Discussion of Methyl Pyruvate and Alkyl Pyruvates

I should probably not even mention this, given that "some of" these sources are fringe-ish, evidently. But I came across this web site on which people were talking about methyl pyruvate being available as a supplement, and this is not the website but is a link to a google search (http://www.google.com/search?hl=en&num=100&q=%22methyl+pyruvate%22+tablespoon+energy&aq=f&oq=&aqi=). Yeah--that's a teeth-chatterer. It literally causes shivering. Ethyl pyruvate has been much more heavily researched (http://scholar.google.com/scholar?hl=en&q=%22methyl+pyruvate%22+neuron+OR+axon+OR+protect+OR+protective+OR+protection&as_sdt=2000&as_ylo=&as_vis=0), and that'll probably become available eventually. But one issue with either ethyl pyruvate or methyl pyruvate, apart from methyl pyruvate's apparent lability (http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv3p0610) and apparent capacity to undergo polymerization in the presence of a metal catalyst, at least, at room temperature (http://scholar.google.com/scholar?hl=en&q=%22methyl+pyruvate%22+polymerises&as_sdt=2000&as_ylo=&as_vis=0), might be that, at least in the case of methyl pyruvate, the compound(s) can serve as substrates, prior to their deesterification, of alanine aminotransferase, lactate dehydrogenase, and presumably other enzymes that metabolize pyruvate or other alpha-keto acids [Jijakli et al., 1996: (http://www.ncbi.nlm.nih.gov/pubmed/8914921)]. The problem I could imagine would be the loss of stereoselectivity in the conversion of O-alkylpyruvate esters to lactate by lactate dehydrogenase (LDH). LDH normally forms only (S)-lactate (L-lactate) from pyruvate, which is achiral (ethyl and methyl pyruvate are also achiral), but there's some evidence that prokaryotic enzymes, such as xylose reductase, can form both (R)-ethyl lactate and (S)-ethyl lactate from ethyl pyruvate [Kratzer and Nidetzky, 2007: (http://www.rsc.org/delivery/_ArticleLinking/ArticleLinking.asp?JournalCode=CC&Year=2007&ManuscriptID=b616475g&Iss=10)]. The other product, formed by the reaction of ethyl or methyl pyruvate with alanine aminotransferase, would be ethylalanine or methylalanine, I think. But would the L- or D-alkylalanines be formed (or both)? It's possible that there wouldn't be any issues with it. D-lactate is metabolized much more slowly than L-lactate is, although "nanomolar" amounts of D-lactate are supposedly formed, under normal circumstances, by the metabolism of methylglyoxal [Khan and Garner, 2007: (http://www.ramcjournal.com/2007/jun07/khan.pdf)]. In this abstract [Kou and Guan, 2008: (http://www.ncbi.nlm.nih.gov/pubmed/18344089)], ethyl pyruvate improved intestinal barrier function and reduced sepsis-associated elevations in plasma D-lactate, which was of prokaryotic origin (produced by colonic microorganisms) [Schoorel et al., 1980: (http://adc.bmj.com/cgi/reprint/55/10/810.pdf)]. That's a separate issue but could be a source of confusion or something. And then methyl pyruvate's deesterification yields methanol, rather than ethanol (for ethyl pyruvate). Aspartame also yields methanol, upon the deesterification of its methyl ester moiety (Jijakli et al., 1996). There's all this research saying that the amounts of methanol derived from aspartame aren't damaging, etc., but I dunno. "Slurping wood alkey (wood alcohol, a.k.a. methanol) dudn't sound too good to meeeeeee. I'm not saying I won't take a nip, because I like the taste of that s#$&, but..." It's probably not a very large amount, but anyway...My main concern would be the potential for racemic products to be formed, but it's possible that the eukaryotic and mammalian enzymes retain their stereoselectivity/enantioselectivity in the utilization of alkylpyruvates as substrates. Here's a search to potentially answer that question (http://scholar.google.com/scholar?hl=en&q=NADH+%22ethyl+pyruvate%22+%22R-lactate%22+OR+%22D-lactate%22+OR+%22%28R%29-lactate%22+OR+%22ethyl+R-lactate%22+OR+%22ethyl+D-lactate%22+OR+%22ethyl+%28R%29-lactate%22&as_sdt=2000&as_ylo=&as_vis=0), but I can't address the question to an adequate degree. Then, I wonder if there could be the acyl-glucuronidation-mediated-conjugation issue, etc. These authors discuss some of their research that had shown ethyl pyruvate to be a substrate/competitive inhibitor of glyoxylase-1 [Santel et al., 2008: (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567432/pdf/pone.0003508.pdf)], and, given that D-lactate is a product of glyoxylase enzymes and that GSH is a cofactor and that GSH has sometimes been shown to be depleted, evidently in association with therapeutic effects [Zingarelli, 2004: (http://critcaremed.org/pt/re/ccm/pdfhandler.00003246-200407000-00022.pdf)], by ethyl pyruvate, it follows that some ethyl pyruvate may well be a substrate of glyoxylase-1 and that D-ethyllactate and, by extension, D-lactate, upon the deesterification of D-ethyllactate, might be formed as products of the reaction(s). The metabolism of methanol consumes GSH, though, too, by some relatively specific mechanism and acetaldehyde could, presumably, produce some of that effect. Alkylpyruvates and other acyl esters of nutrients can, incidentally, serve as substrates for a lot of different enzymes with esterolytic activity, such as carbonic anhydrase enzymes, in the case of methyl pyruvate [Pocker et al., 1978: (http://scholar.google.com/scholar?hl=en&q=%22methyl+pyruvate%22+%22carbonic+anhydrase%22&as_sdt=2000&as_ylo=&as_vis=0), etc.]. In any case, these issues may not be issues at all, but it was something to think about.