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Kreb’s Cycle

The Kreb's cycle (aka Citric Acid cycle or Tricarboxylic Acid (TCA) cycle) converts pyruvate to CO2 and reducing energy (NADH and FADH2) and phosphorylated energy (GTP).

The reduced energy can be used to generate ATP using the electron transport chain in the presence of oxygen. It is a cyclic process in that oxaloacetate reacts with acetyl CoA to form citrate which starts a series of several other reactions. At the end of each cycle, the four-carbon oxaloacetate has been regenerated, and the cycle continues. (Though occasionally the oxaloacetate destabilizes after regeneration.)

2 pyruvate 2 GDP 2 H3PO4 4 H2O 2 FAD 8 NAD+ Kreb's Cycle 6 CO2 2 GTP 2 FADH2 8 NADH
NAD and FAD are rather small nucleotide molecules that are electron carriers.

FAD can transfer its reducing power to FP. The reduced and oxidized forms of NAD are not clear; thus oxidized NAD can be called NADox, NAD+ or NAD. Reduced NAD can be called NADred, NADH or NADH2.

Kreb's Cycle Steps

Citrate FormsThe citric acid cycle begins with Acetyl-CoA transferring its two-carbon acetyl group to the four-carbon acceptor compound, oxaloacetate, forming citrate, a six-carbon compound.
DecarboxylationThe citrate then goes through a series of chemical transformations, losing first one, then a second carboxyl group as CO2.
Most of the energy made available by the oxidative steps of the cycle is transferred as energy-rich electrons to NAD+, forming NADH. For each acetyl group that enters the citric acid cycle, three molecules of NADH are produced.
FADH2Electrons are also transferred to the electron acceptor FAD, forming FADH2.

Kreb's Cycle: Some More Detail

  • The three carbon pyruvate reacts, release a carbon as CO2. The reaction release energy to reduce NAD+ into NADH. The remaining 2C compound binds coenzyme A (coA) to form acetyl CoA. Due to the loss of CO2, this is an irreversible reaction. The binding of coA-SH to the acetyl is likely so that enzymes can more easily act upon the acetyl.
  • The 2C acetyl chain is released from acetyl CoA and binds to the 4C oxaloacetate to make the 6C citrate, a tricarboxylic acid. Enzymes can act uopn the 6C citrate much more easily than a lone 2C acetyl chain. The 2C acetyl will eventually be totally decomposed to again regenerate oxaloacetate. This oxaloacete will be reused.
  • H2O is removed from citrate and H2 is the re-added to regenerate citrate. This reaction rearranges the molecule so that energy can be extracted more efficiently. Citrate is a ketose (it contains a ketone group), but removal of H2O converts it to an aldose (the new chemical contains an aldehyde). When H2O is added back, an isomer of the origiinal citrate (now a ketose again) is formed.
  • The next reaction releases energy to form reduced NADH.
  • The reaction of the 6C oxalosuccinate to the 5C alpha-ketogluterate leads to the release of CO2.
  • The next reaction again utilizes CoA-SH as a handle for one reaction. Energy is also released again as NADH. At this point we also lose the last carbon in the form of CO2. The reaction of succinyl-CoA to succinate leads to a phosphorylation of GDP to GTP. A GTP molecule can be easily converted to an ATP by one more reaction.
  • Succinic acid to fumaric acid yields a reduced flavoprotein. This FADH2 can be passed to FPH2 and used in the electron transport chain (in the presence of oxygen) to presumably yield two ATP molecules.
  • The final step of malate to oxaloacetate wrings out the last bit of energy (as NADH) of our original glucose. The regenerated oxaloacetate is now ready to react with another acetyl CoA, allowing the cycle to run a total of five times.


Glucose may alternatively be from the hydrolysis of intracellular starch or glycogen. In animals an isozyme of hexokinase called glucokinase is also used in the liver, which has a much lower affinity for glucose (km in the vicinity of normal glycemia), and differs in regulatory properties. The different substrate affinity and alternate regulation of this enzyme are a reflection of the role of the liver in maintaining blood sugar levels.


Phosphoglycerate, aka glycerate 3-phosphate (GP) or 3-phosphoglycerate (3PG), is a biochemically significant 3-carbon molecule that is a metabolic intermediate in both glycolysis and the Calvin cycle. This chemical is often termed PGA when referring to the Calvin cycle. 3-phosphoglycerate is the resultant of the split of 6 carbon intermediate that is so unstable it splits instantly. And two 3-phosphoglycerate is produced for each molecule of CO2.

Kreb’s CycleComments