Pyruvate Dehydrogenase (PDH) Complex

This set of vocabulary flashcards covers the structure, enzymatic components, coenzymes, regulatory mechanisms, and clinical pathologies associated with the Pyruvate Dehydrogenase (PDH) Complex.

Pyruvate mitochondrial carrier

A transport protein located in the inner mitochondrial membrane that moves pyruvate from the cytosol into the mitochondrial matrix.

Pyruvate decarboxylase ([E1])

A component enzyme of the PDHC that decarboxylates pyruvate to form a hydroxyethyl derivative bound to thiamine pyrophosphate.

Dihydrolipoyl transacetylase (E2)

A component enzyme of the PDHC that transfers an acetyl group, bound as a thioester to lipoic acid, to Coenzyme A (CoA).

Dihydrolipoyl dehydrogenase (E3)

A component enzyme of the PDHC that reoxidizes the sulfhydryl form of lipoic acid to its disulfide form using $FAD$ and $NAD^+$.

Pyruvate dehydrogenase kinase (PDH kinase)

A regulatory enzyme that phosphorylates and inactivates the E1 component of the PDH complex.

Pyruvate dehydrogenase phosphatase (PDH phosphatase)

A regulatory enzyme that dephosphorylates and activates the E1 component of the PDH complex.

Thiamine pyrophosphate (TPP)

The coenzyme for the E1 component (Pyruvate decarboxylase), derived from Vitamin B1.

Lipoic acid

A coenzyme for the E2 component that is covalently bound to dihydrolipoyl transacetylase and oscillates between oxidized (disulfide) and reduced (sulfhydryl) forms.

Coenzyme A (CoA)

A coenzyme for the E2 component, also known as Vitamin B5, which accepts an acetyl group to become acetyl CoA.

FAD and NAD+

The coenzymes for the E3 component, derived from Vitamin B2 and Vitamin B3 respectively, used to transfer electrons for the regeneration of lipoic acid.

PDH Kinase Activators

$ATP$, $NADH$, and Acetyl CoA.

PDH Kinase Inhibitors

Pyruvate, $NAD^+$, and CoA.

PDH Phosphatase Activators

$Ca^{2+}$, $Mg^{2+}$, and Insulin (specifically in adipose tissue).

Congenital Lactic acidosis

An X-linked dominant genetic disorder caused by a deficiency in the $\alpha$ subunits of the E1 component, resulting in the shunting of pyruvate to lactate.

Leigh syndrome

A rare, progressive, neurodegenerative disorder (subacute necrotizing encephalomyelopathy) caused by mutations in genes encoding PDHC, the ETC, or ATP synthase.

Wernicke–Korsakoff

An encephalopathy-psychosis syndrome due to thiamine deficiency, often seen in alcohol use disorder, characterized by ataxia, confusion, and memory loss.

Beriberi

A thiamine deficiency disease that can be 'dry' (polyneuropathy and muscle wasting) or 'wet' (edema and high-output cardiac failure).

Arsenate

The pentavalent form of arsenic that interferes with glycolysis at the glyceraldehyde 3-phosphate step.

Arsenite

The trivalent form of arsenic that forms a stable complex with the thiol ($-SH$) groups of lipoic acid, inactivating enzymes like PDH and $\alpha$-ketoglutarate dehydrogenase.