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There are some natural peptides made of D-amino acids, rather than the L-amino acids normally found in nature. It is now possible to chemically synthesize artificial proteins made of D-amino acids.

If such proteins were ingested by individuals, how would they be metabolized and what consequences would they have?

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  • $\begingroup$ Please read the help on what questions are acceptable on Biology before posting: "You should only ask practical, answerable questions based on actual problems that you face. " $\endgroup$
    – David
    Commented May 10, 2018 at 12:29
  • $\begingroup$ I believe my question meets those guidelines. To follow on from the statement you quoted, "Chatty, open-ended questions diminish the usefulness of our site and push other questions off the front page.", and that is not the sort of question that I'm asking. I'm asking what the scientific understanding of what the effects of ingesting biological material composed of opposite-chirality amino acids would be. Since the properties of those chemicals are (presumably) well understood, the effects of eating said organic matter should be answerable. $\endgroup$
    – nick012000
    Commented May 10, 2018 at 12:39
  • $\begingroup$ Questions about alien planets are not on topic here. Also questions to which you have applied no effort yourself, assuming that you are a 'student' of biology. If you want to ask this question you need to think about the biochemistry involved. For example you could ask "Do the digestive proteases (trypsin, chymotrypsin, pepsin hydrolyse peptides made up of D-amino acids) and on from there to the next stage in digestion, assuming they do. Until you reformulate your question in such terms I hold by my opinion. $\endgroup$
    – David
    Commented May 10, 2018 at 14:45
  • $\begingroup$ I'm a computer programmer, I don't know anything about biology past high-school tier other than random bits of trivia. It's not my expertise; that's why I'm asking a question. If I already knew the answer I wouldn't have to ask, would I? Asking questions so that people who are experts in that field can answer them is literally the entire purpose of Stack Exchange. $\endgroup$
    – nick012000
    Commented May 10, 2018 at 14:49
  • $\begingroup$ I'm sorry Nick, but the first line of the Tour states "Biology Stack Exchange is a question and answer site for biology researchers, academics, and students." If I went onto Stack Overflow (as I do sometimes) and asked what a "for" loop was I wouldn't last two minutes. Indeed, if I have asked far more sophisticated questions that people regarded as too basic. And the problem of asking on a specialist SE is that you get specilized answers, that you likely wouldn't understand, or at least wouldn't be able to assess for correctness. (There's no code to run to check if it works for you.) $\endgroup$
    – David
    Commented May 10, 2018 at 15:01

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One aspect of the basic biochemistry needed to approach this question is the fact that the enzymes that catalyse cellular reactions show various levels of specificity towards their substrates (reactants), including stereo-specificity. This is illustrated below (an ill-favoured thing, but mine own). The first example shows that the specificity of proteases may depend on the general chemical or physical nature of the substrate. The second shows the how stereospecificity works.

Specificity of enzymes towards their substrates

The enzymes that are relevant here are proteases, which are responsible for breaking down proteins to their constituent amino acids, which are then absorbed by the gut, and then the enzymes that would normally catabolize (break down) or metabolize (convert to other compounds) those amino acids. It is well known that the specificity of the enzymes is such that, even if the proteins were broken down to D-amino acids, these could not be used for protein synthesis.

I am not an expert in this area (‘for’ loops are more my sort of thing) but I found some pertinent references in a recent paper on D-amino acid analogues of peptides. To quote from the introduction to that paper:

A useful consequence of this is that (D)-proteins are highly resistant to degradation and have low immunogenicity (7). The fundamental change in backbone–side-chain connectivity and geometry means they are not recognized as proteins by many (L)-proteins—including proteases. Consequently, (D)-proteins are reported to have greatly increased gut, blood plasma, and intracellular half-lives (8). Better cell penetration has also been reported in some cases (9, 10).

The references are:

  1. Uppalapati M, et al. (2016) A potent D-protein antagonist of VEGF-A is nonimmunogenic, metabolically stable, and longer-circulating in vivo. ACS Chem Biol 11:1058–1065.
  2. Rabideau AE, Pentelute BL (2015) A D-amino acid at the N-terminus of a protein abrogates its degradation by the N-end rule pathway. ACS Cent Sci 1:423–430.
  3. Nickl CK, et al. (2010) (D)-Amino acid analogues of DT-2 as highly selective and superior inhibitors of cGMP-dependent protein kinase Ialpha. Biochim Biophys Acta 1804:524–532.
  4. Brugidou J, Legrand C, Méry J, Rabié A (1995) The retro-inverso form of a homeobox-derived short peptide is rapidly internalised by cultured neurones: A new basis for an efficient intracellular delivery system. Biochem Biophys Res Commun 214:685–693.

So it would appear that the D-amino acid proteins are less likely to be metabolized and thus would be less likely to be useful as food. I do not understand why they would have low immunogenicity, but if this is the case it seems unlikely that they would cause allergic reactions.

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  • $\begingroup$ Could you please add an explanation about why L-amino acid could not be used to artificially synthetize proteins? $\endgroup$
    – totalMongot
    Commented Jul 25, 2023 at 19:38
  • $\begingroup$ @totalMongot — Of course they can, but that is not the question. $\endgroup$
    – David
    Commented Jul 27, 2023 at 9:45
  • $\begingroup$ Yes that's not the question, but I asked because the OP said that in his question: "There are some natural peptides made of D-amino acids, rather than the L-amino acids normally found in nature. It is now possible to chemically synthesize artificial proteins made of D-amino acids." $\endgroup$
    – totalMongot
    Commented Jul 27, 2023 at 10:16
  • $\begingroup$ @totalMongot I think you misinterpret what the poster wrote — certainly the state of chemical synthesis of peptides from amino acids. This was first achieved at the beginning of the 20th century, led to the synthesis of peptide hormones by the 1950s, and was made much more efficient by the introduction of the solid support methodology for which Merrifield received the Nobel prize in 1984. My mailbox is full of offers from companies that do this. Naturally L-amino acids were used, but D-amino acids will react similarly. That’s the point of needing to explain enzyme specificity towards L. $\endgroup$
    – David
    Commented Jul 28, 2023 at 16:20

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