BIOC 2300 Lecture Notes - Lecture 19: Pyruvate Dehydrogenase, Acetyl-Coa, Citric Acid Cycle

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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
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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.

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