Tricarboxylic Acid Cycle Flashcards

A set of vocabulary-style flashcards covering the enzymes, coenzymes, regulation, and biochemical steps of the Tricarboxylic Acid Cycle and the Pyruvate Dehydrogenase Complex.

Tricarboxylic Acid Cycle (TCA Cycle)

Also known as the Krebs or citric acid cycle, it is the final catabolic pathway taking place in the mitochondrial matrix where fuel is completely oxidized to $CO_2$ and $H_2O$.

Pyruvate Dehydrogenase Complex (PDH)

A huge multienzyme complex in the mitochondrial matrix that catalyzes the irreversible conversion of Pyruvate + $CoA$ + $NAD^+$ into $acetyl-CoA$ + $CO_2$ + $NADH$ + $H^+$.

$E_1$ (Pyruvate dehydrogenase)

The first enzyme of the PDH complex which requires the coenzyme Thiamine pyrophosphate (TPP).

$E_2$ (Dihydrolipoyl transacetylase)

The second enzyme of the PDH complex which requires the coenzymes Lipoamide and Coenzyme A (CoASH).

$E_3$ (Dihydrolipoyl dehydrogenase)

The third enzyme of the PDH complex which requires the coenzymes Flavin adenine dinucleotide (FAD) and Nicotinamide adenine dinucleotide ($NAD^+$).

Beriberi

A condition caused by a lack of thiamine ($B_1$) or impairment of its utilization, often seen with excessive alcohol consumption which inhibits thiamine absorption.

Pyruvate Dehydrogenase Kinase

An enzyme that inhibits $E_1$ by phosphorylation; it is activated by high levels of $ATP$, $NADH$, and $acetyl-CoA$, and inhibited by $ADP$ and pyruvate.

Pyruvate Dehydrogenase Phosphatase

An enzyme that activates the PDH complex by dephosphorylating $E_1$; it is stimulated by $Ca^{2+}$ and insulin.

Citrate Synthase

The enzyme that catalyzes Step 1 of the TCA cycle, forming citrate from oxaloacetate and $acetyl-CoA$; it is negatively regulated by $NADH$ and $succinyl-CoA$.

Aconitase

The enzyme responsible for the isomerization of citrate to isocitrate via the intermediate $cis-aconitate$.

Isocitrate Dehydrogenase

The enzyme for the first dehydrogenation and spontaneous decarboxylation in the TCA cycle; it is positively modulated by $ADP$ and negatively by $ATP$ and $NADH$.

$\alpha-Ketoglutarate$ Dehydrogenase Complex

A multienzyme complex mechanically identical to PDH that catalyzes the second decarboxylation and dehydrogenation, resulting in the loss of the third carbon from the original pyruvate.

Succinyl-CoA Synthetase

The enzyme that catalyzes the release of energy from the thioester bond of $succinyl-CoA$ to phosphorylate $GDP$ to $GTP$.

Succinate Dehydrogenase

The TCA cycle enzyme that uses $FAD$ instead of $NAD^+$ as a hydrogen acceptor; the resulting $FADH_2$ is reoxidized by $O_2$ in the Electron Transport Chain.

Fumarase

The enzyme that incorporates $H_2O$ across the double bond of fumarate to form malate.

Malate Dehydrogenase

The final enzyme of the TCA cycle which converts malate to oxaloacetate using $NAD^+$ as the hydrogen acceptor.

Glutaminolysis

The process where glutamine is converted to glutamate by glutaminase and subsequently transformed into $\alpha-ketoglutarate$ to enter the TCA cycle.

Lipoic Acid (lipoamide)

A coenzyme of the $E_2$ subunit that acts as an acetyl group carrier and is regenerated in the final steps of the PDH complex mechanism.

$GTP$ (Guanosine Triphosphate)

A high-energy molecule produced in Step 5 of the TCA cycle that can transfer its phosphate to $ADP$ to make $ATP$ or serve as a donor in gluconeogenesis.

Thermodynamics of PDH Reaction

The conversion of pyruvate to $acetyl-CoA$ is an irreversible reaction with a $\Delta G^{\circ'} = -33.5\,kJ/mol$.

What amino acids can get converted to pyruvate

Alanine, glycine, serine, threonine, cysteine, tryptophan

What amino acids can get converted to alpha-keto-glutarate

Glutamate, glutamine, histadine, arginine, proline