Hydroxymethylglutaryl-coenzyme A synthase C-terminal <p>Synonym(s): 3-hydroxy-3-methylglutaryl-coenzyme A synthase, HMG-CoA synthase.</p><p> Hydroxymethylglutaryl-CoA synthase (<db_xref db="EC" dbkey="2.3.3.10"/>) catalyses the condensation of acetyl-CoA with acetoacetyl-CoA to produce HMG-CoA and CoA, the second reaction in the mevalonate-dependent isoprenoid biosynthesis pathway. HMG-CoA synthase contains an important catalytic cysteine residue that acts as a nucleophile in the first step of the reaction: the acetylation of the enzyme by acetyl-CoA (its first substrate) to produce an acetyl-enzyme thioester, releasing the reduced coenzyme A. The subsequent nucleophilic attack on acetoacetyl-CoA (its second substrate) leads to the formation of HMG-CoA [<cite idref="PUB00036056"/>].</p><p>HMG-CoA synthase occurs in eukaryotes, archaea and certain bacteria [<cite idref="PUB00036057"/>]. In vertebrates, there are two isozymes located in different subcellular compartments: a cytosolic form that is the starting point of the mevalonate pathway (leads to cholesterol and other sterolic and isoprenoid compounds), and a mitochondrial form responsible for ketone body biosynthesis. HMG-CoA is also found in other eukaryotes such as insects, plants and fungi [<cite idref="PUB00036058"/>]. In bacteria, isoprenoid precursors are generally synthesised via an alternative, non-mevalonate pathway, however a number of Gram-positive pathogens utilise a mevalonate pathway involving HMG-CoA synthase that is parallel to that found in eukaryotes [<cite idref="PUB00036059"/>, <cite idref="PUB00036060"/>].</p><p>This entry represents the C-terminal domain of HMG-CoA synthase enzymes from both eukaryotes and prokaryotes.</p>