dissolve in hot water

August 8, 2012 6:48 PM

does mixing creatine in hot water denature it?

some posts on training forums suggest that creatine should not be mixed in hot water because it will denature.

I suspect this is just a guess, that forum posters are assuming that because creatine in synthesised from three amino acids, that it will behave like a protein.

I suspect the guess is wrong, that the kind of temperature induced conformational changes that can occur in a large complex protein, don't apply to a molecule as simple as creatine, and even if they did they would be reversible.

But there could be other reasons that creatine might be degraded by hot water.

Anyone want to drop some chemistry on this?

posted by compound eye to Science & Nature (10 answers total)

Response by poster: i realise there are many forums posts discussing this topic, but I don't trust the internet, i only trust metafilter.
posted by compound eye at 6:53 PM on August 8, 2012 [7 favorites]

Best answer: I find it very hard to believe that a molecule so small has any secondary or tertiary structure to denature, or that even if it did, that it would have any relevance to its role as a metabolite.
posted by grouse at 7:25 PM on August 8, 2012 [5 favorites]

Best answer: I also can't find any mention of this in the biomedical literature.
posted by grouse at 7:26 PM on August 8, 2012 [2 favorites]

Best answer: I am no chemist, but what jumps out at me looking at the structure is the potential for cyclization. When I googled that, I found this thesis:
http://www.marshall.edu/etd/masters/diamond-brian-2005-ma.pdf

I will have a closer look later myself, but it looks like this might answer your question better than I can....
posted by Tandem Affinity at 7:46 PM on August 8, 2012 [1 favorite]

Best answer: As Tandem Affinity says, probably what these folks are talking about is conversion to creatinine, "a spontaneously formed cyclic derivative of creatine." This is not denaturization, it is (if my somewhat rusty chemistry still works) simple hydrolysis, and certainly could happen at an appreciable rate to creatine just hanging out in water. This rate would increase with temperature.
posted by pullayup at 7:49 PM on August 8, 2012 [2 favorites]

Best answer: According to this older paper, it occurs at a rate of 1.06-1.33% per day in vitro (that is, just mixed with water outside of any biological system) at 38 C.
posted by pullayup at 7:53 PM on August 8, 2012 [1 favorite]

Best answer: Thanks for the expansion, pullayup! I also forgot to mention that this sort of thing is a danger for most peptides, regardless of their size. In the lab, peptides are kept as dry as possible, under nitrogen or argon (to prevent oxidation), and deep frozen....all to prevent the inevitability of hydrolysis.
posted by Tandem Affinity at 7:56 PM on August 8, 2012 [2 favorites]

Response by poster: wow these answers just keep getting better
posted by compound eye at 9:28 PM on August 8, 2012

Best answer: I found a 2011 review in Amino Acids that basically confrims what TA and pullayup said (source). Basically although it's extremely stable even at high temperatures (60 deg C) as solid creatine monohydrate, the higher temperatures and lower pHs (increased acidity) that promote its dissolution in water also accelerate its degradation into creatinine. The available salts are less stable in their solid forms but both dissolve better and degrade more quickly. But the article talked about dissolution temperatures up to 60 deg C, and said, "If creatine is not consumed immediately after it has been dissolved in water, it should be stored at a low temperature to retard the degradation." I think that means you can safely use hot-but-not-boiling water. (We create creatine from its constituent amino acids in our kidneys and livers, and schlep it around to our musculature, at 37-38 deg, so it can't be that heat-sensitive.)

(Denaturation is a different business, as grouse points out - its tripeptide chain is too short to bend much, or fold, so creatine really doesn't have any secondary or tertiary structure to destroy.)
posted by gingerest at 9:49 PM on August 8, 2012 [1 favorite]

Response by poster: Tandems link mentions that this has interested researchers since the 1920's.
It's true : http://www.biochemj.org/bj/022/0920/0220920.pdf

Thanks for the excellent answers.
posted by compound eye at 10:45 PM on August 8, 2012