 #2: pyruvate dehydrogenase + TCA

why can’t pyruvate enter TCA cycle directly

pyruvate = 3C, TCA needs 2C

mnemonic for pyruvate dehydrogenase reaction

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Pyruvate + CoA + NAD+ → AcetylCoA + CO2 + NADH + H+

what is significant about the pyruvate dehydrogenase step

its a commitment; once you convert pyruvate to acetyl-CoA, it commits the molecule to the TCA

function of E1 in pyruvate dehydrogenase complex

removes CO2 from pyruvate

function of E2 in pyruvate dehydrogenase complex

adds CoA to two carbon molecule to make AcetylCoA

function of E3 in pyruvate dehydrogenase complex

reduces NAD+ into NADH

primary cofactor(s) of E1 and function

TPP → stabilizes two carbon fragment

primary cofactor(s) of E2 and function

Lipoamide → carrier of 2C molecule
CoA → forms acetyl CoA

primary cofactor(s) of E3 and function

FAD and NAD+ → FAD transfers electrons to NAD+, forming NADH

where are many PDH cofactors derived from

B vitamins

allosteric inhibitors and activators of PDH

inhibitors: high energy signals, such as NADH and Acetyl-CoA
activators: low energy signals, such as ADP and pyruvate

covalent modification of PDH

inactivated by phosphorylation, activated by dephosphorylation

result of impaired PDH

pyruvate converted to lactate, can result in lactic acidosis

where is the TCA cycle located

in mitochondrial matrix

description of primary phases of TCA

1) entry

• acetyl-coa + oxaloacetate → citrate

2) oxidation

• carbon molecules are oxidized, 2CO2, 2NADH

3) ATP generation

• substrate level phosphorylation

4) oxaloacetate regeneration

mnemonic for TCA

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citrate, isocitrate, a-ketoglutarate, succinyl coa, succinate, fumarate, malate, oxaloacetate

step 1 of TCA + enzyme

acetyl coa + oxaloacetate → citrate

enzyme: citrate synthase

step 3 of TCA + enzyme

isocitrate → a-ketoglutarate

enzyme: isocitrate dehydrogenase

step 4 of TCA + enzyme

a-ketoglutarate

enzyme: a-ketoglutarate dehydrogenase

significance of steps 3 and 4 in TCA

oxidation; release of 2 NADH + 2 CO2

what is the energy yield per one turn of the TCA cycle

3 NADH, 1 FADH2, 1ATP, 2 CO2

what is the energy yield per one glucose

6 NADH, 2 FADH2, 2 ATP, 4 CO2

regulation of citrate synthase

inhibited by NADH + ATP
high energy signals will turn off enzyme

regulation of isocitrate dehydrogenase

inhibited by ATP and NADH

activated by ADP and Ca+

regulation of a-ketoglutarate dehydrogenase

inhibited by succinyl-coa, ATP, and NADH

significance of oxidation reactions within TCA cycle

oxidation must be coupled with reduction: NAD+ → NADH
- electron carriers NADH and FADH2 can be used in ETC