Isocitrate dehydrogenase

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Identifiers
Symbol(s)	IDH1
Entrez	3417
OMIM	147700
RefSeq	NM_005896
UniProt	O75874
Other data
EC number	1.1.1.42
Locus	Chr. 2 q32-qter

Isocitrate dehydrogenase (EC 1.1.1.42), also known as IDH, is an enzyme which participates in the citric acid cycle. It catalyzes the third step of the cycle: the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO₂ while converting NAD⁺ to NADH. 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. Another isoform of the enzyme catalyzes the same reaction, however this reaction is unrelated to the citric acid cycle, is carried out in the cytosol as well as the mitochondrion, and uses NADP⁺ as a cofactor instead of NAD⁺.

The CAS number for this type of the enzyme is [9028-48-2].

1 Energetics:
2 Structure:
3 Regulation:
4 See also

[edit] Energetics:

The overall free energy for this reaction with either isoform is -8.4 kJ/mol. IDH lowers the K_m (Michaelis constant) of isocitrate without lowering the V_max (maximum reaction rate - see Michaelis constant for more details).

[edit] Structure:

The structure of human IDH has been determined. It is known that the protein is composed of 3 subunits, is allosterically regulated, and requires an integrated Mg²⁺ or Mn²⁺ ion. The closest homologue which has a known structure is the E. coli NADP-dependent IDH, which only has 2 subunits and a 13% identity and 29% similarity based on the amino acid sequences, making it a far cry from human IDH and not suitable for close comparison.

[edit] Regulation:

The IDH step of the citric acid cycle, due to its large negative free energy change, is one of the irreversible reactions in the citric acid cycle and therefore must be carefully regulated to avoid unnecessary depletion of isocitrate (and therefore an accumulation of alpha-ketoglutarate). The reaction is stimulated by the simple mechanisms of substrate availability (isocitrate, NAD⁺, Mg²⁺ / Ca²⁺ ), product inhibition (by NADH and alpha-ketoglutarate), and competitive feedback inhibition (by ATP).