The Citric Acid Cycle

• cellular respiration


  the process by which chemical energy is released through the oxidation of organic molecules
• metabolons


  transient, multi-protein complexes of sequential enzymes that mediate substrate channeling
• oncometabolites


  metabolites that occur in higher quantity in tumors compared to normal cells
• PDH kinase (PDK)


  enzyme which acts to inactivate enzyme pyruvate dehydrogenase by phosphorylating it using ATP
• PDH phosphatase


  catalyze the dephosphorylation and activation of the E1 component to reverse the effects of pyruvate dehydrogenase kinases
• mitochondrial pyruvate carrier (MPC)


  the sole entry point of entry for pyruvate into the mitochondrial matrix. Plays a key role in coordinating glycolytic and mitochondrial activities.
• Pyruvate carboxylase


  biotin-containing enzyme that catalyzes the HCO3- and MgATP-dependent carboxylation of pyruvate to form oxaloacetate.
• Amphibolic pathway


  biochemical pathway that includes both anabolic and catabolic processes
• Glyoxylate cycle


  special variant of the TCA cycle found only in plants, bacteria, fungi, and protists. Anabolic instead of catabolic like in humans
• The three major stages of cellular respiration are: glycolysis, citric acid cycle, and electron transport chain.
• First step of pyruvate oxidation

  a carboxyl group is removed from pyruvate, releasing carbon dioxide.
• Second step of pyruvate oxidation

  the electrons released from the oxidation of pyruvate are accepted by NAD+ to form NADH
• Third step of pyruvate oxidation

  an acetyl group (the oxidized two-carbon molecule) is transferred to coenzyme A, resulting in acetyl CoA.
• oxidation of pyruvate

  
• PDH complex is comprised of 3 principal enzymes and 5 different coenzymes
• The three principal enzymes of the PDH complex are E1, E2, and E3
• E1


  pyruvate dehydrogenase or pyruvate decarboxylase
• E2


  dihydrolipoyl transacetylase
• E3


  dihydrolipoyl dehydrogenase
• PDH coenzymes


  TPP, LIP, CoASH, FAD, NAD+
• TPP


  thiamine pyrophosphate
• LIP


  lipoic acid
• CoASH


  Coenzyme A
• FAD


  flavin adenine dinucleotide
• NAD+ 


  nicotinamide adenine dinucleotide
• Conversion of pyruvate to acetyl-CoA requires four vitamins: thiamine, pantothenic acid, riboflavin, and niacin
• The citric acid cycle does 2 turns per 1 glucose molecule
• Products of citric acid cycle (1 turn): 1 ATP/GTP, 1 FADH2, 3 NADH, 2CO2
• 1 glucose = 2 pyruvate = 2 Acetyl-CoA
• The citric acid cycle does not occur under anaerobic conditions
• In aerobic conditions, pyruvate enters the citric acid cycle and undergoes oxidative phosphorylation leading to the net production of 32 ATP molecules
• In anaerobic conditions, pyruvate converts to lactate through anaerobic glycolysis
• Anaerobic respiration results in the production of 2 ATP molecules
• The intermediates of the citric acid cycle are: citrate, isocitrate, alpha-ketoglutarate, succinate, fumarate, malate, oxaloacetate
• Anaplerotic reactions replenish the TCA cycle intermediates when they leak away from the cycle.
• anaplerosis


  the synthesis of intermediates needed for critical biological reactions
• The first step of the citric acid cycle is a condensation step, combining the two-carbon acetyl group (from acetyl CoA) with a four-carbon oxaloacetate molecule to form a six-carbon molecule of citrate
• The conversion of acetyl CoA and oxaloacetate is irreversible because it is highly exergonic
• Step one of the citric acid cycle is controlled by negative feedback and amount of ATP available. ATP increase, rate of reaction decreases and vice versa
• The step producing citrate is catalyzed by citrate synthase