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.