Parkinson’s disease ‘may start in gut’

Re:Parkinson’s disease ‘may start in gut’ by cdsx on Sunday December 04, 2016 @11:06PM (#13103300)

Proteins don't usually "learn" how to fold from other proteins, their structure is usually determined by their amino acid sequence. In vivo there are chaperone proteins that help proteins fold into their natural structures by preventing premature aggregate folds, but still their final fold is a result of their amino acid sequence. Less commonly, there are some rare chaperones that cause specific folding that wouldn't otherwise occur, but these are the exception and not the rule. However you are right that prions are an exception here, prions are uniquely misfolded proteins that are amyloid-prone and cause their otherwise normal folded structure to refold into another prion form, leading to a chain reaction of refolding into the prion form for that particular protein. As far as I know there is still a lot of research to be done in order to verify the theories regarding prions.

It doesn't make sense to say newly synthesised proteins arises mostly from amino acid metabolism, metabolism involves both catabolism (breakdown) and anabolism (synthesis). Amino acid degradation results in glucose via gluconeogenesis or cellular energy (ATP), whereas amino acid synthesis is of course what is used for proteins, as proteins are made of amino acids. So yeah, doesn't really make sense. Perhaps you meant to say that newly synthesised protein uses amino acids of which are most often sourced from proteolysis?

As for red blood cells, they don't have any mitochondria, so they only metabolise glucose and other sugars (and anaerobically at that, due to their function of carrying oxygen). They certainly don't metabolise amino acids or proteins, so I'm not sure where you got that idea from.

I hope that helps.

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Re:Parkinson’s disease ‘may start in gut’ by spangry on Tuesday December 06, 2016 @03:10PM (#13117852)

Yeah I oversimplified protein 'chaperoning' for brevity's sake. As for prion recruitment of other proteins leading to amyloid plaque formation in the brain, I concede it's an open question. But my money would be on 'yes' to this hypotheses, given recent studies that have been coming out (except for a particular German one that concluded the opposite based on a mouse model of PD).

I'm probably on the wrong end of the metabolic semantics here; I was specifically referring to hydrolysis (or is the correct term hydrogenation?) occurring in red-blood cells. If this is not considered part of normal metabolic processed then mea culpa. The particular (pro)drug I mentioned (likely) relies on this mechanism to cleave/dissolve a covalent bond between the two constituents of the prodrug, to produce a 'time-release' effect: the constituents being l-lysine and dexamfetamine/dextroamphetamine ('lisdexamfetamine').

For example, here's one of the few serious studies I've been able to find on its metabolism (i.e. not a single dose study that concludes 'yes, this leads to amphetamine in the blood'): http://www.tandfonline.com/doi/full/10.3109/21556660.2013.77... . There was another (better) one somewhere on pubmed, but I can't seem to find it atm (although it was also an in vitro study). I also found this, more general paper, quite interesting (although I'm guessing it's outdated?): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142344/

I admit, my understanding of the process by which amino-acids are synthesised in to proteins in vivo is not the best. I'm actually a little hazy on how I first arrived at the notion that an over-abundance of l-lysine could disrupt the Krebs-cycle. I probably came up with it during one of my long treks across Wikipedia, so it's very likely wrong....

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