10 replies to this topic

[cesium]

I have noticed that within the life extension community that anti-glycosylation supplements such as carnosine, aminoguanidine, Alt-711 ect are very popular, yet it is never acknowleged that some glycoproteins are essential molecules in the maintenance of health and are an integral part of cells membranes, body fluids (such as plasma ) and in mucins. Certain glycans and glucoproteins are also suspected of playing a critical role in cellular signaling and are a component of some of the immunoglobulins. Hell, even the popular supplement Lactoferrin is itself a glycoprotein. Essentially my question is there a point at which severely inhibiting glycosylation proves detrimental to maintaining optimal health?

[scottl]

Cesium (hmm interesting name),

Non-enzymatic glycosylation is one of the primary mechanisms of aging. Do you know for a fact that the supps listed above inhibit the formation of the glycoproteins or is it possible that being proteins that are part of a normal healthy body that these are catalyseed by enzymatic reactions that are unaffected by those supps?

[cesium]

Scottl, you appear to be making a distinction between enzymatic and non- enzymatic glycosylation suggesting that it is only non-enzymatic glycosylation that causes pathological changes, whereas those catalysed by enzymes are somehow natural and therefore beneficial. This study tends to refute that idea:

http://www.pubmedcen...ubmedid=7560067

I know Alteon claims that ALT-711 does not disrupt the natural enzymatic glycosylation sites or peptide bonds in collagen ( though I have yet to see the research that verifies this claim), but my concern is that consuming a variety of these anti-glycosylation supplements may inhibit the body's synthesis of important glycoproteins, some of which recent research implies might be important in immune modulation and other cell signaling pathways.

[Cyto]

When polypeptides destined for secretion or PlasMem. contiguity are pulled into the ER translocon, oligosaccharide transferase moves over an N-Glycan branch from a dolichol phosphate anchor. The action of this oligosaccharide moving over to the Asn-X-Thr/Ser sequence doesn't form the pathological carbonyl group(CO). When it’s done at the Golgi and has the sialic acid caps there is no wild carbonyl group around for unfavorable interactions. Carnosine looks as if it is helping to lower the Gibb's free energy of perturbed protein, encourage denaturation and to "cap" the CO from interacting with other proteins in the already crowded environment. The large hydrophilic branch also acts as a physical block for the base and once folded the domains around the N-Gylcan would also act concomitantly with the structure to further blockage. During a time of exposed carbonyl groups interactions of HSC70-CHIP-BAG should be setting up for lysis of the protein, which should be detected as missfolded. If exposed carbonyls are in the lumen of the ER then calnexin-EDEM-p97(Ufd1-Npl4) should be setting up for the lysis.

And yes the CO group interating with other proteins would build up aggregates over time, I don't consider the systems perfect. I think the short answer here is that carnosine seems to act only on ectopic glycoprots.

[Cyto]

Oh, and no carnosine doesn't have any allosteric/steric inhibition of the glycation machinery otherwise we wouldnt have concentrations of ~20mM in muscle.

[scottl]

Bates,

Thanks--it is good to have a biochemist in the house when you need one.

Cesium,

FWIW I don't take ALT-711.

If you wish to take....experimental supps I believe Lynx has some pets taking...NhBT or whatever it is called that might be of interest (different mechanism).

[lynx]

Yes, my hamsters love NtBHA.

[cesium]

Bates, thanks for elaborating as to the biochemical processes involved. Quite frankly I was never too concerned with the natural substances used as anti-glycosylation supplements such as carnosine or the B vitamine derivatives, rather it is the xenobiotic agents such as Alt-711 and NtBHA that I am a bit leery of using.

[cesium]

scottl, as you have correctly surmised I have been considering the idea of incorporating some of the more esoteric anti-glycosylation supplements into my regimen, and my purpose in posting this thread was to provoke discussion and examine the pros and cons of such an undertaking. Personally I am still somewhat reluctant about taking the plunge, at least until I am able to take the time and educate myself a little better on the subject.

[scottl]

Cesium,

IMHO I would not even consider any of them unless one's diet and supp regimen in other areas were in impeccable order (no idea if yours are or are not).

If you are open to it, why don't you post an idea of your goals along with diet and supps you are taking now.

If you just wish more info then Paul Wakfur (the morelife guy) has some pages that are relevant: http://morelife.org/researchems/

[lynx]

Spin traps, like NtBHA are not anti-glycating agents per se, rather anti-oxidants which don't become pro-oxidants. Bruce Ames found NtBHA to be the most potent mitochondrial anti-oxidant tested and will sub quite nicely for R-ALA in an ALCAR regimen.
Pharmaceutical companies are hot on the trail of novel Spin Traps which are broadly patentable, thus more profitable. Price gouging opportunities in composition of matter patents are much better than in novel use.