3- Hydroxy-P-methylglutaryl

Knappe, J., Ringelmann, E., Lynen, F. fiber die (3-Hydroxy-p-Methylglutaryl Reduktase der Hefe zur Biosynthese der Xerpen. XI. Biochem. Z. 1959, 332, 195-213. 

A) The condensation of acetoacetyl-CoA with a molecule of acetyl-CoA to yield 3-hydroxy-p methylglutaryl-CoA (HMG-CoA)... 

Hydroxy-P-methylglutaryl coenzyme A reductase (HMG-CoA reductase) is widespread in bacteria, yeasts, higher plants, insects, and mammals and is present in all tissues that synthesize isoprenoid compounds. In mammals, this enzyme is localizied in the endoplasmic reticulum in yeasts, in the mitochondrial matrix and, in plants, both chlo-roplasts and cytoplasm have HMG-CoA reductase activity... 

In the first step, acetate (as a coenzyme A thioester) plus malonate gives acetoacetate, just as for the fatty acids. The next step is a different kind of reaction. Another acetate unit (as malonate) is added via an aldol condensation, using a HMG-CoA synthase enzyme, to give 3-hydroxy-P-methylglutaryl coenzyme A (HMG-CoA). This is reduced by NADPH with a HMG-CoA reductase to mevalonic acid (MVA) in the ratedetermining step for the whole sequence of reactions that builds up the... 

---