Seeking info on Amino acids' effect on GI absorption...

[Jamshyd]

Now I understand that certain amino acids compete with certain others for absorption from the gut through a rate-limiting process. I have the basic idea of how this rate-limiting process works, but I'm not sure about the specifics.

So what I'm looking for is some kind of comprehensive chart or table (or any kind of organised information) about which amino acids interact with which, and how much of each can be taken before they start blocking each others' absorption.

Also, is it that some amino acids are "prefered" more by the transporters therefore there is a hierarchy of absorption, or is it a kind of first-come, first-serve basis?

And another important matter, how much of an effect do amino acids have on certain drugs that depend on these transporters, for example: gabapentin?

I've always sucked at understanding things related to pharmacokinetics, and this is no exception...

I appreciate any info, but err... try to make it organized .

 

[raybeez]

Now I understand that certain amino acids compete with certain others for absorption from the gut through a rate-limiting process. I have the basic idea of how this rate-limiting process works, but I'm not sure about the specifics.

So what I'm looking for is some kind of comprehensive chart or table (or any kind of organised information) about which amino acids interact with which, and how much of each can be taken before they start blocking each others' absorption.

Also, is it that some amino acids are "prefered" more by the transporters therefore there is a hierarchy of absorption, or is it a kind of first-come, first-serve basis?

And another important matter, how much of an effect do amino acids have on certain drugs that depend on these transporters, for example: gabapentin?

I've always sucked at understanding things related to pharmacokinetics, and this is no exception...

I appreciate any info, but err... try to make it organized .

I'm not sure if you're going to get an easy answer to this question. Here are a few things to consider:

-This review paper on amino acid transport systems found throughout the body (including the GI) shows how many different amino acid transport systems there actually are. The transporters are probably specific for chemically related groups of amino acids, i.e. zwitterionic species use one set; hydrophobic, another set, small hydrophilic, a third set; etc.
- The type of amino acids present in your diet changes the levels of expression of the relevant amino acid transporters on the intestinal mucosal cells. For example, if your diet provided abundant tyrosine but insufficient glycine, the intestinal cells would upregulate Gly-specific transporters and downregulate Tyr-specific transporters.

Perhaps also relevant:
- 30-40% of the dietary amino acids absorbed in the GI are used by the intestinal cells themselves as an energy source, and in the production of mucin (mucus), especially glycine, cysteine, and glutamate (of which 90% is used by the cells). These three amino acids might therefore have the highest specificity for GI cells, but the lowest rate of transport across the cells, and into the blood stream.

 

[Whitespy420]

The amino acids also compete for absorbtion upon entrance to the brain and crossing the BBB - oh shit, my link's dead. And you're asking about GI absorbtion. I'll come back later with some better info, I had done some research on supplementation with individual long chain amino acid vs protein supplementation a while ago (I take ALCAR for neuroprotective reasons, I guess to give myself some reassure that my drug use will have the least amount of impact), and its on another computer, I'll repost it once I got that one up and running.

 

[fastandbulbous]

I'm not sure, but I think the amino acids are absorbed via a facilitated diffusion process ie the carriers do not work against a concentration gradient, but are a passive process that 'helps along diffusion'; that's just as well due to their zwitterion nature and that they're generally least soluble at their isoelectric point (pH where neither the NH2 nor the COOH group is ionized). That would mean that to be in solution to allow normal diffusion, they need to be ionized & ionized compounds are not lipid soluble (therefore will not cross lipid region of cell membrane)

Ain't nature clever!

 

[raybeez]

Anyone know if peptides/polypeptides, i.e. semi-degraded proteins can be taken up by GI cells? It might be a way to get around problems with uptake of zwitterionic species. E.g. cells take up a 5-amino acid long peptide chain, and degrade it further intracellularly to yield the free amino acids that would be more difficult to take up in their native forms...

 

[Dondante]

This may or may not be helpful. There is one large neutral amino acid transporter shared by many amino acids (Phe, Tyr, Leu, Ile, Val, Trp, Met, His, L-DOPA) that is used for transport across the BBB. This results in competitive inhibition. These amino acids compete w/ each other for entry so abnormal elevation of one in the blood can reduce uptake of others.

Edit: just found this article

Intestinal protein digestion generates a huge variety and quantity of short chain peptides that are absorbed into intestinal epithelial cells by the PEPT1 transporter in the apical membrane of enterocytes. PEPT1 operates as an electrogenic proton/peptide symporter with the ability to transport essentially every possible di- and tripeptide. Transport is enantio-selective and involves a variable proton-to-substrate stoichiometry for uptake of neutral and mono- or polyvalently charged peptides. Neither free amino acids nor peptides containing four or more amino acids are accepted as substrates. The structural similarity of a variety of drugs with the basic structure of di- or tripeptides explains the transport of aminocephalosporins and aminopenicillins, selected angiotensin-converting inhibitors, and amino acid-conjugated nucleoside-based antiviral agents by PEPT1. The high transport capacity of PEPT1 allows fast and efficient intestinal uptake of the drugs but also of amino acid nitrogen even in states of impaired mucosal functions. Transcriptional and post-transcriptional regulation of PEPT1 occurs in response to alterations in the nutritional status and in disease states, suggesting a prime role of this transporter in amino acid absorption.

http://www.ncbi.nlm.nih.gov.libprox..._uids=14977407&query_hl=4&itool=pubmed_docsum

I just happened to be studying this right now ... according to my biochem book, oligopeptides are cleaved to free AAs and smaller peptides by aminopeptidase on the luminal surface of the intestine. Apparently AAs can be absorbed as tripeptides, but I believe they are pretty much all converted to individual AAs before reaching the portal vein. I haven't seen anything about competition for this carrier. I think most of the regulation of amino acid levels is internal via the urea cycle, and subsequent metabolism of the carbon skeletons (excess AAs are metabolized) ... not really sure about that though. Hope that helps a little.