CHAPTER TWELVE: THE PYRUVATE DEHYDROGENASE COMPLEX
1) Intro
a) plays a central role in intermediary metabolism
i) point of convergence in the degradation of a variety of important
biomolecules
b) Complex’s reactions take place in mitochondria, highly oxidative, and
intermediates are tightly bound to the complex.
c) three noncovalently linked enzyme complex
i) pyruvate dehydrogenase (E1)
ii) lipoate acetyltransacetylase (E2)
iii) lipoamide dehydrogenase (E3)
d) contains between 1 and 3 copies of two regulatory enzymes, a kinase and a
phosphatase.
e) requires five cofactors
i) thiamine pyrophosphate
ii) lipoic acid
iii) flavin adenine dinucleotide
iv) Coenzyme A
v) NAD+.
f) Benefits of multi enzyme complex
i) improvement in catalytic efficiency
ii) coordinated catalysis
iii) increased overall reaction rate
iv) minimum of side reactions.
2) Cytoplasmic Pyruvate Must Enter the Mitochondria
a) Glycolytic pathway only partial use of glucose molecule
b) Complete oxidation of pyruvate to C02 and H20 occurs during Citric Acid Cycle
in mitochondria
i) Symport Mechanism
(1) pyruvate translocase transports the pyruvate molecule through the inner
mitochondrial membran
(2) OH or H+ exits
ii) pyruvate dehydrogenase complex converts pyruvate to acetyl-SCoA
(1) highly exergonic rxn
(2) irreversible
1) Intro
a) plays a central role in intermediary metabolism
i) point of convergence in the degradation of a variety of important
biomolecules
b) Complex’s reactions take place in mitochondria, highly oxidative, and
intermediates are tightly bound to the complex.
c) three noncovalently linked enzyme complex
i) pyruvate dehydrogenase (E1)
ii) lipoate acetyltransacetylase (E2)
iii) lipoamide dehydrogenase (E3)
d) contains between 1 and 3 copies of two regulatory enzymes, a kinase and a
phosphatase.
e) requires five cofactors
i) thiamine pyrophosphate
ii) lipoic acid
iii) flavin adenine dinucleotide
iv) Coenzyme A
v) NAD+.
f) Benefits of multi enzyme complex
i) improvement in catalytic efficiency
ii) coordinated catalysis
iii) increased overall reaction rate
iv) minimum of side reactions.
2) Cytoplasmic Pyruvate Must Enter the Mitochondria
a) Glycolytic pathway only partial use of glucose molecule
b) Complete oxidation of pyruvate to C02 and H20 occurs during Citric Acid Cycle
in mitochondria
i) Symport Mechanism
(1) pyruvate translocase transports the pyruvate molecule through the inner
mitochondrial membran
(2) OH or H+ exits
ii) pyruvate dehydrogenase complex converts pyruvate to acetyl-SCoA
(1) highly exergonic rxn
(2) irreversible
