Phospholipids, glucose-6-phosphatase

Zl. Zakim, D., Regulation of microsomal enzymes by phospholipids. I. The effect of phospholipases and phospholipids on glucose 6-phosphatase. J. Biol. Chem. 245, 4953-4961 (1970). 

In 1954, Beaufay and de Duve (27) first suggested a relationship between microsomal phospholipid and glucose-6-phosphatase. They observed a loss of enzymic activity from phospholipid-rich microsomal preparations concomitant with extraction with such organic solvents as butanol or treatment with lecithinase. Various studies were carried out to demonstrate that the latter effect was not produced through inhibition of enzymic activity by accumulated products of the hydrolysis of phospholipids. On the basis of their observations that deoxycholate treatment labilized microsomes to phospholipase action, they concluded that . . . the detergent did not exert its primary effect on the dissociation of phospholipids from microsomal protein, but that it probably disrupted... 

An excellent review of this earlier work on the involvement of phospholipids with glucose-6-phosphatase is given in a doctoral dissertation by Ganoza (81). 

As might reasonably be expected on the basis of the intimate relationships between glucose-6-phosphatase and phospholipids discussed above,... 

In plants, inositol is biosynthesized from glucose 1-phosphate via inosose 1-phosphate, which is reduced into ID-inositol 3-phosphate (INOl pathway). After dephosphorylation by inositol phosphate monophosphatase, myo-inositol is fed into biosynthesis of inositol phospholipids via a Kennedy-like sequence. In mammalian organisms, inositol is acquired from the diet and is also biosynthesized via INOl. The latter pathway, rather than the inositol phosphate phosphatase, seems to be a more promising target of antipsychotic drugs (17, 18) (see Fig. 2). 

Intragastric dosing with capsaicin (50 mg g 1 day ) for 60 days caused reduced body weight gains and reductions in plasma urea nitrogen, glucose, phospholipids, triglyceride, transaminase and alkaline phosphatase (Monsereenusom, 1983). 

Membrane enzymes enzymes present on the surfaces or integrated into the phospholipid bilayer of the many different types of Biomembranes (see), e.g. glucose 6-phosphatase of the endoplasmic reticulum, galactosyl transferase of the Golgi apparatus, oli-gomycin-sensitive ATPase of the inner mitochondrial membrane, monoamine oxidase and rotenone-insen-sitive NADH-cytochrome c-reductase of the outer mitochondrial membrane, and the sodium-independent ATPase and 5 -nueleotidase of the cell membrane. Very many reactions occur on membranes, and M.e. play a central part in cell metabolism. M.e. are useful as markers in the isolation and identifica-... 

In conclusion, the morphological identification of each cell fraction should be completed by its biochemical characterization. This should include the determination of basic compounds (nitrogen, nucleic acids, and phospholipids) and the assay of specific reference enzymes (cytochrome oxidase, glucose-6-phosphatase, and acid phosphatase). 

Membrane lipids may be essential for the actions of certain membrane enzymes and may have more than structural significance. For example, ATPase activity, microsomal glucose-6-phosphatase, electron transfer enzyme chain in mitochondria (Green and Perdue, 1966), and a large number of microsomal enzymes appear to require phospholipids for their activity. 

That phospholipid may be an essential part of glucose-6-phosphatase is the conclusion derived from the work of several authors who have studied the effects of phospholipases A and C (Duttera et al., 1968 Fleisher et al., 1962) and who have added phospholipid to lipid-free microsomal glucose-6-phosphatase (Kashnitz and Mittermayer, 1969). 

In the case of 5 -nucleotidase as for glucose-6-phosphatase, the enzyme is inseparably bound with phospholipid and the use of detergents such as deoxycholate merely serve to keep the dissociated enzyme and phospholipid units in a state of homogeneous dispersion. Evidence for this is based on the fact that the subsequent removal of detergent by dialysis resulted in the appearance of membranous vesicles as seen under the electron microscope (Song et al., 1967). 

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