The tricarboxylic acid (TCA) cycle is a metabolic pathway that converts acetyl-CoA into carbon dioxide, generating reduced cofactors NADH and FADH2 which feed into the electron transport chain. Key enzymes in the TCA cycle include citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate thiokinase, succinate dehydrogenase, and malate dehydrogenase. Many of these enzymes require vitamins B1, B2, B3, B5 as cofactors.
The tricarboxylic acid (TCA) cycle is a metabolic pathway that converts acetyl-CoA into carbon dioxide, generating reduced cofactors NADH and FADH2 which feed into the electron transport chain. Key enzymes in the TCA cycle include citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate thiokinase, succinate dehydrogenase, and malate dehydrogenase. Many of these enzymes require vitamins B1, B2, B3, B5 as cofactors.
The tricarboxylic acid (TCA) cycle is a metabolic pathway that converts acetyl-CoA into carbon dioxide, generating reduced cofactors NADH and FADH2 which feed into the electron transport chain. Key enzymes in the TCA cycle include citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate thiokinase, succinate dehydrogenase, and malate dehydrogenase. Many of these enzymes require vitamins B1, B2, B3, B5 as cofactors.
The tricarboxylic acid (TCA) cycle is a metabolic pathway that converts acetyl-CoA into carbon dioxide, generating reduced cofactors NADH and FADH2 which feed into the electron transport chain. Key enzymes in the TCA cycle include citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate thiokinase, succinate dehydrogenase, and malate dehydrogenase. Many of these enzymes require vitamins B1, B2, B3, B5 as cofactors.
I. Tricarboxylic acid (TCA) cycle overview c) Activates acetyl-CoA carboxylase and
increases fatty acid synthesis A. A metabolic pathway that converts acetyl-CoA → CO2 2. Inhibited by ATP
B. Generates NADH and FADH2 → electron B. Isocitrate dehydrogenase
transport chain → cellular energy 1. Isocitrate → α-ketoglutarate dehydrogenase 1. Also generates guanosine triphosphate 2. Produces NADH and CO2 (GTP) 3. Inhibited by ATP and NADH and activated by C. Occurs within the mitochondria. ADP 4. Requires niacin as a cofactor and for the production of NAD+ II. Important enzymes C. α-ketoglutarate dehydrogenase A. Citrate synthase 1. α-ketoglutarate → Succinyl-CoA 1. Oxaloacetate → citrate 2. Produces NADH and CO2 a) Citrate is a marker of sufficient energy 3. Inhibited by ATP, NADH, and Succinyl-CoA b) Blocks phosphofructokinase-1 and 4. Activated by Ca2+ in skeletal muscle tissue decreases glycolysis
Figure 2.5.5 - TCA Cycle
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5. Similar complex to pyruvate
dehydrogenase REVIEW QUESTIONS ? 1. A 47-year-old homeless male is brought to the a) Requires 5 cofactors including ED after being found unconscious on the side thiamine (vitamin B1), lipoic acid, of the road. He is resuscitated and complains of CoA (vitamin B5), FAD (vitamin B2), difficulty walking and remembering past events. and NAD (vitamin B3). On exam he is ataxic and has ophthalmoplegia. b) Mnemonic: “TLC for Nancy.” What enzyme in the TCA cycle is likely altered as D. Succinate thiokinase a result of this patient’s condition? 1. Succinyl-CoA → succinate • Memory loss, ataxia, and ophthalmoplegia 2. Produces GTP are consistent with Wernicke-Korsakoff syn- drome (caused by thiamine deficiency) E. Succinate dehydrogenase • α-ketoglutarate is the only enzyme in the 1. Succinate → fumarate TCA cycle that requires thiamine as a cofac- tor 2. Complex II of the ETC 3. FAD is a constituent of riboflavin 2. A 24-year-old woman with a history of anorexia (vitamin B2) so this reaction is vitamin nervosa presents with fissures at the corners B2-dependent. of her mouth and severe inflammation of her lips. On exam she has corneal clouding due to F. Malate dehydrogenase vascularization. What two reactions in the TCA 1. Malate → oxaloacetate cycle will likely be altered as a result of this 2. Niacin (Vitamin B3) is necessary for patient’s condition? the production of NAD+ and acts as a • Inflammation at the lips and fissures at the cofactor for this enzyme. corners of her mouth → cheilosis • Cheilosis and corneal vascularization are seen in vitamin B2 deficiency • ↓ vitamin B2 → ↓ α-ketoglutarate dehydro- genase (α-ketoglutarate → succinyl-CoA) • ↓ vitamin B2 → ↓ succinate dehydrogenase (succinate → fumarate)