BIOC 212 Lecture Notes - Lecture 47: Dehydrogenation, Mitochondrial Matrix, Beta Oxidation
29 May 2018
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Metabolism IX
Pyruvate to Acetyl CoA
• In aerobic conditions, pyruvate from glycolysis turned into acetyl-CoA instead of
lactate
o Funnels carbons into the next metabolic step of cell cycle; citric acid cycle
• Pyruvate is turned into acetyl-CoA by the pyruvate dehydrogenase complex
o Pyruvate metabolized by large enzyme complex
o Major regulatory funnel from glycolysis into the energy-generating oxidative
metabolism pathway
o Major regulatory step
• Pyruvate decarboxylase (A) first removes the carboxyl group to make a 2-carbon
acetyl group
o First enzyme of the complex
o Removes CO2 from pyruvate molecule
• Same mechanism for further removal of carbon for when cell utilizes
acetyl-CoA
• Carboxylic acids are relatively labile substrates --if the carboxylic acid's acidic
oxygen's electrons attack the carbon, the entire group will leave as carbon
dioxide
o Happens naturally in the bloodstream, CO2 can interchange to become
HCO3-
o Specific enzymes that help dissolve CO2 in blood by doing this
• This is essentially the same reaction reverse
o A lot of the enzymes involved in handling of carbons in metabolism just
catalyze the removal of CO2 to generate short 2C compounds that can then
be fed into the citric acid cycle
o Get further reduced back down to zero carbons at the end of that cycle
• Lipoamide reductase-transacetylase (B) then conjugates the acetyl group to
CoA-SH
o Second enzyme in the complex
o When decarboxylate pyruvate and form an acetyl group, it covalently binds
to new acetyl group
• Binds the new acetyl group and hands it off to CoA
o Lots of enzyme use CoA; thiocysteine side arm co-factor from protein to
hand it off to the CoA SH
• Higher reactivity in the protein-substrate bond than in the CoA
substrate bond
• Higher reactivity in CoA-substrate bond than in the next metabolic
substrate in the chain
