Pyruvate Dehydrogenase Complex

PDC substrate

pyruvate

PDC product

Acetyl CoA

PDC location

mitochondrial matrix

Cofactors

Thiamine, Lipoic Acid, CoA, FAD, and NAD

Cofactors in Enzyme Component 1

Thiamine

Cofactors in Enzyme Component 2

Lipoic acid and CoA (Vitamin B5)

Cofactors in E3

FAD (Vitamin B2) and NAD (Vitamin B3)

Enzyme Component 1

pyruvate dehydrogenase

E1 function

decarboxylate pyruvate

Enzyme component 2

Dihydrolipoyl transacetylase

E2 function

transfer acetyl group to CoA using lipoamine

Enzyme component 3

Dihydrolipoyl dehydrogenase

E3 function

uses FAD to regenerate oxidized lipoamine to produce NADH

PDC Inactivation conditions

high ATP, high NADH, high Acetyl CoA

PDC Inactivation

PDH kinase phosphorylates E1

PDC Activation conditions

high ADP, high NAD, high CoA

PDC Activation

PDH phosphatase dephosphorylates E1

Hormonal affects to PDC

insulin activates PDH phosphatase, Calcium in muscles activates PDC

Deficiency in PDC

pyruvate accumulation causing lactic acidosis

Management for basic PDC deficiency

ketogenic diet

Poisoning target of PDC

Arsenite

PDCD cause

genetic, mitochondrial disorder

PDCD main symptoms

abnormal eye movement and abnormal face shape

Diagnosis of PDCD

increased pyruvate AND lactic acid levels in blood and urine, brain MRI, enzyme assay, and genetic testing

PDCD cure

no known cure, symptom management