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Pyruvate Oxidation:
Pyruvate Dehydrogenase and the TCA Cycle
Aerobic “respiration” in mitochondria: important for ATP synthesis
and a source of intermediates for other biochemical pathways
pyruvate (C3H3O3) + 4 NAD+ + FAD + GDP + Pi + 2H2O
3 CO2 + 4 NADH + 3 H+ + FADH2 + GTP
First step: pyruvate dehydrogenase
Pyruvate dehydrogenase complex
Classic multienzyme complex: 3 enzyme proteins
5 cofactors: TPP, CoA-SH, lipoic acid, NAD +, FAD
Pyruvate dehydrogenase complex
Classic multienzyme complex: 3 enzyme proteins
5 cofactors: TPP, CoA-SH, lipoic acid, NAD +, FAD
functional
groups
Pyruvate dehydrogenase function
Animation:
http://www. brooksco le.com/chemistry_d/templates/st udent_resources/sha red_resources/ animations/pdc/pdc.html
Acetyl-CoA is oxidized in the citric acid (Kreb’s, TCA) cycle
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
TCA Cycle
Recap TCA cycle:
acetyl-CoA(C2H3O-CoA) + 3 NAD+ + FAD + GDP + Pi + 2H2O
CoA-SH + 2 CO2 + 3 NADH + 3 H+ + FADH2 + GTP
Include pyruvate oxidation:
pyruvic acid(C3H4O3) + 4 NAD+ + FAD + GDP + Pi + 2H2O
3 CO2 + 4 NADH + 4 H+ + FADH2 + GTP
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•
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Complete oxidation of the pyruvate carbons
Reduction of 4 NAD+ and one FAD
Phosphorylation of one GDP
The TCA cycle is a source of biosynthetic precursors
But what happens when intermediates are removed from the cycle?
Without intermediates, the cycle stops!
“Anaplerotic” reactions replenish the intermediates.
Pyruvate + CO2 + ATP + H2O
OAA + ADP + Pi + 2 H+
A modification of the TCA cycle (glyoxylate cycle) lets plants and bacteria
make carbohydrates from fats.
to glucose
Q uickTim e™ and a
TI FF ( Uncom pr essed) decom pr essor
ar e needed t o see t his pic t ur e.
isocitric lyase
malate synthase
Summary
•The TCA cycle gives complete oxidation of the pyruvate carbons.
•And reduction of 4 NAD+ and one FAD.
•And phosphorylation of one GDP.
•The TCA cycle is a source of biosynthetic precursors.
•Pyruvate carboxylase and the glyoxylate cycle replenish precursors
•Replenishment of NAD + and FAD are also essential.