Cholesterol synthesis and
regulation
Cholesterol and the brain
Mammalian brain function is dependent on special-ized membranes
designed for signal transmission. Greater cognitive sophistication in humans
appears to depend on a much greater number of connections and, consequently,
greater potential for signal pro-cessing. Like the membrane lipids of most
other mammalian organs, brain lipids contain a relatively high proportion of
cholesterol, which increases from about 40% of the lipid content in neonates to
nearly 50% in adults.
Unlike other organs, the mammalian brain is prob-ably unique in
being unable to acquire appreciable amounts of cholesterol from the
circulation, i.e., from the diet or from synthesis outside the brain. This has
been extensively studied in the young rat and sup-porting, although
inconclusive, evidence is also avail-able for the pig. The brain has sufficient
capacity to synthesize cholesterol from acetyl-CoA derived pri-marily from
either glucose or ketones. Hence, it achieves the required level of cholesterol
apparently entirely by endogenous synthesis. In neonates, ketones appear to
play a greater role as substrates for brain cholesterol than in adults, in whom
their main func-tion seems to be as an alternative fuel to glucose. Among the
common dietary long-chain fatty acids that would give rise to ketones during
fat oxidation, PUFAs, particularly linoleate and α-linolenate, appear to be the best substrates for ketogenesis,
since carbon from these fatty acids readily appears in brain choles-terol in
suckling rats.
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