Evolution of Two Cellular Shuttle Systems
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Transcript of Evolution of Two Cellular Shuttle Systems
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The Evolution of two cellular Shuttle Systems.
Peter Gauthier
Since chemical reactions tend to equilibrium, it seems reasonable to
assume that the driving evolutionary force of catabolic metabolism may
have been the Free Energy Change of chemical reactions, as they proceed to
equilibrium. The useful energy is preserved as bond energy and the rest is
lost as heat. For this reason there seems to be a selective advantage for cells
to use catabolic pathways that yield the most energy. If this is true then
those catabolic reactions which yield the most energy would tend to prevail,
and in this way the most energy available from molecules would be
harnessed for cell use.
During aerobic glycolysis, the coenzyme NAD+ is regenerated fromits reduced form, NADH, by shuttle systems that move from the cytoplasm
into the mitochondria. Since NAD+ is present in catalytic amounts, and does
not enter the mitochondria to be oxidized, a shuttle system between the
cytoplasm and the mitochondria is essential. Two examples of molecular
systems that shuttle between the cytoplasm and the mitochondria are
DHAP/AGP and OAA/MA systems (1).
Of the two systems, more energy is derived from the OA/MA system
(3 ATP molecules ) than from the DHAP/AGP system (2 ATP molecules).
This disparity is due to the different intermediates of the electron transportchain that each reduces (2).
Now if selection of one of these shuttle systems were based solely on
the available energy that can be derived, then one could assume that the
OAA/MA system would be selected exclusively. But in fact, some tissues
utilize the DHAP/AGP system as a shuttle in spite of the fact that less
energy is realized from this pathway.
The cell can realize 38 ATP molecules from the complete oxidation of
a glucose molecule using the OAA/MA system, whereas only 36 molecules
of ATP are produced using the DHAP/AGP system.
If these systems were being selected strictly on the basis of theavailable energy, then the OAA/MA system would always be the system of
choice. But in some tissue the DHAP/AGP system is used so there must be
some other selective advantage for the cell to use this system other than the
energy that can be obtained. Perhaps the availability of the shuttle
intermediates plays a determining role in the matter.
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In this light, an explanation for the use of the DHAP/AGP system is
the proximity of DHAP to the key reaction of glycolysis in which NADH is
the product, namely the oxidation of PGAL to 3-PGA. Since DHAP is in
equilibrium with PGAL, as PGAL is pulled off the equilibrium and oxidized
to 3-PGA, there is a DHAP molecule available to act as a shuttle for each
NADH that is produced in this reaction. So in this case availability may be
more important to the selective process than the energetic imperative.
The overriding determinant in this case may simply be whatever the
traffic will bear and this may guide the selective process resulting in a
system that delivers less energy simply because an easier route was
available.
It seems reasonable to assume that in the evolution of catabolic
pathways, those reactions in which the most available energy could be
harnessed for cell use would be selected. But since that isnt true in theDHAP/AGP case, and of the two shuttle systems which perform the same
function the one resulting in less energy is used in some tissue, it would
seem another principle is being tested here.
It seems that natures repertoire is only as large as it has to be to meet
the demands, and it doesnt necessarily result in a system that extracts the
most chemical energy; the lesser of the two systems, energetically, has also
survived. There is no need to go beyond this, so nature doesnt strive for
perfection, i.e. to select the system from which the most energy is derived.
The process of natural selection doesnt necessarily result in the best system
energetically, but in regard the DHAP/AGP system, simply the more
convenient.
1. Shuttle reactions in the cytoplasm.
(a) DHAP + NADH ------> AGP + NAD+
(b) OA + NADH ------> MA + NAD+
2. Shuttle reactions in the mitochondria showing ATP yield.
(a) AGP + FAD -----> DHAP + FADH2 + 2 ATP
(b) MA + NAD+ ----->OA + NADH + 3 ATP
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Note: (a). The OA/MA system involves other intermediates (Glu & Asp),
but the net effect is that MA diffuses into the mitochondria and OA is
regenerated in the cytoplasm via the amino acids, Glu and Asp.
(b). The ATP molecules generated may be less for each system but
the relative ratio of the systems, OA/MA / DHAP/AGP is about the same sothe principles still stand.
Glossary:DHAP: Dihydroxyacetone phosphate
AGP: Alpha glycerophosphate
OAA: Oxaloacetic acid
MA: Malic acid
PGAL: Phosphoglyceraldehyde
3-PGA 3-Phosphoglycerate
References:
Origins. Speculations about the Spontaneous Generation of the first Biotic
Structure, Peter Gauthier. BIOS Vol. 65 No. 4 (1995)
Lehninger:Principles of Biochemistry. Worth Publishing 1982
Garrett & Grisham:Biochemistry. 2nd Ed. Saunders Publishing 1999
Peter Gauthier
1992