Experimental evidence for a zero-order ultrasensitivity in a simple substrate cycle.
It was shown [Goldbeter & Koshland (1981), Proc. Natl. Acad. Sci. USA, 78, 6840-6844] that amplified sensitivity may arise in reversible covalent modification systems, when the converter enzymes operate in their zero-order region. We show that "zero-order ultrasensitivity" may also occur in simple substrate cycles. The experimental study deals with the Formate/Lactic dehydrogenases model cycle, interconverting the reduced and oxidized forms of NAD. For NAD(H) concentrations high enough (with respect to the enzyme KM's), abrupt changes in the steady-state substrate concentrations may result from small variations in the ratio of maximal enzyme activities. The amplification factors are measured. Implications in metabolic regulation are also taken up.
Laboratoire de Technologie Enzymatique, U.A. No 523 du C.N.R.S., Université de Compiègne, France.
A
A
Cimino
J F
JF
Hervagault
D000445:Aldehyde Oxidoreductases; D005560:Formate Dehydrogenases; D007700:Kinetics; D007770:L-Lactate Dehydrogenase; D009243:NAD / Q000378:metabolism
D009243:NAD; D007770:L-Lactate Dehydrogenase; D005560:Formate Dehydrogenases; D000445:Aldehyde Oxidoreductases