The authors of this article [McGivan et al., 1977: (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1164578) (http://www.ncbi.nlm.nih.gov/pubmed/849273)] discuss the way in which the activity of ornithine aminotransferase (OAT), a mitochondrial enzyme, is reversible but normally operates in the direction of the breakdown of ornithine. This is consistent with the explanation given by Inubushi et al. (2005) [Inubushi et al., 2005: (http://www.ncbi.nlm.nih.gov/pubmed/16179747)] for the impairments in collagen formation that occur in response to pyridoxine depletion. The products of ornithine degradation via OAT are glutamate-gamma-semialdehyde and glutamate, and evidently glutamate-gamma-semialdehyde undergoes a nonenzymatic isomerization to pyrroline-5-carboxylate (P5C) (McGivan et al., 1977). The P5C can then be reduced to proline by pyrroline-5-carboxylate reductase [Smith et al., 1980: (http://www.pnas.org/content/77/9/5221.full.pdf+html) (http://www.ncbi.nlm.nih.gov/pubmed/6933554?dopt=Abstract)]. Apparently P5C can also be biosynthesized enzymatically, by the coupled activities of two enzymes (gamma-glutamyl kinase and gamma-glutamyl-phosphate reductase), collectively known as "P5C synthase" [Hu et al., 1999: (http://www.jbc.org/cgi/content/full/274/10/6754) (http://www.ncbi.nlm.nih.gov/pubmed/10037775?dopt=Abstract); Smith et al., 1980]. This type of thing helps to show the hazards of supplementing with some single amino acids. You have to know what you're doing, and the authors of this article [Bertolo and Burrin, 2008: (http://jn.nutrition.org/cgi/content/abstract/138/10S-I/2032S) (http://www.ncbi.nlm.nih.gov/pubmed/18806120?dopt=Abstract)] discuss the compartmentalized nature of proline and glutamate interconversions. In theory, one can be converted into the other, but the tissue-specific patterns of expression of different enzymes means that the interconversions are really tissue-restricted and regulated.
Ornithine, in particular, has a long history of being somewhat problematic as a supplement, for use in growth hormone release, etc. It tends to really disrupt the normal creatine biosynthetic pathway, by producing a mass action effect on arginine:glycine amidinotransferase activity that favors glycine and arginine accumulation. This reduces guanidinoacetate production and can reduce creatine biosynthesis at various locations that depend on, for example, renally-derived guanidinoacetate. That information about proline and pyridoxine (vitamin B6) (http://hardcorephysiologyfun.blogspot.com/2009/01/pyridoxine-collagen-and-vascular.html) might appear to suggest that ornithine could enhance collagen biosynthesis, but this is probably not the way it would work. Ornithine could be converted into other metabolites and reduce collagen formation by some strange mechanism. Single amino acid supplementation tends to be just not great and not work out so well. Arginine is safer than ornithine, from the standpoint of the urea cycle, but arginine is a substrate for both endothelial nitric oxide synthase (eNOS) and the unregulated inducible nitric oxide synthases (iNOS). An increase in iNOS-derived nitric oxide would tend to worsen inflammation and inhibit the activities of respiratory chain enzymes. There are exceptions, though, I guess. In people with inherited metabolic disorders, prescribed amino acid combinations can be like an art form.
Barbul (2008) [Barbul, 2008: (http://jn.nutrition.org/cgi/content/abstract/138/10S-I/2021S) (http://www.ncbi.nlm.nih.gov/pubmed/18806118?dopt=Abstract)] discusses the fact that either ornithine or arginine could conceivably be used to enhance collagen formation, and there's some research showing that exogenous proline or other amino acids can be antiatherogenic. Arginine would be safer than ornithine, but that doesn't sound very good to me. Using something like vitamin B6 to increase proline availability seems more reasonable to me. There's research showing that inadequate protein intake ("protein energy malnutrition") contributes to things like anemia in elderly people, and any degree of physical activity can increase the protein requirement to some extent. There's still some controversy about protein requirements, but that seems to me to be a better way to get amino acids (from protein in foods).
That article by Barbul et al. (2008) mentions that collagen is one-third glycine, and reduced folates and cobalamin could reasonably be expected to maintain glycine availability for collagen biosynthesis. But using exogenous glycine (glycine supplementation) would probably not be a good idea, because the cell culture and animal studies show the way an excess of glycine can have really unpredictable and undesirable effects on one-carbon metabolism (on the folate cycle and the S-adenosylmethionine/S-adenosylhomocysteine ratio, etc.). But there's a long history of elevated homocysteine levels being associated with reductions in collagen formation. A lot of the association was thought to be relevant only in people with genetic hyperhomocysteinemia (in which the drastically-elevated levels of homocysteine form disulfide links with collagen-producing enzymes or something), and it's likely to be the case that extreme hyperhomocysteinemia will produce different and more severe derangements in collagen formation than milder, more physiological elevations in homocysteine will. But there are recent articles discussing the role that the activities of serine hydroxymethyltransferase isoforms (major folate cofactor-dependent enzymes) have in maintaining glycine availability (via serine, etc.) for collagen formation and other glycine-consuming reactions (http://scholar.google.com/scholar?num=100&hl=en&lr=&q=%22serine+hydroxymethyltransferase%22+collagen+folate). An excess of exogenous glycine, for example, could all be converted into sarcosine or could cause serine to accumulate abnormally, and there may be some "sophisticated" coupling mechanisms that allow serine hydroxymethyltransferase to interact directly with enzymes that use serine or glycine. This could produce some kind of channelling effect that wouldn't be replicated by supplying a lot of exogenous glycine.
Even though there appear to be more articles discussing the direct effects of wild elevations in homocysteine (past normal physiological levels) on collagen cross-linking (http://scholar.google.com/scholar?num=100&hl=en&lr=&q=homocysteine+collagen), that's probably not the major mechanism that would occur in a person who doesn't have either a genetic disease or some extreme elevation in serum homocysteine. That was the original hypothesis that they refer to, though ("McKusik's hypothesis"), to explain the collagen abnormalities associated with hyperhomocysteinemia. There's a book by one of the original researchers on homocysteine, and it may be that McKusik. The book was targeted to the general public and came out about 10 years ago, but the author discusses all of the pathological differences between atherosclerosis resulting from hyperhomocysteinemia and from other causes. It's a really interesting book, actually, even if homocysteine has turned out to be, to a large extent, a surrogate marker or proxy for disturbances in other one-carbon-related pathways, such as thymidine and hypoxanthine formation, that accompany hyperhomocysteinemia.
There's actually a lot of research showing reductions in collagen biosynthesis in response to pyridoxine depletion. Masse et al. (1996) [Masse et al., 1996: (http://www.ncbi.nlm.nih.gov/pubmed/8805998)] found that pyridoxine deficiency produced changes in the collagen content of bones, but I'm not entirely clear on what changes the authors found. The pyridoxine deficiency caused decreases in the "fracture loads" and "offset yields" of the bones and only affected the collagen but didn't affect mineralization. I don't know how to interpret their data, and reading up on the ways of evaluating the tensile properties of bone doesn't really appeal to me at the moment. It's interesting, though, and Masse et al. (1996) discuss the interaction of pyridoxine with alkaline phosphatase activity. It seems like the effects of pyridoxine on bone and connective tissues is mainly due to an improvement or increase in collagen formation and isn't the result of changes in serum calcium. There's a lot of research showing that pyridoxine can reduce oxalate formation, I think, and thereby reduce renal calcification or reduce the incidences of calcium oxalate stones, I think, under some circumstances. But I don't know what the mechanisms are in that area.
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