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From: DB Cates <cates_db@hotmail.com>
Newsgroups: talk.origins
Subject: Re: What is legitimate about the ID bait and switch scam at this
 time?
Date: Tue, 17 Jun 2025 18:54:14 -0500
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On 2025-06-17 1:30 p.m., LDagget wrote:
> On Tue, 17 Jun 2025 17:21:50 +0000, RonO wrote:
> 
>> On 6/17/2025 10:07 AM, LDagget wrote:
>>> On Mon, 16 Jun 2025 23:23:28 +0000, RonO wrote:
>>>
>   snippage
> 
>> What I have always gone by was that when D and L charged tRNAs were in
>> the mix, translation still proceeded, but more slowly and L amino acids
>> were still used in making the peptide.  I did not recall any type of
>> controversy involved, but the paper that I linked to noted that it has
>> never been understood why the D amino acids were not incorporated.
> 
> 
> As with so much biochemistry, it's complicated when you get into the
> weeds. Then again, from some perspectives, it's rather simple.
> 
> The perspective I was weened on is one of kinetics. An aminoacyle
> tRNA synthetase is an enzyme that, in our modern world, catalyzes
> the joining of an L-amino acid of the right sort, to a tRNA of
> the right sort. For example, Metionine aminoacyl tRNA synthetase
> catalyzes the reaction
> 
> L-Methionine  + tRNA^(Met)(CAU) ==> Met-tRNA^Met(CAU)
> 
> The ^ indicates the (Met) should be Met written as superscript.
> (CAU) identifies the anticodon of the tRNA.
> 
> That's a reasonable description which is a good first order
> understanding of what happens. Then the fun begins. There is a variant
> of the amino acids Leucine and Isoleucine called norleucine. These are
> all amino acids whose R group is C4H9
> 
> So for the generic amino acid H2 - N - CH(R) - COOH we roll through
> different substitutions for R.
> 
> Leucine R group is  -CH(CH3)-CH2-CH3. It branches early.
> 
> 
> Isoleucine R group is  -CH2-C(CH3)2. It branches late.
> 
> Norleucine R groupis -CH2-CH2-CH2-CH3   It does not branch.
> 
> Note: Methionine has the R group CH2-CH2-S-CH3
> 
> It "looks" just like Norleucine if you swap out the last CH2 for an S.
> 
> And gosh darn, but Met tRNA synthetase also catalyzes the reaction
> 
> L-Norleucine  + tRNA^(Met)(CAU) ==> Nle-tRNA^Met(CAU)
> 
> The damned thing apparently didn't read the textbook or attend
> the lectures. Our understanding is that this happens because the
> aminoacyl synthetase discriminates according to the shape of the
> amino acid but methionine and norleucine have very similar shapes.
> 
> The biotech industry has witnessed significant levels of norleu
> incorporation in place of met in fermentation products. It's one of
> those things that repeats in cycles because a new generation comes
> along who read the textbooks and attended the lectures but didn't listen
> to old geezers who work for a living.
> 
> It's always happening at some level. A proper biochemist will think of
> it this way.
> 
> The rate at which it happens will depend upon the concentration of L-Met
> and L-Nle inside the cell synthesizing the protein. If the cells are
> being
> fed cheap Purina Cell Chow that has relatively high concentrations of
> non
> standard amino acids like Norleucine, it will happen more often. The
> enzyme
> Met aminoacyl transferase may even have a 5 or 10 fold preference for
> Met over Nle, but as synthesis progresses, and the concentration of Met
> in solution is reduced by incorporation into proteins, the ration of
> Nle to Met in the cell will increase. Other metabolic pathways will be
> at work to detect and synthesize more of amino acids whose
> concentrations
> dip, and some salvage pathways will consume other amino acids to make
> more Methionine, including consuming Norleucine, but not
> instantaneously.
> 
> Not to belabor it (too late, I know) but similar competition exists
> with every amino acid tRNA aminoacyl tRNA transferase.
> 
> The textbook reaction will be 100 fold, or 1000 fold faster for the
> "right" reaction for equal competing concentration. This will be true
> for L vs D forms of the same amino acid, or 'similar' amino acids. The
> specifics of the relative preferences vary.
> 
> But here the punchline. It's always a competition. There are always side
> reactions. Enzymes don't read textbooks or attend lectures. They don't
> know a CORRECT reaction from an INCORRECT reaction.
> 
> It's the same for DNA synthesis and so mutations happen.
> 
> If anyone read this far, you're entitled to tell me to shut up.
> Apologies for being so pedantic.
> 
I have been reading this thread with great interest and near zero 
understanding. But I enjoy that it illustrates an understanding that I 
was late to appreciate. That biology is *really* messy and the stories 
we are usually told are greatly simplified and 'prettied up', leaving 
out the true nature of what is actually happening. So, thank you both.

-- 
--
Don Cates ("he's a cunning rascal" PN)