Medical Biochemistry: Citric Acid Cycle (TCA Cycle)

Flashcards covering the reactions, enzymes, energy production, electron carriers, and stoichiometry of the Tricarboxylic Acid (TCA) Cycle.

What are the alternative names for the Tricarboxylic Acid (TCA) Cycle, and in which cellular organelle does it take place?

The TCA cycle is also known as the Citric Acid Cycle or Krebs Cycle, and it takes place in the mitochondria.

What is the central metabolic role of the TCA cycle regarding nutrient oxidation?

It serves as a central metabolic pathway that oxidizes acetyl-CoA derived from carbohydrates, fats, and amino acids, generating energy and supplying intermediates for biosynthesis.

Which three high-energy molecules are generated by the TCA cycle under aerobic conditions?

The cycle produces $ATP$ (adenosine triphosphate), $NADH$ (nicotinamide adenine dinucleotide), and $FADH_2$ (flavin adenine dinucleotide).

What is the primary function of $ATP$ in cellular metabolism, and how is its energy released?

$ATP$ is the universal energy currency of the cell that powers essential processes such as muscle contraction, active transport, and biosynthesis; it releases energy by breaking high-energy phosphate bonds.

What roles does $NADH$ fulfill during cellular respiration?

$NADH$ functions as a vital electron carrier that accepts high-energy electrons and protons during metabolic reactions and contributes to the generation of $ATP$ in the electron transport chain.

What is the role of $FADH_2$ in energy metabolism?

$FADH_2$ is an electron carrier that transfers high-energy electrons to the electron transport chain during cellular respiration, supporting the production of $ATP$ and the establishment of a proton gradient.

Based on the provided overview of mitochondrial respiration, what three fuel sources feed into Acetyl CoA, and what are the direct outputs of the Citric Acid Cycle?

Fatty acids, glucose, and amino acids provide Acetyl CoA. The cycle directly yields $1\text{ GTP}$, $2\text{ CO}_2$, and $8\text{ e}^-$ (which feed into the electron-transport chain to establish a proton gradient of $\sim 36\text{ H}^+$).

What reaction is catalyzed by the pyruvate dehydrogenase (PDH) complex prior to entry into the TCA cycle?

Pyruvate undergoes oxidative decarboxylation according to the reaction: $\text{Pyruvate} + \text{CoA} + \text{NAD}^+ \rightarrow \text{Acetyl-CoA} + \text{CO}_2 + \text{NADH} + \text{H}^+$.

What occurs in Step 1 of the TCA cycle, and which enzyme catalyzes it?

Citrate synthase catalyzes a condensation reaction in which acetyl-CoA combines with oxaloacetate to form citrate.

Which enzyme catalyzes Step 2 of the TCA cycle, and what structural change takes place?

Aconitase catalyzes the isomerization of the $\text{-OH}$ group on citrate to form isocitrate.

What reaction occurs in Step 3 of the TCA cycle, and which enzyme catalyzes it?

Isocitrate dehydrogenase catalyzes the first oxidative decarboxylation step, converting isocitrate to $\alpha\text{-ketoglutarate}$ with the release of $\text{CO}_2$ and generation of $\text{NADH}$.

What reaction occurs in Step 4 of the TCA cycle, and which enzyme complex is responsible?

The $\alpha\text{-ketoglutarate}$ dehydrogenase complex catalyzes the second oxidative decarboxylation step, converting $\alpha\text{-ketoglutarate}$ into succinyl-CoA while releasing $\text{CO}_2$ and producing $\text{NADH}$.

What enzyme catalyzes Step 5 of the TCA cycle, and how is energy captured during this reaction?

Succinyl-CoA synthetase hydrolyzes the high-energy thioester bond in succinyl-CoA to form succinate, driving substrate-level phosphorylation to yield $GTP$ or $ATP$.

What reaction occurs in Step 6 of the TCA cycle, and what is unique about the enzyme involved?

Succinate dehydrogenase dehydrogenates succinate to produce fumarate while generating $FADH_2$. This enzyme also functions directly as Complex II in the electron transport chain.

Which enzyme catalyzes Step 7 of the TCA cycle, and what type of reaction occurs?

Fumarase (fumarate hydratase) catalyzes a hydration reaction, adding water ($\text{H}_2\text{O}$) across fumarate to form malate.

What occurs in Step 8 of the TCA cycle to regenerate the starting metabolite?

Malate dehydrogenase oxidizes malate to regenerate oxaloacetate, producing a molecule of $\text{NADH}$.

Which specific steps of the TCA cycle are oxidative decarboxylation reactions that release carbon dioxide ($\text{CO}_2$)?

Step 3 (conversion of isocitrate to $\alpha\text{-ketoglutarate}$ by isocitrate dehydrogenase) and Step 4 (conversion of $\alpha\text{-ketoglutarate}$ to succinyl-CoA by $\alpha\text{-ketoglutarate}$ dehydrogenase complex).

Which step in the TCA cycle directly performs substrate-level phosphorylation?

Step 5, in which succinyl-CoA synthetase couples the conversion of succinyl-CoA to succinate with the synthesis of $GTP$ (or $ATP$) from $GDP$ (or $ADP$) and $P_i$.