Citric acid cycle

• in mitochondrial matrix

• operated under aerobic conditions

Citric acid cycle

• 6 NADH

• 2 FADH2

• 2ATP

• 4 co2

• supply intermediates for gluconeogensis - amphibolic(catabolic and anabolic)

• regenerate oxalaocetate

total products

• include pyruvate (from glycolysis) and from oxidation of fatty acids

• coenzyme

• CoA incorporates a nucleotide, a water soluble vitamin (pantothenic acid) and a reactive

Acetyl CoA

• allows pyruvate to enter mitochondria matrix

Pyruvate translocase

• Pyruvate formed during glycolysis need to be transported to the mitochondria if aerobic conditions

• Pyruvate enters the mitochondria via pyruvate translocase

Glycolysis to TCA cycle

• adds acetyl-CoA to oxaloacetate to for citrate

1. Citrate synthase

• addition of water

• coverts citrate to isocitrate

2. Acontitase

• converts isocitrate to a-ketoglutarate

• forms carbon dioxide and NADH

3. Isocitrate dehydrogenase

• a-ketogluatate converted to succinyl-CoA

• forms carbon dioxide and NADH

4. a-ketoglutarate dehydrogenase

• succinyl coA to succinate

• forms ATP

Succinate thiokinase

• forms FADH2

• converts succinate to fumarate

succinate dehydrogenase

• fumarate to malate

• forms water

fumarase

• malate to oxaloacetate

• forms NADH

Malate dehydogenase

• 3 enzymes channelling substrates between them for the pyruvate to acetyl coA reaction

• 2 regulatory enzymes - PDH kinase and PDH phosphatase

• needed for thiamine pyrophosphate

• lack of vitamin B1 — reduces PDH activity, increase pyruvate, decrease ATP

• site of arsenic poisioning - reduce pdh activity, decrease ATP

pyruvate dehydrogenase reaction

• turns it off when high NADH and NAD+, ATP to ADP and acetyl coA to coA ratios phosphatase turns on when reverse is true

PDH kinase

• turns on when reverse is true

• tight regulation

PDH phosphtase

• inner mitochondiral membrane

• impermeable to NADH

• two shuttle mechanisms take place to transfer the electrons from NADH

NADH shuttles (ETC)

• transfers electrons from cytoplasmic NADH to mitchondrial FAD

• produced 1.5 ATP for each cytoplasmic NADH

Glycerophosphate shuttle

• transfer electrons from cytoplasmic NADH to mitochondrial NAD+

• produces 2.5 ATP for each cytoplasmic NADH

• more effici ent

Malate-aspartate shuttle

• substrate avaliability

• alter enzyme activity - ratios of products, fedback effectors, hormones

• alter pyruvate dehydorgenase activity and acetyl coA supply

• obligatory coupling with oxidative phosphorylation - high energy state leads to decrease in activity of cycle. low energy - increase activity

Citric acid regulation

• pyruvate converted to acetyl coA

• hydrogen ions picked up by NAD+

• co2 is released

prep for TCA