Evolution of glycolysis

The allosteric regulation of pyruvate kinase

“…2A The reaction is catalysed by pyruvate kinase (PK), which requires for its activity both monovalent and divalent cations [1,2]. PK is a typical allosteric enzyme [3], and plays a major role in the control of the metabolic flux from fructose-l,6-bisphosphate (FBP) to pyruvate, in the second section of glycolysis (see Fig. 1).…”

“…FBP is also the activator of nearly all characterised eukaryotic PK molecules, even though in trypanosomes the enzyme activator is fructose-2,6-bisphosphate [4]. More sophisticated is the control in mammals, where four PK isoenzymes are expressed in a tissue-specific manner [3,5]: M1 PK present mostly in the skeletal muscle; M2 PK in many tissues such as kidney, intestine, lung fibroblasts, testis, and stomach; L PK mostly in the liver; R PK exclusively in the red blood cells. The FBPdependent M1 and R isoenzymes share allosteric properties similar to those of the other eukaryotic PK molecules, Fig.…”

“…Glycolysis; Metabolism regulation; X-ray crystallography; Pyruvate kinase whereas the L PK is additionally controlled by phosphorylation on a N-terminal Ser residue which causes a decrease in the affinity for the PEP and FBP activators [3]. More unusual is the muscle M1 protein [6] which is the only known PK displaying hyperbolic kinetics and no allosteric control.…”

Evolution of glucose utilization: Glucokinase and glucokinase regulator protein

“…Cárdenas et al (1998) unfortunately used the UPGMA (unweighted pair-group method with arithmetic mean (Sokal and Michener, 1958)) method to calculate a tree for mammalian hexokinases, using protein sequences distances calculated by FothergillGilmore and Michels (1993). As acknowledged by the authors (Cárdenas et al, 1998), UPGMA assumes that the sequences have evolved at the same rate, but it was already clear from the distance data (Fothergill-Gilmore and Michels, 1993) that the N-terminal domains of hexokinases evolve more rapidly than the C-terminal domains. The UPGMA distance tree generated by Cárdenas et al (1998), unsurprisingly, yielded an unexpected tree where the two halves of hexokinase III have different origins.…”

“…Only the C-terminal kinase domains of hexokinase I and II have been demonstrated to have kinase activity (White and Wilson, 1989;Tsai and Wilson, 1997). Loss of the hexokinase activity may account for the more rapid evolution of the N-terminal domains of the hexokinase I and III protein sequences, and thus explain, at least in part, the observed greater divergence in sequence of the N-terminal, compared to C-terminal, domains of the 100kD hexokinases (Fothergill-Gilmore and Michels, 1993;Cárdenas et al, 1998). The more rapid evolution of the N-terminal regions of hexokinase I and III suggests that a smaller portion of these sequences are constrained by evolution, however, the observation that these sequence are retained in hexokinases from diverse vertebrates suggest that these sequences likely still have functional roles.…”