Cholesterol biosynthesis has been exhaustively studied in animals. All steps occur in the cytosol. The starting material is citrate, which is exported by the mitochondrion when metabolic fuels are high. It is converted into acetyl-CoA, ADP, CO 2 , and oxaloacetate by ATP-citrate lyase, together with ATP and CoASH as substrates. Three acetyl-CoAs are converted inoto HMG-CoA by the cytosolic isoforms of thiolase and 3-hydroxy-3-methylglutaryl-CoA synthase. The HMG-CoA is then reduced by NADPH to mevalonate by HMG-CoA reductase, the rate controlling enzyme of cholesterol biosynthesis. This enzyme has 8 helical domains anchoring it in the Golgi membrane of the ER;  the catalytic domain is in the cytosol. It is strongly inhibited by the statins , a class of drugs based on a mold metabolite which, at least at one time, were the largest selling class of drugs in the world. Mevalonate is acted of by a series of 3 kinases to give the highly labile 1,2-diphosphomevalonate-3-phosphate, which is acted on by a lyase to give phosphate, CO 2 , and isopentenyl diphosphate . Isopentenyl diphosphate isomerase converts the latter to the less stable dimethylallyl diphosphate . Farnesyl diphosphate synthase takes one DMAPP and two IPP to give the C 15 metabolite farnesyl diphosphate . There are a large number of additional steps to generate cholesterol from IPP, the ubiquitous precursor of all isoprenoids.
• Enhanced weight loss. There is evidence that DHEA helps promote weight loss in laboratory animals, and perhaps in humans as well, although the results are inconsistent, and it is unclear what the operative mechanism is. It may involve appetite suppression or thermogenesis (fat burning) or both. A curious observation is that, in men who lose weight without DHEA supplementation, the natural levels of this hormone tend to rise. This is not true of women, however - still more evidence of the different ways in which this remarkable hormone is metabolized by the two sexes.
Abnormal GH levels can usually be modified once the causes are identified. Synthetic GH is available to alleviate deficiencies in children (treatment of adults with GHD is more controversial). Combinations of surgery, medication, and radiation can be used to treat pituitary tumors that are causing excess GH production. The important thing is to identify GH abnormalities as soon as possible for good outcomes. If left untreated, a child with GH deficiency will continue to have a short stature compared to peers. Likewise, the bone growth changes associated with gigantism and acromegaly are permanent.