Citric acid cycle

Krebs cycleTCA cycletricarboxylic acid cycletricarboxylic acid (TCA) cyclecitrate cycleTCAglycolysisKrebs citric acid cycletricarboxylic acidtricarboxylic acid cycle (TCA)
The citric acid cycle (CAC) – also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle – is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins, into adenosine triphosphate (ATP) and carbon dioxide.wikipedia
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Metabolism

metabolicmetabolizedmetabolic pathways
Its central importance to many biochemical pathways suggests that it was one of the earliest established components of cellular metabolism and may have originated abiogenically.
For example, the set of carboxylic acids that are best known as the intermediates in the citric acid cycle are present in all known organisms, being found in species as diverse as the unicellular bacterium Escherichia coli and huge multicellular organisms like elephants.

Albert Szent-Györgyi

Szent-GyörgyiAlbert Szent-GyorgyiAlbert von Szent-Györgyi Nagyrapolt
Several of the components and reactions of the citric acid cycle were established in the 1930s by the research of Albert Szent-Györgyi, who received the Nobel Prize in Physiology or Medicine in 1937 specifically for his discoveries pertaining to fumaric acid, a key component of the cycle.
He is credited with first isolating vitamin C and discovering the components and reactions of the citric acid cycle.

Adenosine triphosphate

ATPadenosine triphosphate (ATP)adenosine 5'-triphosphate
The citric acid cycle (CAC) – also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle – is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins, into adenosine triphosphate (ATP) and carbon dioxide.
ATP can be produced by a number of distinct cellular processes; the three main pathways in eukaryotes are (1) glycolysis, (2) the citric acid cycle/oxidative phosphorylation, and (3) beta-oxidation.

Hans Adolf Krebs

Hans KrebsSir Hans KrebsHans A. Krebs
The citric acid cycle itself was finally identified in 1937 by Hans Adolf Krebs and William Arthur Johnson while at the University of Sheffield, for which the former received the Nobel Prize for Physiology or Medicine in 1953, and for whom the cycle is sometimes named (Krebs cycle).
He is best known for his discoveries of two important sequences of chemical reactions that take place in the cells of humans and many other organisms, namely the citric acid cycle and the urea cycle.

Pyruvate dehydrogenase complex

pyruvate dehydrogenasemitochondrial pyruvate dehydrogenase complexPDC
One of the primary sources of acetyl-CoA is from the breakdown of sugars by glycolysis which yield pyruvate that in turn is decarboxylated by the pyruvate dehydrogenase complex generating acetyl-CoA according to the following reaction scheme:
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.

Succinate dehydrogenase

Complex IISDHsuccinate - coenzyme Q reductase
FADH 2 is covalently attached to succinate dehydrogenase, an enzyme which functions both in the CAC and the mitochondrial electron transport chain in oxidative phosphorylation. NADH, a product of all dehydrogenases in the citric acid cycle with the exception of succinate dehydrogenase, inhibits pyruvate dehydrogenase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and also citrate synthase.
It is the only enzyme that participates in both the citric acid cycle and the electron transport chain.

Oxidative phosphorylation

ATP generationmitochondrial oxidative phosphorylationoxidative
The NADH generated by the citric acid cycle is fed into the oxidative phosphorylation (electron transport) pathway.
Many catabolic biochemical processes, such as glycolysis, the citric acid cycle, and beta oxidation, produce the reduced coenzyme NADH.

Mitochondrial matrix

matrixmatrix of the mitochondriamitochondria
Several of the enzymes in the cycle may be loosely associated in a multienzyme protein complex within the mitochondrial matrix.
[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.

Flavin adenine dinucleotide

FADFADH 2 FADH2
FADH 2 is covalently attached to succinate dehydrogenase, an enzyme which functions both in the CAC and the mitochondrial electron transport chain in oxidative phosphorylation. The overall yield of energy-containing compounds from the TCA cycle is three NADH, one FADH 2, and one GTP.
Warburg’s work with linking nicotinamide to hydride transfers and the discovery of flavins paved the way for many scientists in the 40s and 50s to discover copious amounts of redox biochemistry and link them together in pathways such as the citric acid cycle and ATP synthesis.

Coenzyme A

CoAco-enzyme Acoenzyme-A
Here they can be oxidized and combined with coenzyme A to form CO 2, acetyl-CoA, and NADH, as in the normal cycle.
Coenzyme A (CoA, SCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle.

Citric acid

citratecitriccitrates
The name of this metabolic pathway is derived from the citric acid (a type of tricarboxylic acid, often called citrate, as the ionized form predominates at biological pH ) that is consumed and then regenerated by this sequence of reactions to complete the cycle.
In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the metabolism of all aerobic organisms.

Nucleoside-diphosphate kinase

nucleoside diphosphate kinaseNDKnucleoside diphosphate (NDP) kinase
The GTP that is formed by GDP-forming succinyl-CoA synthetase may be utilized by nucleoside-diphosphate kinase to form ATP (the catalyzed reaction is GTP + ADP → GDP + ATP).
NDPK activities maintain an equilibrium between the concentrations of different nucleoside triphosphates such as, for example, when guanosine triphosphate (GTP) produced in the citric acid (Krebs) cycle is converted to adenosine triphosphate (ATP).

Citrate synthase

citrate (Si)-synthaseCSCS (gene)
NADH, a product of all dehydrogenases in the citric acid cycle with the exception of succinate dehydrogenase, inhibits pyruvate dehydrogenase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and also citrate synthase.
The enzyme citrate synthase E.C. 2.3.3.1 (previously 4.1.3.7)] exists in nearly all living cells and stands as a pace-making enzyme in the first step of the citric acid cycle (or Krebs cycle).

Aconitase

iron regulatory protein 1iron regulatory protein 2aconitate hydratase
Aconitase (aconitate hydratase; ) is an enzyme that catalyses the stereo-specific isomerization of citrate to isocitrate via cis-aconitate in the tricarboxylic acid cycle, a non-redox-active process.

Tricarboxylic acid

tricarboxylatetricarboxylic
The name of this metabolic pathway is derived from the citric acid (a type of tricarboxylic acid, often called citrate, as the ionized form predominates at biological pH ) that is consumed and then regenerated by this sequence of reactions to complete the cycle.
Citric acid, a type of tricarboxylic acid, is used in the citric acid cycle – also known as tricarboxylic acid (TCA) cycle or Krebs cycle – which is fundamental to all aerobic organisms.

Guanosine triphosphate

GTPguanosine triphosphate (GTP)Guanosine-5'-triphosphate
The overall yield of energy-containing compounds from the TCA cycle is three NADH, one FADH 2, and one GTP.
For instance, a GTP molecule is generated by one of the enzymes in the citric acid cycle.

Oxalosuccinic acid

oxalosuccinateO'''xalosuccinate
Oxalosuccinic acid is a substrate of the citric acid cycle.

Succinic acid

succinatesuccinicsuccinyl
Succinate is generated in mitochondria via the tricarboxylic acid cycle (TCA).

Isocitrate dehydrogenase

EC 1.1.1.42IDHisocitrate dehydrogenase (NADP + )
NADH, a product of all dehydrogenases in the citric acid cycle with the exception of succinate dehydrogenase, inhibits pyruvate dehydrogenase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and also citrate synthase.
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.

Acetyl group

acetylAcacetylate
Acetyl-CoA is also created during the second stage of cellular respiration, the Krebs Cycle, by the action of pyruvate dehydrogenase on pyruvic acid.

Cofactor (biochemistry)

cofactorcofactorscoenzyme
For example, the multienzyme complex pyruvate dehydrogenase at the junction of glycolysis and the citric acid cycle requires five organic cofactors and one metal ion: loosely bound thiamine pyrophosphate (TPP), covalently bound lipoamide and flavin adenine dinucleotide (FAD), cosubstrates nicotinamide adenine dinucleotide (NAD + ) and coenzyme A (CoA), and a metal ion (Mg 2+ ).

Electron transport chain

respiratory chainelectron transportmitochondrial respiratory chain
FADH 2 is covalently attached to succinate dehydrogenase, an enzyme which functions both in the CAC and the mitochondrial electron transport chain in oxidative phosphorylation.
Most eukaryotic cells have mitochondria, which produce ATP from products of the citric acid cycle, fatty acid oxidation, and amino acid oxidation.

Aerobic organism

aerobicaerobic bacteriaaerobe
The citric acid cycle (CAC) – also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle – is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins, into adenosine triphosphate (ATP) and carbon dioxide.
This equation is a summary of what happens in three series of biochemical reactions: glycolysis, the Krebs cycle, and oxidative phosphorylation.

Abiogenesis

origin of lifeorigins of lifeformation
Its central importance to many biochemical pathways suggests that it was one of the earliest established components of cellular metabolism and may have originated abiogenically.
The centrality of the Krebs cycle (citric acid cycle) to energy production in aerobic organisms, and in drawing in carbon dioxide and hydrogen ions in biosynthesis of complex organic chemicals, suggests that it was one of the first parts of the metabolism to evolve.

Alpha-Ketoglutaric acid

2-oxoglutarateα-ketoglutaratealpha-ketoglutarate
In this reaction the glutamate is converted into alpha-ketoglutarate, which is a citric acid cycle intermediate.
It is the keto acid produced by deamination of glutamate, and is an intermediate in the Krebs cycle.