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From: j.nobel.daggett@gmail.com (LDagget)
Newsgroups: talk.origins
Subject: Re: What is legitimate about the ID bait and switch scam at this
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Date: Tue, 17 Jun 2025 18:30:42 +0000
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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.