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The gangliosides from the lymph nodes and blood sera of normal and T-lymphomic baboons were studied. In lymph nodes the major gangliosides were identified as GM3 and GD3, those in blood sera--as GM3, GM1 and GD3. Gangliosides GM3 and GD3 contained N-acetyl as well as N-glycoloyl neuraminic acids. In gangliosides isolated from lymph nodes and blood sera of T-lymphomic baboons the levels of N-glycoloyl neuraminic acid markedly exceeded that in normal tissues. In tumour lymph nodes the GM3/GD3 ratio was shifted towards GD3.

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Gangliosides of human gastric and mammary tumours and of homologous normal tissues were studied by using biochemical methods and specific antisera. It was found that in most cases GM3, GD3 and GM1 are predominant gangliosides, whereas several polar components are minor ones. A comparison of the relative amount of ganglioside fractions revealed that in gastric tumours the per cent content of polar compounds is higher than in intact tissue; however, the absolute content of all gangliosides is markedly increased. A comparative study of the composition of mammary tumour and normal tissue gangliosides demonstrated two types of changes: i) the absolute content of all gangliosides in tumour tissue was increased and, ii) the increase in the content of total gangliosides was paralleled with the appearance of a new fraction (presumably GM4), the decrease of the GD3 content and the disappearance of polar gangliosides. A possible mechanism of this effect is discussed.

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The glycosphingolipids of human lymphoma MOLT-4 cells were studied, using biochemical methods and specific antisera to gangliosides. The major neutral glycosphingolipids were found to be glucosyl- and lactosyl ceramides. GM3, GM2, GM1 and GD1a were identified as ganglioside components.

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The effects of the phospholipid composition of rat liver microsomes on the differential binding spectra of cytochrome P-450 with type I and II substrates (hexobarbital and aniline) were studied. Lysophosphatidylcholine was found to decrease the binding of both type substrates. These changes were reversible, and the spectra were restored by exchanging the microsomal lysophosphatidylcholine for unsaturated phosphatidylcholines, but not with dipalmitoylglycerophosphocholine, sphingomyelin, phosphatidylserine, and phosphatidylethanolamine. Phosphatidylinositol favoured only the binding of type II substrates. The data obtained indicate that the substrate binding capacity of cytochrome P-450 depends specifically on the "boundary" lipids, but not on the bulk lipids of the microsomal membrane.

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The effects of exogenous glycosphingolipids on the cytotoxic activity of natural killer (NK) cells and on the sensitivity of target cells were studied. Incubation of splenocytes with gangliosides of the hemato-series (GM3 and GD3) or with their precursor, LacCer, decreases the cytotoxic NK-activity, whereas some other acidic and neutral glycolipids do not possess such capability. On the other hand, incubation of target (YAC lymphoma) cells with glycolipids of the hemato-series increases the sensitivity of these cells to the cytotoxic action of NK-cells. A comparison of the ganglioside profiles of two YAC call lines differing in their NK-sensitivity revealed the presence of a GD3-like component in the highly sensitive cell line and the absence of this ganglioside in low sensitive target cells. It is assumed that gangliosides of the hemato-series are components of the acceptor complex on the surface of the target cells and that shedding of these gangliosides (especially, of GD3) by tumour cells is one possible mechanism of NK-activity suppression during malignant growth.

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Modification of membrane lipid composition by lipid exchange proteins was used to study the lipid dependence of cytochrome P-450 activity in rat liver microsomes. The introduction of exogenous lysophosphatidylcholine into microsomal membranes decreased the capacity of cytochrome P-450 to demethylate dimethylaniline and dimethylaminoantipyrine and to hydroxylate aniline. A subsequent introduction of phosphatidylcholine resulted in an almost complete reactivation of the enzyme.

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The incorporation of lysophosphatidylcholine into biological membranes and its effect on some membrane-bound enzymes of mitochondria and microsomes from rat liver and hepatoma were studied. It was shown that in the presence of lipid-exchange proteins of the liver a far greater amount of lysophosphatidylcholine is incorporated into the membranes than in the-iv absence. The increase of the lysophosphatidylcholine content in the membranes has no effect on the activity of mitochondrial monoamine oxidase, inhibits the activity of microsomal cytochrome P-450 and activates glucose-6-phosphatase.

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In order to study the lipid dependence of glucose-6-phosphatase the lipid composition of microsomes from rat liver and hepatoma was modified using lipid exchange proteins. It was shown that the enzyme activity depends on the presence of phosphatidyl ethanolamine and phosphatidyl serine, but is unaffected by the enrichment of the microsomes with phosphatidyl choline. On the basis of the data obtained it was assumed that the aminophospholipids are required for the functioning of the protein carrier; however, they do not affect the activity of the catalytic component of the glucose-6-phosphatase system on the inner surface of the microsomal membrane.

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The ability of lipid exchange proteins to introduce foreign phospholipids into intact microsomes was used for a study of the lipid dependence of rat liver cytochrome P-450. Cytochrome P-450 was converted into inactive cytochrome P-420 by treatment of rat liver microsomes with lysophosphatidylcholine. When such microsomes were incubated with phosphatidylcholine in the presence of lipid exchange proteins the lysophosphatidylcholine was partly replaced by phosphatidylcholine and the inactive cytochrome P-450 was reactivated. Similar incubation of the inactivated microsomes with phosphatidylethanolamine did not lead to reactivation of the enzyme.

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The lipid composition of rat liver microsomes, their "ghosts" and the reconstituted membrane hydroxylation system was investigated. The phospholipid content and composition of the reconstituted membranes were found to depend on the reconstitution method. The reconstituted membranes contained besides phospholipids also cholesterol and gangliosides. The cholesterol/phospholipid ratio of the reconstituted membranes was the same as that of the initial microsomes. Lysolecithin was shown to enhance the conversion of the active form of cytochrom P-450 to the inactive cytochrome P-420.

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Phospholipid composition of nuclei and nuclear membranes from rat liver and hepatoma-27 were investigated. Hepatoma nuclei and nuclear membranes were found to contain cardiolipin which was absent in the same fractions of rat liver. In the nuclei and nuclear membranes of hepatoma the content of sphingomyelin was higher and that of lecithin is lower than in the corresponding subcellular fractions of rat liver. The content of acid phospholipids was much higher in hepatoma nuclear membranes than those of the normal liver. The data obtained show that the general trend of lipid dedifferentiation which earlier was demonstrated for various membranes of different tumor cells is observed also in the case of nuclear membranes.

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