The citric acid cycle (CAC)—also known as the Krebs cycle, Szent-Györgyi-Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. The Krebs cycle is used by organisms that respire (as opposed to organisms that ferment) to generate energy, either by anaerobic respiration or aerobic respiration. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism. Even though it is branded as a 'cycle', it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized.
Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and this complex links the glycolysis metabolic pathway to the citric acid cycle. Pyruvate decarboxylation is also known as the "pyruvate dehydrogenase reaction" because it also involves the oxidation of pyruvate.
Glutamate dehydrogenase is an enzyme observed in both prokaryotes and eukaryotic mitochondria. The aforementioned reaction also yields ammonia, which in eukaryotes is canonically processed as a substrate in the urea cycle. Typically, the α-ketoglutarate to glutamate reaction does not occur in mammals, as glutamate dehydrogenase equilibrium favours the production of ammonia and α-ketoglutarate. Glutamate dehydrogenase also has a very low affinity for ammonia, and therefore toxic levels of ammonia would have to be present in the body for the reverse reaction to proceed. However, in brain, the NAD+/NADH ratio in brain mitochondria encourages oxidative deamination. In bacteria, the ammonia is assimilated to amino acids via glutamate and aminotransferases. In plants, the enzyme can work in either direction depending on environment and stress. Transgenic plants expressing microbial GLDHs are improved in tolerance to herbicide, water deficit, and pathogen infections. They are more nutritionally valuable.
Malate dehydrogenase (EC 1.1.1.37) (MDH) is an enzyme that reversibly catalyzes the oxidation of malate to oxaloacetate using the reduction of NAD+ to NADH. This reaction is part of many metabolic pathways, including the citric acid cycle. Other malate dehydrogenases, which have other EC numbers and catalyze other reactions oxidizing malate, have qualified names like malate dehydrogenase (NADP+).
Isocitrate dehydrogenase (IDH) (EC 1.1.1.42) and (EC 1.1.1.41) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2. This is a two-step process, which involves oxidation of isocitrate (a secondary alcohol) to oxalosuccinate (a ketone), followed by the decarboxylation of the carboxyl group beta to the ketone, forming alpha-ketoglutarate. In humans, IDH exists in three isoforms: IDH3 catalyzes the third step of the citric acid cycle while converting NAD+ to NADH in the mitochondria. The isoforms IDH1 and IDH2 catalyze the same reaction outside the context of the citric acid cycle and use NADP+ as a cofactor instead of NAD+. They localize to the cytosol as well as the mitochondrion and peroxisome.
In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.
The oxoglutarate dehydrogenase complex (OGDC) or α-ketoglutarate dehydrogenase complex is an enzyme complex, most commonly known for its role in the citric acid cycle.
Pyruvate carboxylase (PC) encoded by the gene PC is an enzyme of the ligase class that catalyzes the physiologically irreversible carboxylation of pyruvate to form oxaloacetate (OAA).
GLUD1 is a mitochondrial matrix enzyme, one of the family of glutamate dehydrogenases that are ubiquitous in life, with a key role in nitrogen and glutamate (Glu) metabolism and energy homeostasis. This dehydrogenase is expressed at high levels in liver, brain, pancreas and kidney, but not in muscle. In the pancreatic cells, GLUD1 is thought to be involved in insulin secretion mechanisms. In nervous tissue, where glutamate is present in concentrations higher than in the other tissues, GLUD1 appears to function in both the synthesis and the catabolism of glutamate and perhaps in ammonia detoxification.
The branched-chain α-ketoacid dehydrogenase complex is a multi-subunit complex of enzymes that is found on the mitochondrial inner membrane. This enzyme complex catalyzes the oxidative decarboxylation of branched, short-chain alpha-ketoacids. BCKDC is a member of the mitochondrial α-ketoacid dehydrogenase complex family comprising pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, key enzymes that function in the Krebs cycle.
The malate-aspartate shuttle is a biochemical system for translocating electrons produced during glycolysis across the semipermeable inner membrane of the mitochondrion for oxidative phosphorylation in eukaryotes. These electrons enter the electron transport chain of the mitochondria via reduction equivalents to generate ATP. The shuttle system is required because the mitochondrial inner membrane is impermeable to NADH, the primary reducing equivalent of the electron transport chain. To circumvent this, malate carries the reducing equivalents across the membrane.
Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids).
The mitochondrial shuttles are biochemical transport systems used to transport reducing agents across the inner mitochondrial membrane. NADH as well as NAD+ cannot cross the membrane, but it can reduce another molecule like FAD and [QH2] that can cross the membrane, so that its electrons can reach the electron transport chain.
Aspartate aminotransferase, mitochondrial is an enzyme that in humans is encoded by the GOT2 gene. Glutamic-oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and inner-membrane mitochondrial forms, GOT1 and GOT2, respectively. GOT plays a role in amino acid metabolism and the urea and Kreb's cycle. Also, GOT2 is a major participant in the malate-aspartate shuttle, which is a passage from the cytosol to the mitochondria. The two enzymes are homodimeric and show close homology. GOT2 has been seen to have a role in cell proliferation, especially in terms of tumor growth.
Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial (IDH3α) is an enzyme that in humans is encoded by the IDH3A gene.
Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial is an enzyme that in humans is encoded by the IDH3G gene.
Glutaminolysis (glutamine + -lysis) is a series of biochemical reactions by which the amino acid glutamine is lysed to glutamate, aspartate, CO2, pyruvate, lactate, alanine and citrate.
Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial is an enzyme that in humans is encoded by the IDH3B gene.
Malate dehydrogenase, cytoplasmic also known as malate dehydrogenase 1 is an enzyme that in humans is encoded by the MDH1 gene.
The citrate-malate shuttle is a series of chemical reactions – commonly referred to as a biochemical cycle or system – that transports acetyl-CoA in the mitochondrial matrix across the inner and outer mitochondrial membrane for fatty acid synthesis. Mitochondria, also known as the powerhouse of a cell, is enclosed in a double membrane. As the inner mitochondrial membrane is impermeable to acetyl-CoA, the shuttle system is essential to fatty acid synthesis in the cytosol. It plays an important role in the generation of lipids in the liver.
