Citric Acid Cycle + Reading 5

BIOC13

Citric acid cycle generates mainly ___ and is (aerobic/anaerobic)

High energy electrons and is anaerobic

Oxidative phosphorylation generates mainly ___ and is (aerobic/anaerobic)

ATP and is aerobic

Cataplerotic reactions

drain the citric acid cycle

Anaplerotic reactions

replenish the citric acid cycle

First of citric acid cycle

Condensation of acetyl group with oxaloacetate to form citrate

Stage 2 of citric acid cycle

Regeneration of oxaloacetate

Step 1

Oxaloacetate + acetyl (from CoA) = citrate

Intermediate in step 1

Citryl CoA

How is citrate synthase selective

Induced fit: oxaloacetate binds first to cause conformational change to fit acetyl group, and formation of citryl CoA causes change to result in correct positioning for hydrolysis

Step 2

Aconitase swaps OH and H groups of citrate to make isocitrate

Intermediate in step 2

cis-aconitase

Step 3

Isocitrate dehydrogenase catalyzes oxidative decarboxylation of Isocitrate to α-ketoglutarate, generating NADH

Step 4

α-ketoglutarate dehydrogenase complex catalyzes the synthesis of succinyl CoA from α-ketoglutarate, generating NADH

Step 5

Succinyl CoA synthetase catalyzes cleavage of the thioester of succinyl CoA, powering formation of ATP

Intermediate in step 5

High phosphoryl transfer potential phosphorylated enzyme intermediate

Step 6

Succinate dehydrogenase (in inner mitochondrial membrane) reduces FAD to FADH₂ by oxidizing succinate to fumarate

Why is FADH₂ and not NADH formed in step 6

Free energy is not enough to reduce NAD⁺

Step 7

Fumarase hydrates fumarate to L-malate

Step 8

Malate dehydrogenase regenerates oxaloacetate from L-Malate, generating NADH

Citric acid cycle net reaction

acetyl CoA + 3 NAD⁺ + FAD + ADP + P_i + 2 H₂O → 2 CO₂ + 3 NADH + FADH₂ + ATP + 2 H⁺ + CoA

Allosteric control points

Isocitrate dehydrogenase and α-ketoglutarate dehydrogenase

Pyruvate carboxylase effect on citric acid cycle

Replenishes by making oxaloacetate

Acetyl-CoA is a (positive/negative) regulator of citric acid cycle

positive

High citrate makes (glycolysis/gluconeogenesis) favorable

gluconeogenesis

Glyoxylate cycle

Plants and bacteria convert fat into carbohydrates

Glyoxylate cycle net reaction

2 acetyl CoA + NAD⁺ + 2 H₂O → succinate + 2 CoASH + NADH + 2 H⁺

Glyoxylate cycle enzymes

Isocitrate lyase and malate synthase

Leptin

Released by adipocytes to report on fat storage

Incretin effect

Oral glucose causes a greater insulin response than IV injection of glucose

GLP-1

Glucagon-like peptide 1

GIP

Gastric inhibitory peptide

GLP-1 effects on metabolism

Enhances insulin production and decreases hunger

Difference between GIP and GLP-1

GIP released sooner after a meal, is more sensitive to fat and has a greater effect on fat metabolism

When oxygen levels are high, HIF-1α is (active/inhibited/degraded)

degraded

Important post-translational modification regarding HIF-1α in normoxia (ubiquitination/glycosylation/phosphorylation)

ubiquitination

Ubiquitination of HIF-1α causes

Degradation in the proteasome

Regulation of HIF-1 transcriptional activator

Specific prolines in HIF-1α are hydroxylated in normoxia, which lets VHL bind and cause ubiquitination and proteasomal degradation

Hypoxia stabilizes HIF-1, which goes to nucleus and

Increases GLUTs, glycolytic enzymes, PFK2/FBPase2, lactate dehydrogenase, PDK, VEGF, etc.