BIOC 460 - DR. TISCHLER

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BIOC 460 - DR. TISCHLER LECTURE 27
PYRUVATE DEHYDROGENASE/ CITRIC ACID CYCLE
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OBJECTIVES

• Pathways in mitochondrial matrix role of inner
  membrane cristae
• PDH reaction
• a) reactants products for E1, E2, E3
  components
• cofactors associated with each prosthetic group
  or a co-substrate vitamin source function
• nutritional deficiencies severely impair
• regulation of the PDH complex (allostery
  covalent modification)
• 3. Reactions of citric acid cycle where NADH,
  FADH2, GTP form
• 4. Compounds that regulate the citric acid
  cycle, enzymes they
• regulate, their effect

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Figure 1. The Mitochondrion
Impermeable to all charged molecules and neutral
gt 100 MW
PDH citric acid cycle fatty acid ?-oxidation
ketone metabolism gluconeogenesis urea cycle
(part)
Increase surface area contains electron
transport membrane transporters
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CoASH
CoASH
Pyruvate
E3
E1

E2

NAD

Lipoate

TPP thiamine pyrophosphate

S
S

substrates

products

prosthetic group

coenzymes

Figure 2. The pyruvate dehydrogenase complex
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E3
E1

E2

NAD

TPP thiamine pyrophosphate

substrates

products

prosthetic group

coenzymes

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E3
E1

E2

NADH
NAD
TPP thiamine pyrophosphate

substrates

products

prosthetic group

coenzymes

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Table 1. Cofactors for each component of the PDH
complex with the cofactor category and vitamin
source
Subunit Cofactor Type Vitamin Source
E1 Thiamine pyrophosphate Prosthetic Thiamine
E2 Coenzyme A Lipoamide (lipoic acid lys residue) Co-substrate Prosthetic Pantothenic acid none-dietary
E3 FAD NAD Prosthetic Co-substrate Riboflavin Niacin
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Figure 3. Allosteric feedback inhibition of E2
by acetyl CoA and E3 by NADH
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Figure 4. Regulation of E1 by covalent
modification through phosphorylation
NAD
CoASH

ACTIVE ENZYME

Pyruvate
E3
E2
E1
NADH

Acetyl CoA
CO2
activate PDH kinase
PDH Kinase
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Glucose
Figure 5. Reactions of the citric acid cycle.


fatty acids, ketone bodies
glycolysis

PDH



Acetyl CoA
Pyruvate

Oxaloacetate

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Citrate Synthase oxaloacetate acetyl CoA
? citrate
CoA-SH
Isocitrate Dehydrogenase isocitrate NAD
? ?-ketoglutarate NADH CO2
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?-Ketoglutarate Dehydrogenase
?-Ketoglutarate CoA NAD ? Succinyl CoA
NADH CO2
Succinyl CoA Synthetase Succinyl CoA GDP
? Succinate GTP
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Succinate Dehydrogenase Succinate FAD ?
Fumarate FADH2
Malate Dehydrogenase Malate NAD ?
Oxaloacetate NADH
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Table 2. Allosteric regulation of the citric
acid cycle.
Enzyme regulated Regulatory substance Effect
Isocitrate dehydrogenase ADP NADH, ATP activation inhibition
?-Ketoglutarate dehydrogenase NADH, succinyl CoA, GTP inhibition