Citric acid cycle

Steps of citric acid cycle

Acetyl CoA+ oxaloacetate ←> citrate ←> cis aconitate ←> isocitrate ←> a ketoglutarate ←> succinyl coA ←> succinate ←> fumarate ←> malate ←> oxaloacetate

pyruvate

acetyl coA

a keta glutarate

Oxaloacetate

citrate

Cis aconitate

Isocitrate

a keto glutarate

succinyl coA

succinate

fumarate

L malate

CAC produces

3 NADH, 1 FADH2, 1 GTP (ATP)

Energy per NADH

2.5 ATP

Energy per FADH2

1.5 ATP

Pyruvate → acetyl coA reactants and enzyme?

Enzyme: pyruvate dehydrogenase complex (E1+E2+E3)

CoA-SH

NAD+ →NADH

TPP, lipoate, FAD

E1 of the PDH complex

Pyruvate dehydrogenase: transfers CH3-C=O to TPP, lose CO2

E2 of the PDH complex

Dihydrolipoyl transferase

transfers -CHOH-CH3 to oxidized lipolysine

—then add CoA-SH, form acetyl CoA

E3 of PDH complex

Dihydrolipoyl dehydrogenase

reduced lipolysine + FAD →oxidized (S-S) lipolysine + FADH2

FADH2 + NAD+ →FAD + NADH + H+

Reactants and enzyme for oxaloacetate+acetyl coA

Citrate synthase

• Input H2O

• output: CoA-SH

Citrate →cis aconitate →isocitrate enzymes, input, output

Enzyme: aconitase

Input: H2O

Output: H2O

Isocitrate → a keto glutarate enzyme, input, output

Enzyme: isocitrate dehydrogenase

Input: NAD+

Output: NADH+H+, CO2

Which reactions lose CO2?

isocitrate → a keto glutarate

a keto glutarate → succinyl CoA

a keto glutarate →succinyl CoA enzyme, input, output

Enzyme: a ketoglutarate dehydrogenase complex

Input: CoA-SH, NAD+

Output; NADH + CO2

Succinyl Coa →succinate enzyme, input, output

succinyl CoA synthetase

Input:GDP + P

Output: GTP, CoA-SH

Succinate →fumarate enzyme, input, output

Enzyme: succinate dehydrogenase

Input: FAD

Output: FADH

fumarate → malate enzyme, input, output

Enzyme: fumarase

Input: OH-, H+

L Malate → oxaloacetate enzyme, input, output

Enzyme: L malate dehydrogenase

Input: NAD+

Output: NADH, H+

Which reactions reduce NAD+ to NADH?

isocitrate →a keto glutarate

a keto glutarate →succinyl coA

L malate→oxaloacetate

Which reaction reduces FAD to FADH2?

succinate → fumarate

Which reaction produces GTP

succinyl coA →succinate

Deaminated aspartate —>

Oxaloacetate

Deaminated glutamate —>

a keto glutarate

Amphibolic

Both catabolic and anabolic

Which organisms can convert acetate to carb?

bacteria, fungi, protist, plants

**Animals can’t convert acetate/acetyl coA to carbs

in the CAC, there is ____ conversion of acetate to oxaloacetate

no net conversion

Anaplerotic reactions

chemical reactions that replenish intermediates

Ways oxaloacetate is replenished

1. Pyruvate + HCO3- + ATP ←> oxaloacetate + ADP + Pi

2. PEP + CO2 + GDP ←> oxaloacetate + GTP

3. PEP + HCO3- ←> oxaloacetate + P

Which enzyme catalyzes pyruvate ←>oxaloacetate

pyruvate carboxylase

What enzyme (s) catalyze PEP ←> oxaloacetate

1, PEP + CO2 + GDP ←> oxaloacetate + GTP (PEP carboxykinase)

2. PEP + HCO3- ←> oxaloacetate + P (PEP carboxylase)

How is malate regenerated

Pyruvate + HCO3- + NADH ←> malate + NAD+

w malic enzme

Pyruvate carboxylase

catalyzes the reversible carboxylation of pyruvate by HCO3- to form OAA

• most important anaplerotic rxn in mammalian liver, kidney, adiapose

How is pyruvate carboxylated regulated

Req energy from ATP

allosterically activated by acetyl coA

Where is the CAC regulated?

PDH complex

citrate synthase

isocitrate dehydrogenation complex

a keto glutarate dehydrogenation complex

How is the PDH complex regulated?

Inhibited: ATP, acetyl coA, fatty acids, NADH

Activated: ADP, CoA, NAD+, Ca2+

How is citrate synthase regulated?

Inhibited: ATP, NADH, succinyl coA, citrate

Activated: ADP

How is isocitrate dehydrogenase regulated

Inhibited: ATP

Activated: Ca2+, ADP

How is alpha ketoglutarate dehydrogenase complex regulated

Inhibited: succinyl coA, NADH

Activated: Ca2+

What is PDH kinase

Inhibits the PDH through phosphorylation

• is activated (PDH inactive) when products of PDH complex (ATP, NADH, A-coA)

• inhibited (PDH active) when substrates of PDH complex (ADP, NAD+, pyruvate)

What is PDH phosphatase

Reverses PDH kinase inhibition by removing phosphate

Difference between PDH kinase and PDH phosphatase

PDH kinase inhibits PDH complex when activate

PDH phosphatase reverses PDH complex inhibition