Biology Reference
In-Depth Information
120
min
90
min
60
min
30
min
0
min
110
105
100
95
90
PPM
Figure 2
Typical course of
13
C NMR spectra of muscle glycogen in a representative
normal subject during the hyperglycemic-hyperinsulinemic clamp study.
The C-1 peak of glycogen appears at 100.4 ppm. (Reproduced from Shulman GI, Rothman DL,
Jue T, Stein P, DeFronzo RA, Shulman RG,
New Engl J Med
322:223-228, 1990 by permission
of Massachusetts Medical Society).
control coefficient these results showed that the flux was completely controlled
by glucose transporters and plasma glucose concentrations, the first step in the
pathway. The pathway of glycogen synthesis, in which the flux was controlled
by the concentration of the substrate, glucose, is an experimentally determined
example of supply control (Fell, 1997).
At this point the summation theory of flux control coefficients showed that
all the enzymes in the pathway following the first step had negligible flux con-
trol. This means that glycogen synthase (GSase), an allosteric enzyme under
phosphorylation control, is not contributing significantly to the control of the
flux of glycogen synthesis. As the velocity of GSase is elaborately controlled
by numerous second messengers, hormones, activating control pathways that in
turn activate kinases and/or phosphatases which regulate the enzyme's activity,
this result raises the question as to the function of these regulating pathways.
MCA answers this question theoretically, because a top-down analysis of the
pathway would show that GSase is expected to be exercising metabolite control.
Experimental support came from the third
in vivo
measurement made possible
by MRS. The
31
P spectrum, of a nucleus that is 100% abundant, was measured
