(chirality, chemistry), Could normal cells consume the D aa and then covert it to L aa for building proteins and cell use. On the other hand, could cancer cells consume D aa and not be able to convert it to L aa.?
Many references mention that "Only L-amino acids are manufactured in cells and incorporated into proteins."
Hi Taissir, in order to change D-aa to an L-aa, you will have to have to have an enzyme that is an "aa-isomerase".
I cant find any specific reference whether this enzyme exists, but I did find a reference on how bacteria convert D-Phe to L-Phe.
http://www.ncbi.nlm.nih.gov/pubmed/14339270
Eukaryotes do produce the enzyme d-Amino-acid oxidase which converts the amino acids to a non-chiral 2-oxo acid. This metabolite could then be used for biosynthesis of certain l-amino acids.
This enzyme is more active on some amino acids than others and is unlikely, in normal cells, to be present in large amounts as d-amino acids are low abundance.
I would be surprised if cells could live if only fed d-amino acids- there are certain amino acids, eg histidine and tryptophan which mammals cannot synthesise. In these cases, the d-form might be metabolised, but the l-form couldn't be made.
Generally "Only L-amino acids are manufactured in cells" but there exist some specific enzymes which change the chirality of a specific l- to a specific d- amino acid serine and aspartate racemases will convert l-ser and l-asp to the d-form as these are used in some signalling roles.
thank you, obviously (?) there is interconversion among the L, D in cells to certain extent. However, the attached article, might, indicate that cancer cells do produce D aa. The reason may be is the rapid cell growth and the lose of "higher function(s)".(?) I still could not find if cancer cells can live off D aa even for one aa. While if the other normal cells can live on D aa; at least for the treatment period. ? The reason I am following this question is because it seems that cancer cells, could have lost many of the metabolic abilities that normal cells have. This might show in their inability i.e. the cancer cells, to metabolize the D aa while normal cells can, probably, at least to some extent. ?
http://www.ncbi.nlm.nih.gov/pubmed/9949871
Hi Taissir, the link you posted is a review article from 1998. It concluded with:
"Some D-amino acids may originate in foods consumed, but it is uncertain whether enzyme systems are able to incorporate D-amino acids into tumor proteins during growth. Nevertheless, if significant levels of D-amino acids were to be found in tumor proteins, the implications could be far-reaching. Confirmation of the presence of D-amino acids at any concentration in tumors would provide new insights into the mechanism for autogenesis and maintenance of tumors."
" May, If, Could, Would" are not words that inspire confidence in this research topic.
If there are no reproducible experiments and data to support this hypothesis, it is worthless.
I forgot to add this from the link you posted:
"However, more than 40 years later the development of much more refined analytical techniques for the resolution and detection of amino acid enantiomers provided more definitive evidence that D-amino acids are not common to all tumor tissues and probably are not integral to the cancer process. This is not surprising when one considers that a tumor consists of fast-growing cells. Thus, there would not be sufficient time for any L-amino acid to racemize to the D isomer."
" I still could not find if cancer cells can live off D aa even for one aa. While if the other normal cells can live on D aa; at least for the treatment period. ? "
For the non-essential amino acids, any cells can live without the L-form (as it will just synthesise it) but for the essential amino acids, deprivation of the L-form will result, ultimately, in death.
Of course there's a faint possibility that a given cancer line might have gained some mutation which gives it a racemase functionality, but its really very unlikely.
But actually I doubt that it is possible to deprive the cell of L-amino acids in vivo due to the body's inherent protein turnover. We know that in a protein deficient diet, the body starts catabolising the muscles to scavenge protein, so I can't see how you could get the cells to even try and live on D-amino acids during any in vivo treatment period.
can we then give a mixed diet (D aa to L aa) to minimize the cancer cell growth, assuming cancer cells can't or wont be able to metabolize D aa while normal cells can. With the ratio and objective to prevent normal cell starvation and realizing the normal cell can, to a certain degree, utilize D aa. On the other hand the question of essential aa still there. Another point is that: when do the normal cells starts to catabolizing e.g. muscles to scavenge protein i.e. is it before or after trying or using D aa. In other words: do normal cells under starvation prefer to catabolizing other cells e.g. muscles cells or they will go for D aa if available and then if no D aa nor L aa they go into catabolizing other cells.? In this question I am counting on the loss of some or most capabilities of cancer cells to perform "higher normal cell function(s)." I also attached a link on how also this way of thinking might help in pancreatic cancer diagnosis.
http://www.nlm.nih.gov/medlineplus/news/fullstory_148616.html
http://www.nature.com/nrendo/journal/vaop/ncurrent/full/nrendo.2014.171.html?WT.mc_id=FBK_NatureReviews
Taissir, cancer cells and normal cells have the same metabolic pathways. In other words, if you starve cancer cells, you will also starve normal cells.
As for your attached link, the branched-chain amino acids (BCAA) are mainly Ilu, Val and Leu. These are essential amino acids. They are not synthesized by humans.
If you deprive the body of these essential aa's by giving the D isomers, you will deprive normal cells of these essential aa's as well.
And as Matthew said, the body will start to scavenge proteins from existing tissues to fulfill the need for these essential aa's.
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