Krebs Cycle and PDC Insights

A series of biochemical reactions that occur in the mitochondria of cells. It is the central pathway for the oxidation of carbohydrates, fats, and proteins to produce energy in the form of ATP.

The Krebs cycle is localized in the mitochondria, specifically in the mitochondrial matrix.

The pyruvate dehydrogenase complex (PDC) is a multi-enzyme complex responsible for converting pyruvate, the end product of glycolysis, into acetyl-CoA. This conversion is crucial for the entry of pyruvate into the Krebs cycle.

Malonate is an inhibitor of the enzyme succinate dehydrogenase, which is involved in the Krebs cycle. Malonate's inhibitory effect on succinate dehydrogenase prevents the oxidation of succinate to fumarate, disrupting the cycle and reducing ATP production.

The Krebs cycle is a key pathway in cellular respiration. It's responsible for the oxidation of pyruvate, leading to the production of electron carriers (NADH and FADH2) that fuel the electron transport chain for ATP synthesis.

The regulation of the Krebs cycle ensures that its rate matches the cell's energy demands. Factors like the availability of substrates (like pyruvate and O2), the levels of ATP and ADP, and the activity of key enzymes, all contribute to controlling the cycle's activity.

The Krebs cycle is named after Sir Hans Adolf Krebs, a British biochemist who elucidated its intricate mechanism in the 1930s, earning him the Nobel Prize in Physiology or Medicine in 1953.

Szent-Gyorgyi, a Hungarian biochemist, was a pioneer in studying the Krebs cycle. He demonstrated how certain molecules, like succinate, fumarate, malate, and oxaloacetate, could speed up the rate of respiration.

A multi-enzyme complex that catalyzes the conversion of pyruvate to acetyl-CoA. It is composed of three enzymes: pyruvate dehydrogenase (E1), dihydrolipoyl transacetylase (E2), and dihydrolipoyl dehydrogenase (E3).

The first enzyme in the PDC complex, responsible for decarboxylating pyruvate and releasing carbon dioxide. It requires thiamine pyrophosphate (TPP) as a cofactor.

The second enzyme in the PDC complex, responsible for transferring the acetyl group from a lipoyl group to Coenzyme A (CoA), forming acetyl-CoA. It contains lipoic acid bound to its active site.

The third enzyme in the PDC complex, responsible for oxidizing the reduced lipoyl group, regenerating the lipoyl group and reducing NAD+ to NADH. It contains FAD bound to its active site.

A deficiency in thiamine (Vitamin B1) can lead to Beriberi.

A fatal disease caused by thiamine deficiency, characterized by neurological disturbances, paralysis, atrophy of limbs, and cardiac failure.

Thiamine pyrophosphate is the active form of thiamine essential for the PDC to function properly.

Essential for energy production in the brain, using glucose exclusively for aerobic metabolism.

The first step in the TCA cycle, where Acetyl CoA combines with Oxaloacetate to form Citrate. This reaction is catalyzed by Citrate Synthase. It involves an induced fit model where the enzyme's conformation changes upon binding to substrates, facilitating the reaction.

Aconitase catalyzes the isomerization of Citrate to Isocitrate by removing and adding water at different positions, forming cis-Aconitate as an intermediate. The rapid consumption of Isocitrate by the next step pulls the reaction forward (Le Chatelier's Principle).

Isocitrate Dehydrogenase is an enzyme that catalyzes the oxidative decarboxylation of Isocitrate into alpha-ketoglutarate, producing NADH or NADPH (depending on the isoform). This reaction is an important source of reducing equivalents (electron carriers) in the cell.

Alpha-ketoglutarate Dehydrogenase is a multi-enzyme complex that catalyzes the oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA, generating NADH and CO2. This is another important step in the TCA cycle.

Succinyl-CoA Synthetase is an enzyme that catalyzes the conversion of succinyl-CoA into succinate, generating GTP (an important energy carrier) in the process. This is a crucial step in the TCA cycle.

Succinate Dehydrogenase is an enzyme embedded in the inner mitochondrial membrane, which catalyzes the oxidation of succinate to fumarate, directly transferring electrons to the electron transport chain.

Fumerase is an enzyme that catalyzes the hydration of fumarate to L-malate, which is a reversible reaction.

Malate Dehydrogenase is an enzyme that catalyzes the oxidation of L-malate to oxaloacetate, generating NADH in the process. This important step completes the TCA cycle, regenerating oxaloacetate that can then enter another round of the cycle for further ATP production.

A multi-enzyme complex that oxidizes α-ketoglutarate to succinyl CoA, similar to the pyruvate dehydrogenase complex. It requires NAD+ as an electron acceptor and involves E1, E2, and E3 enzyme units.

An enzyme that catalyzes the conversion of succinyl CoA to succinate. It uses the energy from the thioester bond to produce GTP, a high-energy phosphate molecule.

An enzyme that oxidizes succinate to fumarate. It's the only enzyme in the citric acid cycle that is tightly bound to the inner mitochondrial membrane. It uses FAD as an electron acceptor.

An enzyme that adds water to the double bond of fumarate, converting it to malate. It is highly specific for the cis isomer of fumarate.

An enzyme that oxidizes malate to oxaloacetate. It uses NAD+ as an electron acceptor. The reaction is pulled forward by the next step in the cycle, which rapidly consumes oxaloacetate.

The main regulatory points in the citric acid cycle, these enzymes control the rate of the cycle.

The citric acid cycle is regulated by the availability of substrates, the accumulation of products, and the allosteric effects of other cycle intermediates.

The intermediates of the citric acid cycle are used in several other metabolic pathways, including glucose biosynthesis, lipid biosynthesis, amino acid biosynthesis, and porphyrin biosynthesis.