I will break your question into some possible sub-questions: 1) Why
are ketone bodies rather than acetyl-CoA used as the transporter? 2)
Why are ketone bodies (at least oxaloacetate and hydroxybutyrate) used
in preference to acetate? 3) Any other considerations?
1) Why ketone bodies rather than acetyl-CoA? One reason acetyl-CoA
might not be used is that there is probably not enough CoA (it being a
derivative of the vitamin, pantothenic acid, and, as such, not being
as abundant in the body in as the molecules being burned as fuel).
Inside the mitochondrion, CoA handles multiple fuel molecules, but
successively. For possible transport in the bloodstream, you would
likely need much more CoA, enough to equal the concentration of all
the "acetate" groups being transported in the bloodstream.
2) Why ketone bodies rather than acetate? Using ketone bodies is more
energy efficient than using acetate as the transport molecule. If two
acetates were transported directly in the bloodstream, two high energy
bonds (in the two starting acetyl-CoA molecules) would have to be
broken, then resynthesized again before use in peripheral tissues. If
oxaloacetate is used instead of two acetates, there is a net need for
only one high energy bond to be used in getting back to two acetyl-CoA
molecules (see following).
For transport as acetate:
2 high-energy bonds broken in converting 2 acetyl-CoA to 2 acetates;
both bonds need to be resynthesized before the acetate can be used for
energy again.
For transport as oxaloacetate:
2 high-energy bonds broken in converting 2 acety-CoA to 1 oxaloacetate
(BUT the energy of one of those bonds is stored in the newly
synthesized "aceto" - "acetate" bond in oxaloacetate - note that the
conversion from two acetyl-CoA to one oxaloacetyl-CoA is readily
reversible without the input of energy). This reversibility lets a
cell in peripheral tissue convert oxaloacetyl-CoA to two acetyl-CoA
molecules without the need for additional energy; the only energy
needed in the peripheral cell is the one high-energy bond created in
converting oxaloacetate to oxaloacetyl-CoA.
Net result: For transport of 2 acetyl-CoA molecules as oxaloacetate,
there is a net need of only one high energy bond to resynthesize the
two acetyl-CoA molecules in a peripheral tissue. The energy in one of
the two starting acetyl-CoA molecules is not lost as it would have
been if two acetyl-CoA molecules were simply cleaved to two acetate
molecules.
3) There could additional considerations. For instance, (though
somewhat off from your question) ketone bodies are water soluble and
don't need blood proteins to help in transport - unlike fatty acids,
whose transport is aided by blood proteins. Not needing proteins for
transport is an advantage under starvation conditions, where ketone
body transport becomes more prominent. |
