This article [Gibbons, 2003: (http://www.ncbi.nlm.nih.gov/pubmed/14559068)] is good, and the author discusses some interactions, in terms of the HMG-CoA and acetyl-CoA availabilities, of the overall, de novo cholesterol and fatty acid biosynthetic pathways. The author provides an "equation" that is evidently meant to allow one to get a sense of the ways the overall cytosolic HMG-CoA concentration changes in response to changes in the cytosolic acetyl-CoA/(free)CoA ratio. This is it:
[HMG-CoA](cytosolic) = kapp [acetyl-CoA]^3/[CoA]^2
(or, rather, is proportional to) [Acetyl-CoA]^3/[CoA]^2
So the author says that a doubling of the cytosolic acetyl-CoA concentration, without any change in the free CoA concentration, would cause the cytosolic HMG-CoA concentration to increase by a factor of 8. I think there's probably something to that, but I don't know why it's necessary to have an equation. The author also cites research showing that the flux of cytosolic acetyl-CoA into de novo fatty acid formation is ten times the flux, in the liver, of acetyl-CoA into cholesterol formation.
The author also mentions some interesting research on the regulation of HMG-CoA reductase, the so-called rate-limiting enzyme in de novo cholesterol formation, by AMPK. Evidently, pharmacological AMPK activation tends to decrease the HMG-CoA reductase activity in cells, such as the liver, and also decreases de novo fatty acid formation from acetyl-CoA. I haven't read much of the research on the interactions of AMPK and cholesterol metabolism, and it's a lot more complex than that. But that's an important mechanism.
That's relevant to research showing cholesterol depletion from the brains of people who died by violent suicide (there's a whole series of articles showing that violent suicide but not nonviolent suicide is associated with reductions in cholesterol levels in various parts of the brain, at autopsy). That doesn't necessarily mean that the reduction in cholesterol per se was the problem, however, because mitochondrial dysfunction in astrocytes, for example, could reduce citrate export from the mitochondria and hence reduce both astrocytic ketogenesis and cholesterol biosynthesis, etc. I came across this whole series of articles discussing the fact that plasma free fatty acids essentially don't reach neurons, to a significant extent, because the astrocytes utilize them and are in close apposition to the basolateral membranes of cerebral blood vessels. I don't have time to link to them now, but that's an important distinction, for a number of reasons. There are countless articles stating that FFAs are important energy substrates or even the most important energy substrates for astrocytes, and then there are articles that just proclaim that beta-oxidation doesn't occur in the adult brain. It just doesn't even sound plausible, from the standpoint of "common sense" or a general sense of the brain and of cells in general, to think that no cells in the brain would be capable of oxidizing fatty acids. Given that FFAs cross the blood brain barrier by passive diffusion (Cullingford et al., 1999, cited below), what would happen to all the FFAs entering the brain? Do they just accumulate in cells or diffuse back out? How is it that they don't form micelles? It just doesn't make sense, in my opinion, because all cholesterol would then have to be formed from glucose or amino acids, most of which are poor lipogenic substrates, or lactate, which is evidently a good lipogenic substrate, or from the relatively low levels of plasma ketones.
Whenever I see an article with a title saying something "does not" occur or a statement expressing a "strict rule," having to do with just about anything, I tend to immediately suspect that the statement or article will have major flaws, on closer examination of the issue. Things just do not tend to work in a rigid, "tightly-regulated," yes-or-no manner. That's just my obnoxious statement for the day, but it tends to be the case. Another possibility is that the statement itself is sort of correct but misses the point. For example, some of the research showing no passage of deuterium-labeled cholesterol from the blood to the brain seems to have given people the impression that changes in plasma cholesterol have no influence on brain functioning. That's not the case, and there are many mechanisms by which changes in serum cholesterol could strongly influence the brain. I've also read articles, related to Alzheimer's disease, in which the authors discuss their suspicion that some cholesterol does enter the brain from the blood. Researchers tend to dismiss the research (on the basis of 40-year-old studies using acute dosages of deuterium-labeled cholesterol) showing LDL translocation across both the luminal and abluminal membranes of cerebral vascular endothelial cells. I still think most cholesterol is made de novo in the brain, but the small fraction that may not be made in the brain could nonetheless become significant under some conditions. Moreover, researchers have almost always generalized from research in healthy animals to animals or humans in disease states. It may well be that there is an increase in the uptake, into the brain, of plasma lipoprotein-bound cholesterol in response to a brain injury, etc.
Another thing that is noteworthy is that plasma FFAs consist of mostly palmitate and oleate and one other common fatty acid. I forget which one, but plasma FFAs tend to be either saturated or at least "not-highly-unsaturated." In contrast, the FFAs that are liberated in response to cerebral ischemia can be these highly reactive, polyunsaturated fatty acids and can produce much more severe damage than saturated fatty acids can. That's my sense of it, anyway. This is one of the articles [Cullingford et al., 1999: (http://www.ncbi.nlm.nih.gov/pubmed/10709651)] that discusses the fact that astrocytes probably use a lot of plasma FFAs because of the close proximity of the astrocytes to cerebral blood vessels. The perivascular endfeet of astrocytes maintain and, to some extent, constitute part of the blood-brain barrier. That article also discusses research showing that meningeal fibroblasts can produce ketones, and meningeal fibroblasts are also present in the adult brain.
There is, however, the fact that intermediates in cholesterol biosynthesis tend to cause problems, when they accumulate, and so the provision of a lot of ketones or FFAs might, under some circumstances, just cause a lot of intermediates in cholesterol biosynthesis to accumulate and cause problems.
Gibbons (2003) also mentioned that an increase in membrane cholesterol is thought to reduce the membrane "permeability" to sodium and reduce ATP consumption by that "mechanism," but I'm not sure how that's supposed to occur. I remember reading that, many years ago, but I'm not sure if there's any quantitative or definitive data on it. It could be an important mechanism, and then it could be more of a theoretical possibility.
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