Subject: TCA cycle = beta oxidation?

From: [email-masked] (Morgan J Ryan -- Neil Patterson Publishers)
Date: 3 Nov 1993 02:57:01 GMT

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 / [email-masked]

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From: [email-masked]
Date: Fri, 5 Nov 1993 07:49:15 GMT

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

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From: [email-masked] (Harald Osmundsen)
Date: 5 Nov 1993 14:46:36 GMT

> Morgan Ryan / [email-masked]

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