Blockage of the cholesterol synthetic pathway affects not only cholesterol synthesis but also other processes, such as the synthesis of isoprenoids, lipid intermediates necessary for protein prenylation; dolichol
phosphate, which is involved in protein glycosylation; and ubiquinone, which is involved in respiratory chain activity.
In addition to the effects on cholesterol biosynthesis, statins regulate the synthesis of various other major products such as dolichol
, geranyl pyrophosphate, and farnesyl pyrophosphate.
SRD5A3 is required for converting polyprenol to dolichol
and is mutated in a congenital glycosylation disorder.
The oligosaccharide was released from dolichol
pyrophosphate by mild acid hydrolysis, studied by [sup.1]H-NMR and the structure compared to that deduced for other organisms.31) The reducing N,N-diacetylchitobiose unit and nine mannose residues are present, the latter in equimolar amounts.
The inhibition of the enzyme HMG-CoA reductase, an essential key in the biosynthesis of cholesterol (Medina 2010; Musso et al., 2011), demonstrates to be the key point to reduce cholesterol and several compounds like isopentenyladenine, dolichol
, ubiquinone, geranilpirofosfato (GGPP), farnesylpyrophosphate (FPP) (Wong et al., 2007; Gauthaman et al., 2009).
Branch point regulation is an important mechanism controlling carbon flow in the MVAP; the FPP produced by the MVAP can be shunted to many metabolic branches for the synthesis of critical molecules such as ubiquinone, dolichol
, or prenylated proteins .
Isoprenoid includes cholesterol, bile acids, steroid hormones, dolichol
, ubiquinone, prenylated proteins, and a wide variety of plant terpenoids .
The lipid dolichol
used as a carrier in the first stage of N-glycosylation is a polymer of isoprene units (C[H.sub.3]C(C[H.sub.3])=CH-C[H.sub.2]-) predominantly of 14-17 units in the baker yeast , 19-22 in humans , and of undetermined length in Candida.
Guan believes dolichol
profiling could effectively distinguish RP caused by DHDDS mutation from that caused by other mutations.
Branch-point reactions in the biosynthesis of cholesterol, dolichol
, ubiquinone and prenylated proteins.
These isoprenoid lipids are the building blocks for the production of a variety of metabolites, such as dolichol
and ubiquinone, but are also required for posttranslational modification (prenylation) of proteins, including small GTPases .
The alteration in cell function resulting from the inevitable inhibition of CoQ10 and dolichol
is giving us the rest of our broad list of incapacitating adverse effects--the rhabdomyolysis (breakdown of muscle fibers), permanent myopathy (dysfunction of muscle fibers), permanent neuropathy (damage to peripheral nerves) and ALS-like neuromuscular degeneration that has placed many hundreds in wheelchairs--yours truly included.