BIOC 2300 Lecture Notes - Lecture 19: Pyruvate Dehydrogenase, Acetyl-Coa, Citric Acid Cycle
Citric Acid Cycle
March 2, 2016
Pyruvate: anaerobic fermentation, aerobic oxidation, anaplerotic carboxylation
• Aerobic – mitrocondrial conversion of pyruvate to acetyl-CoA and oxidation in TCA
• Anaerobic: cytosolic regeneration of NAD+
The citric acid cycle is the final part of the oxidation of nutrients to CO2
• All nutrients broken down to acetyl-CoA
• Cycle oxidizes acetyl-CoA to CO2 and reduces NAD+ and FAD to NADH and FADH2
• …….
The oxidation of pyruvate to acetyl-CoA and the TCA cycle reactions take place in the mitochondria
• compartmentation
o allows additional regulation of metabolic pathways
o brings metabolites of one pathway to closer vicinity faster reaction, less risk of
unwanted side reaction
• no mitochondria – no citric acid cycle
• all metabolites for cycle must be imported into mitochondria
Oxidation of pyruvate to acetyl-CoA
• catalyzed by pyruvate dehydrogenase
• pyruvate + NAD+ + CoASH Acetyl-CoA + NADH + CO2 + H+
• requires:
o NAD+ (vitamin B3)
o TPP (B1)
o FAD (B2)
o CoA-SH
o Lipoic acid
• The oxidation of pyrivate to acetyl-CoA is irreversible
• Acetyl-CoA cannot be converted to glucose
• Pyruvate glucose via gluconeogenesis
Coenzyme A
• Derivative of ADP, panthenic acid linked it via a phosphate ester bond
• Attached to pantothenic acid is a mercaptoethylamine group
• The thiol group can form thioester bonds which are more reactive than carboxylesters
coexyme A can transfer acyl groups
• CoASH = CoA with a –SH group
• Activated form of acetate
• Can enter several pathways:
o Oxidation in TCA
o Precursor for larger metabolites
Enzyme activity can be regulated by phosphorylation: regulation of Pyruvate dehydrogenase (PDH)
• {DH is allosterically inhibited by acetyl-CoA and NADH (product inhibition)
• PDH kinase phosphorylates PDH and inactivates PSH
• PDH phosphatase dephosphorylates PDH and activates PDH
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Pyruvate: anaerobic fermentation, aerobic oxidation, anaplerotic carboxylation: aerobic mitrocondrial conversion of pyruvate to acetyl-coa and oxidation in tca, anaerobic: cytosolic regeneration of nad+ The citric acid cycle is the final part of the oxidation of nutrients to co2: all nutrients broken down to acetyl-coa, cycle oxidizes acetyl-coa to co2 and reduces nad+ and fad to nadh and fadh2. Enzyme activity can be regulated by phosphorylation: regulation of pyruvate dehydrogenase (pdh: {dh is allosterically inhibited by acetyl-coa and nadh (product inhibition, pdh kinase phosphorylates pdh and inactivates psh, pdh phosphatase dephosphorylates pdh and activates pdh. The citric acid cycle: mitochondrial generation of reducing units for oxidative phosphorylation, condensation of acetyl coa and oxaloacetate, reduction od nad+ and fad. Steps to citrate cycle: citrate synthase: condensation of oxaloacetate with acetyl-coa to citrate. Irreversible: aconitase: isomerization of isocitrate by dehydration-hydration. Kgdh is sensitive to thiamine deficiencies: succinyl-coa synthetase. Thioester is higher energy bond (hydrolysis makes gtp) Gtp easily converted to atp: succinate dehydrogenase.