Lecture 11 and 12 Citric Acid Cycle (CAC) and Tricarboxylic Cycle (TCA)/Kreb’s Cycle

when does the citric acid cycle run

when oxygen is present

does the citric acid cycle use oxygen

no

where does the citric acid cycle occur

in the mitochondria

importance of acetyl-coenzyme A

• allows the body to sense what is happening

• interconnects biomolecule metabolism

  • AA and fatty acids can be broken into acetyl-co A

what is the substrate and product that regenerates itself in the CAC

acetyl-co A

where does the majority of the CO2 in the body come from

the citric acid cycle

how much ATP does 1 FADH molecule produce?

1.5 ATP molecules

how much ATP does 1 GTP equate to

1 ATP molecule

how much ATP does 3 NADH produce

2.5 ATP

how much energy does the CAC produce

1 energy molecule and the rest are potential energy molecules

energy from CAC compared to glycolysis

CAC produces more ATP/energy than glycolysis

overview of the CAC

multistep catalytic process that converts acetyl groups derived from carbs, fatty acids, and amino acids to CO2, and produces NADH, FADH2, and GTP

how many reactions and enzymes are involved in the synthesis of acetyl-co A

5 different reactions using 3 different enzymes

what does the pyruvate dehydrogenase (PDH) complex allow for

tight control, system wants to go pyruvate → acetyl-co A

what does arsenic do to PDH activity

inhibit it

why does arsenic inhibit the PDH complex

the reduced lipomide can bond to arsinite, forming an unbreakable bond, causing inability to oxidize lipoamide, so no more ATP can be made

what is thiamine pyrophosphate (TPP)

cofactor bound to E1 of PDH, decarboxylates pyruvate, yielding a hydroxyethyl-TPP carbanion

what is lipoic acid

cofactor that is covalently linked to a Lys on E2 (lipoamide), accepts the hydroxyethyl-carbanion from TPP as an acetyl group

what is coenzyme A

cofactor that is a substrate for E2, it accepts the acetyl group from lipoamide

what is flavin adenine dinucleotide (FAD)

cofactor bound to E3 that is reduced by lipoamide

what is nicotinamide adenine diculeotide (NAD+)

cofactor that is located as substrate for E3 and is reduced by FADH2

what are the 5 cofactors required for the PDH complex

TPP, lipoamide, coenzyme A, FAD, and NAD+

PDH complex

a multienzyme complex that catalyzes a five-part reaction in which pyruvate releases CO2, and the remaining acetyl group becomes linked to coenzyme A

reaction 1 of CAC

• Substrate: ACOA

• Enzyme: Citrate Synthase

• Product: Citrate

reaction 2 of CAC

• Substrate: Citrate

• Enzyme: cis-Aconitate

• Product: Isocitrate

reaction 3 of CAC

• Isocitrate Dehydrogenase, Releases 1st CO2, NAD+-Dependent Oxidation Produces 1st NADH

  • Substrate: Isocitrate

  • Enzyme: Isocitate Dehydrogenase

  • Product: alpha-Ketogluterate

reaction 4 of CAC

• α-Ketoglutarate Dehydrogenase Resembles PDH Complex—2nd NADH

  • Substrate: alpha-Ketogluterate

  • Enzyme: alpha-Ketogluterate dehydrogenase

  • Product: Succinyl-Co A

reaction 5 of the CAC

•  Succinyl-Co A Synthetase Produces GTP

  • Substrate: Succinyl-Co A

  • Enzyme: Succinyl-Co A Synthetase

  • Product: Succinate

reaction 6 of the CAC

•  Succinate Dehydrogenase Produces FADH2

  • Substrate: Succinate

  • Enzyme: Succinate Dehydrogenase

    • Malonate Competitively inhibits succinate dehydrogenase

  • Product: Fumarate

what competitively inhibits succinate at the succinate dehydrogenase enzyme

malonate

reaction 7 of the CAC

• Substrate: Fumarate

• Enzyme: Fumarase

• Product: Malate

reaction 8 of the CAC

•  Malate Dehydrogenase Produces 3rd NADH

  • Substrate: Malate

  • Enzyme: Malate Dehydrogenase

  • Product: Oxaloacetate

overview of the reactions of the CAC

eight enzymes of the CAC catalyze condensation, isomerization, oxidation-reduction, phosphorylation, and hydration reactions

what does TCA stand for

Tricarboxylic Acid Cycle or the Krebs Cycle or the Citric Acid Cycle

products of the CAC

two reactions produce CO2, one reaction produces GTP, and 4 reactions generate the reduced coenzymes NADH or FADH2