🚀 go-pugleaf

I'm not a "pretty impressive biochemist" so I'd appreciate hearing the
criticisms *before* I try and suggest anything...:)

But anyway, my view is that if you are given a starting material and a
desired product then there are only so many ways to achieve the specific
conversion.  There aren't too many ways to oxidize -CH2-CH2- to -C(O)-CH2-.
So there *may* be structural homology between the FA and TCA enzymes due
to common ancestry (divergent evolution), but there *may not* (i.e. 
convergent evolution of enzymes to do similar reactions in similar ways).

    That said, FAD-using and NAD-using enzymes would be expected to share
structural similarity in the cofactor-binding portions of the enzymes; the
CoA binding in the FA metabolic enzymes obviously is unnecessary in the
TCA enzymes however.  So we would expect similarities *and* differences, 
and this is actually what we find when comparing any two enzymes that 
perform similar but non-identical reactions.

   As to *why* always FAD and NAD, this seems to be a case of divergent 
evolution.  (Convergent evolution has happened for other kinds of enzymes.)

   As to *why* CH2-CH2 ----> C(O)-CH2?  I would guess that this reliance on
acetyl group formation (and acetyl CoA) allows a "common currency" of 
metabolism so that the TCA and the FA metabolic pathways ultimately 
respond to each other.  This is useful since fat is used as an energy
storage --- you stockpile it when you can and don't use it until you have to.

That's my attempt.  Seriously I am curious as to what objections have been
raised and what stances they were raised against!!

Ed Young

In article <2b76lt$rs8@inxs.concert.net>, morgan@rock.concert.net (Morgan J Ryan -- Neil Patterson Publishers) says:
>
>        Hi. Your ingenuity please.
>        Three sequential reactions of fatty acid oxidation are chemically
>identical to three reactions of the citric acid cycle. What is the
>explanation for this textbook chestnut? Is there some chemical or
>structural biological logic?
>        The reactions are fatty acyl CoA to 3-ketoacyl CoA and succinate
>to oxaloacetate. Basically that's:
>        beta oxidation                  citric acid cyc
>R--CH2--CH2--C(O)--COA ->       COO--CH2--CH2--COO 
>R--CH==CH--C(O)--CoA ->         COO--CH==CH--COO
>R--CHOH--CH2--C(O)--CoA ->      COO--CHOH--CH2--COO
>R--C(O)--CH2--C(O)--CoA         COO--C(O)--CH2--CO
>        I've heard some pretty impressive biochemists mock each other's
>ideas about why this sequence is repeated. Is there some subterranean
>chemical logic? I don't know if there is any structural congruity among
>the enzymes of the parallel reactions.Worth a look, I suppose, if there
>isn't a more obvious explanation.
>        Ideas?
> Morgan Ryan / morgan@rock.concert.net

It is, in my view, the chemical approache nature haave chose to use
 in order to oxidise a saturated alifatic carbon atom to a carbonyl-carbon atom.
In both succinate and a fatty acid it is a methylene-carbon atom which is oxidized to
a carbonyl-carbon atom. 

To what extent there is structural similarity between the enzymes - I do not know.
The coenzymes used are the same, so the ossibility is obviously there.


                                   Harald Osmundsen