BIOLCHEM 415 1st Edition Lecture 19 Outline of Last Lecture I. Introduction to the Pyruvate Dehydrogenase (PDH) complexOutline of Current Lecture II. Introduction to the Citric Acid CycleIII. There are 8 enzymatic steps in the CACIV. Regulation of enzymes in CACCurrent LectureCitric Acid Cycle- Kreb’s Cycle/Tricarboxylic Acid Cycle- occurs in the mitochondrion- aerobic respiration- uses acetyl CoACellular Aerobic respiration- pyruvate mitochondrial matrix acetyl CoA Citric Acid Cycle- acetyl CoA 1 ATP + 2 CO2 + 8e-- electrons go into the electron transport chain- each pyruvate oxidized into about 13 ATP- about 28 ATP total from the citric acid cycle/oxidative phosphorylation- net about 30 ATP from 1 glucoseCitric Acid Cycle- 8 enzymatic steps (focus on the energy generating steps)- citrate synthaseThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- “beginning”- oxaloacetate condensed with acetyl CoA produces citryl CoA- hydrolysis of citryl CoA produces citrate- induced fit enzyme (means conformation change occurs)- Aconitase- isomerization of citrate- dehydration of citrate produces cis-aconitase - hydration of cis-aconitase produces iso-citrate- allows for oxidation reaction- Isocitrate dehydrogenase- NADH is produced- intermediate: oxalosuccinate - produces α-ketoglutarate- decarboxylation- α-Ketoglutarate dehydrogenase complex- α-ketoglutarate succinyl CoA- homogulous to pyruvate dehydrogenase- oxidation- produces NADH- Succinyl CoA Synthase- phosphorylation of ADP ATP- succinyl CoA succinate- can also convert GDP to GTP (dependent on form)- mechanism1) phosphate group (enzyme) attacks carbonyl group2) phosphate histidine side chain3) ADP binds4) ATP produced- Succinate dehydrogenase and fumarase- FADH2 produced by succinate dehydrogenase- fumarate is the intermediate- turned into malate- Malate dehydrogenase- NADH produced- malate oxaloacetate- “last” step- for each acetyl CoA- 3 NADH : (oxidative phosphorylation) about 2.5 ATP/NADH- 1 FADH2 : (oxidative phosphorylation about 1.5 ATP/FADH2- 1 ATP- table 19.1 in the notes is useful- NADH and FADH2 are important in the electron transport chainRegulation of the Citric Acid Cycle- ATP and pyruvate inhibit PDH kinase- ATP, acetyl CoA, and NADH inhibit PDH complex- Ca2+ stimulates PDH phosphatase- citrate inhibits PFK (from glycolysis)- Isocitrate dehydrogenase- inhibited by ATP and NADH- stimulated by ADP- α-ketoglutarate dehydrogenase complex- inhibited by ATP, succinyl CoA, and NADHCitric Acid Cycle intermediates Biosynthetic precursors- citrate fatty acids- α-ketoglutarate various amino acids- succinyl CoA heme, chlorophyll, etc- oxaloacetate glucose, amino acids- replenishing them1) pyruvate carboxylase- maintain flux through citric acid cycle2) fatty acid degradation- generates acetyl CoA and enters Citric Acid CycleCitric Acid Cycle and Cancer- mutation in succinate dehydrogenase and fumarase- defects accumulate- accumulation = inhibition of prolyl hydroxylase 2- inactivates hypoxia inducible factor 1 ( HIF-1)- stimulates expression of glycolysis enzymes- produces 2-hydrocygluterate instead of
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