- The process of steroid production in living organisms.
Steroid metabolism is the complete set of chemical reactions in organisms that produce, modify and consume steroids. These metabolic pathways include:
- steroid synthesis - the manufacture of steroids from more simple precursors
- steroidogenesis - the interconversion of different types of steroids
- steroid degradation.
Steroid biosynthesisSteroid biosynthesis is an anabolic metabolic pathway that produces steroids from simple precursors. This pathway is carried out in different ways in animals than in many other organisms, making the pathway a common target for antibiotics and other anti-infective drugs. In addition, steroid metabolism in humans is the target of cholesterol-lowering drugs such as statins.
It starts in the mevalonate pathway in humans, with Acetyl-CoA as building blocks, which form DMAPP and IPP. In following steps, DMAPP and IPP form lanosterol, the first steroid. Further modification belongs to the succeeding steroidogenesis.
Mevalonate pathwayThe mevalonate pathway or HMG-CoA reductase pathway starts with and ends with dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP).
Regulation and feedbackSeveral key enzymes can be activated through DNA transcriptional regulation on activation of SREBP (Sterol Regulatory Element-Binding Protein-1 and -2). This intracellular sensor detects low cholesterol levels and stimulates endogenous production by the HMG-CoA reductase pathway, as well as increasing lipoprotein uptake by up-regulating the LDL receptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation.
PharmacologyA number of drugs target the mevalonate pathway:
Plants and bacteriaIn plants and bacteria, the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates., which are a large class of lipids that include the carotenoids, and form the largest class of plant natural products.
Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol. Lanosterol can then be converted into other steroids such as cholesterol and ergosterol. These bile acids can then be eliminated through secretion from the liver in the bile. The expression of this oxidase gene can be upregulated by the steroid sensor PXR when there is a high blood concentration of steroids.