The kinetic properties of hexokinases in African trypanosomes of the subgenus Trypanozoon match the blood glucose levels of mammal hosts.

Abstract

We hypothesize that the hexokinases of trypanosomes of the subgenus Trypanozoon match the blood glucose levels of hosts. We studied the kinetic properties of purified hexokinase in T. equiperdum (specific activity=302U/mg), and compare with other members of Trypanozoon. With ATP (Km=104.7μM) as phosphate donor, hexokinase catalyzes the phosphorylation of glucose (Km=24.9μM) and mannose (Km=8.8μM). With respect to glucose, mannose and inorganic pyrophosphate respectively are a competitive, and a mixed inhibitor of hexokinase. With respect to ATP, both are mixed inhibitors of this enzyme. In T. equiperdum, hexokinase shows a high affinity for glucose. Pleomorphism-transformation of trypanosomes from a multiplicative to a non-multiplicative form-results in a self-limited growth stabilizing glucose consumption. It delays the death of the host, thus prolonging its exposure to tsetse flies. When glucose levels descend, top-down regulation allows trypanosomes to survive through the expression of alternative metabolic pathways. It accelerates the death of the host, but helps trypanosome density to increase enough to ensure transmission without tsetse flies. Pleomorphism, and a hexokinase with a high affinity for glucose, are two main adaptive traits of T. b. brucei. The latter trait, and a strong top-down regulation, are two main adaptive traits of T. equiperdum. For trypanosomes living in glucose-rich blood, a hexokinase with a high affinity for glucose would unnecessarily harm hosts. This may explain why the human parasites, T. b. gambiense and T. b. rhodesiense, possess hexokinases with a low affinity for glucose.