Liver fructose-1,6-diphosphatase

Although gluconeogenesis is generally considered to be confined to liver and kidney, evidence for the presence of a specific FDPase in muscle has been reported from a number of laboratories. Significant levels of activity are to be found in skeletal muscle of a wide variety of vertebrates including mammals, birds, and amphibia (71, 72). The levels of activity in white muscle were reported to be similar to those found in liver and kidney, but the enzyme was not detected in heart muscle or in smooth muscle of several species tested. Fructose diphosphatase in crude muscle extracts has been reported to be stimulated by EDTA (72). 

Pll. Pontremoli, S., Luppis, B., Wood, W. A., Traniello, S., and Horecker, B. L., Fructose diphosphatase from rabbit liver. II. Changes in catalytic properties Induced by dinitrofluorobenzene. J. Biol. Chem. 240, 3464-3468 (1965). 

Hulsman, W.C. and Fernandes, J. (1971), A child with lactic acidaemia and fructose diphosphatase deficiency in the liver. Pediatrics, 5,633. 

In order to give useful information about an enzyme, a conformationally restricted active-site-directed analog inhibitor need not bind to the enzyme irreversibly. In a study of the enzyme fructose 1,6-diphosphatase from rabbit liver, Benkovic et al, have investigated the question of the reactive form of the fructose 1,6-diphosphate in the enzymatic process (104,105). Three likely forms are shown in structures 50, 51 and 52. 

Fructose 1,6-diphosphatase can be isolated from many mammalian systems, including rabbit liver,360 muscle,361,362 rabbit kidney,363 swine... 

D-Fructose 1,6-diphosphatases from rabbit liver and muscle are similar in their cation-requirement profile, molecular weight, substrate affinity, and substrate inhibition, but have different amino acid compositions, and the muscle enzyme does not cross-react with antibody to the purified liver-enzyme.361,364 The muscle enzyme is more sensitive to AMP than the enzyme from liver or kidney.385... 

Taketa and coworkers398 reported that ATP and ADP inhibit rabbit-liver D-fructose 1,6-diphosphatase, and that the inhibition results from a conversion of the enzyme into a conformer having low activity. Skeletal-muscle enzyme is inhibited by ADP. 

Regulation of liver D-fructose 1,6-diphosphatase could involve modification of the sulfhydryl group of the enzyme.397 Cystamine (2,2 -dithiobisethylamine) or homocysteine undergoes a disulfide exchange-reaction with two reactive cysteine residues. This exchange leads to a four-fold increase in catalytic activity.405 Other sulfhydryl reagents, such as l-fluoro-2,4-dinitrobenzene (FDNB), p-mercuri-benzoate (PMB), and 2-iodoacetamide, also activate liver D-fructose... 

Fig. 79. Activity of fructose-1,6-diphosphatase in the rat liver after birth (Ballard and Oliver, 1962).

It was also beheved that the gluconeogenic machinery, including four critical enzymes pyruvate carboxylase, PEP carboxykinase, fructose-1,6-diphosphatase, and glucose-6-phosphatase could be fuUy expressed exclusively in the liver and in the kidney. Specifically, with the exception of hepatocytes and renal cortical cells, it was considered impossible that any glucose synthesized de novo or released Irom local glycogen stores could be released in the systemic circulation, because of the absence of gJucose-6-phosphatase. 

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