Muscle FBPase in a complex with muscle aldolase is insensitive to AMP inhibition

Abstract

Real-time interaction analysis, using the BIAcore biosensor, of rabbit muscle FBPase^aldolase complex revealed apparent binding constant [K Aapp ] values of about 4.4U U10 M31 . The stability of the complex was down-regulated by the glycolytic intermediates dihydroxyacetone phosphate and fructose 6-phosphate, and by the regulator of glycolysis and glyconeogenesis^fructose 2,6-bisphosphate. FBPase in a complex with aldolase was entirely insensitive to inhibition by physiological concentrations of AMP (I 0:5 was 1.35 mM) and the cooperativity of the inhibition was not observed. The existence of an FBPase^aldolase complex that is insensitive to AMP inhibition explains the possibility of glycogen synthesis from carbohydrate precursors in vertebrates' myocytes.

Crystal Structures of Human Muscle Fructose-1,6-Bisphosphatase: Novel Quaternary States, Enhanced AMP Affinity, and Allosteric Signal Transmission Pathway

“…Varying any of these residues would destroy this network and decrease its binding affinity for AMP. This is supported by kinetic results from the K20E (22 fold), T177M/Q179C (11 fold), and K20E/T177M/Q179C (26 fold) mutants of human muscle Fru-1,6-Pase showing their decreased sensitivity towards AMP [29]. In fact, the sensitivity of the triple mutant of hmFru-1,6-Pase to AMP is similar to that of human liver Fru-1,6-Pase.…”

“…In gluconeogenesis, as well as in glyconeogenesis, the substrate for muscle Fru-1,6-Pase is supplied by aldolase. Muscle aldolase strongly interacts with muscle Fru-1,6-Pase resulting in the formation of a heterologous Fru-1,6-Pase-aldolase complex, which is not sensitive to AMP inhibition [29].…”

Ubiquitous presence of gluconeogenic regulatory enzyme, fructose-1,6-bisphosphatase, within layers of rat retina

“…Thus, the provision of substrates for NADP reduction and/or glycogen synthesis from non-carbohydrates should cease in their presence. The only known factor desensitizing muscle FBPase to the action of its inhibitors is the muscle isozyme of aldolase, viz., aldolase A (Rakus et al 2003, 2004; Mamczur et al 2005). Studying the distribution of FBPase in the rat retina, we have found that the enzyme co-localizes with aldolase.…”

The regulation of the interaction between F-actin and muscle fructose 1,6-bisphosphatase

“…On the other hand, the synthesis of glycogen from carbohydrate precursors in skeletal muscle, in which FBPase is indispensable, has been observed [5][6][7]. Recently, we have shown that in skeletal muscle cells, FBPase participates in the formation of the triple aldolase-FBPase-␣-actinin complex on both sides of the Z-line [8], in which FBPase is entirely desensitized by aldolase to AMP inhibition [3,9].…”