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The TCA cycle is part of the larger glucose metabolism whereby glucose is oxidized to
form pyruvate, which is then oxidized and enters the TCA cycle as acetyl-CoA.
Half of the intermediates on which the cycle depends are also the origin of pathways
leading to important compounds such as fatty acids, amino acids, or porphyrins. If any of
these intermediates are thus diverted, the integrity of the cycle is broken and the cycle
no longer functions. Production of essential energy can only be resumed if the diverted
intermediate or a subsequent intermediate that leads to oxaloacetate can be replenished
by anaplerotic (refilling) reactions.
1. Citrate
2. Isocitrate
3. Oxoglutarate
4. Succinyl-CoA
5. Succinate
6. Fumarate
7. Malate
8. Oxaloacetate (oxaloacetic acid)
KREBS CYCLE STEPS
1. The TCA cycle begins with an enzymatic aldol addition reaction of acetyl CoA to
oxaloacetate, forming citrate.
2. The citrate is isomerized by a dehydration-hydration sequence to yield (2R,3S)-
isocitrate.
3. Further enzymatic oxidation and decarboxylation gives 2-ketoglutarate.
4. After another enzymatic decarboxylation and oxidation, 2-ketoglutarate is
transformed into succinyl-CoA.
5. The hydrolysis of this metabolite to succinate is coupled to the phosphorylation
of guanosine diphosphate (GDP) to guanosine triphosphate (GTP).
6. Enzymatic desaturation by flavin adenine dinucleotide (FAD)-dependent succinate
dehydrogenase yields fumarate.
7. After stereospecific hydration, fumarate catalyzed by fumarase is transformed to
L-malate.
8. The last step of NAD-coupled oxidation of L-malate to oxaloacetate is catalyzed
by malate dehydrogenase and closes the cycle.
FROM?
The reducing power at this stage is largely conserved as NADH and ubiquinol (UQH 2) in
the mitochondrial inner membrane prior to a series of oxidation reactions that end in
water. These oxidations power the translocation of protons from the matrix to the
intermembrane space. This leads to a potential gradient (proton pump) that drives the
retro-location of protons to the matrix and thus activates ATP synthase, which catalyzes
ATP formation.
GTP
3 NADH
FADH2, which is converted to UQH2 in the presence of coenzyme Q (ubiquinone)
2 CO2 (carbon dioxide)
WHAT IS PYRUVATE?
Pyruvate is a biological molecule and product of glucose metabolism that reacts with
adenosine triphosphate and carbon dioxide, converting it into acetyl-CoA and adenosine
diphosphate (ADP) at the beginning of the TCA cycle. It is often included in the
introductory or preliminary step of the cycle.
Pyruvate usually derives from the glycolysis product pyruvic acid, which quickly
dissociates in most natural systems, leaving pyruvate.
Lipid Metabolism
Amino Acid Metabolism
Protein Metabolism (Turnover)
Glucose Metabolism
Energy Expenditure
Metabolomics
We sell TCA metabolites and enzymes for pinpointing metabolic processes as well as
stable isotope-tagged compounds that can aid in measuring rates of whole body
metabolism or glucose metabolism. Stable isotope-enriched compounds are
metabolically similar to natural homologues, making them safe to use as tracers.