The metabolism of the fourth main group of cellular constituents, namely fatty acids and fats, phospholipids, terpenoids and steroids (see reference 266), is closely linked with those of the other groups, particularly with carbohydrates (via acetyl CoA) and proteins (see Figs. 1 and 5). Understandably, less extensive work has been done so far in this field than in those previously discussed. Claims for abnormal lipids in human neoplastic material have been made by Kosaki et al.150 (malignolipin) and by Rapport et al.209 (cytolipin H). Of the enzymes involved in lipid anabolism and catabolism, the activity of those participating in fatty acid synthesis may be decreased, as the fatty acid and phospholipid formation (cf. reference 255) was found to be markedly diminished, at least in the Novikoff hepatoma (see also Ashmore, Weber and Landau 15). The content in phospholipids of the same tumor was low 254 in comparison with regenerating and normal liver but in addition the turnover rate of the phosphate moiety of the lipid was considerably depressed when relating it to normal liver of fasting animals which also showed a loss of the phospholipid. With regard to the catabolic enzymes the activity level of esterases (ali-esterases) has been reported to fall during the development of the neoplastic state of tissues,110 but it is difficult to assess the significance of all these changes in the overall fate of the tumor cell, unless they are carefully correlated with the altered metabolic pathways of energy and acyl CoA production. Moreover, Mendel and Myers et al179 speculated on the basis of results with inhibitors that ali-esterases had lost their significance in animals but were still essential for "lower forms of life" such as bacteria and tumor cells.

It would take one too far away from the theme under review if the enzymes concerned with the metabolism of steroids were to be given even small consideration. But it should be remembered that those which have hormonal activity may be participating in hydrogen transfer, as mentioned briefly before.284 Of course, the imbalance of estrogens and androgens in cancerous organs under their control could be due in part at least to disturbances of their synthesis and degradation. This recalls the difference in activity levels between tumors and normal tissue of another esterase, namely β-glucuronidase, which Fishman et a/.98 found strikingly elevated in a number of human neoplasms and above normal in the vaginal fluid of a large percentage of women with cancer of the uterine cervix.98 A study of the localization of the enzyme by histochemical means 94 showed its presence in the cytoplasm but not in the nuclei of tumor cells. This increase is reminiscent of phosphomonoe-sterases or phosphatases, which occur in two forms, I and II, with alkaline and acid optima of activity respectively. The latter is present in relatively large amounts in patients with disseminated carcinoma of the prostate,95110 whereas the former (consisting of a Mg sensitive and Mg insensitive type) was found to be increased in primary and transplanted liver tumors 8 as the magnesium insensitive enzyme. One cannot leave the lipid metabolism without mentioning lipoproteins which play such a vital part in the proper functioning of cell membranes controlling the entry and exit of a great number of ions and compounds, and last but not least, of drugs. As these membranes must be the seat of enzymes, not necessarily connected with lipid metabolism, and of immuno-bodies, the behaviour of normal and abnormal cell surfaces has received increasing attention. This intriguing subject will be taken up again further on.