Helene A. Nathan

Metabolism of Folic Acid and Other Pterin-Pteridine Vitamins

Publisher Summary Pterinoid investigations have steadily extended knowledge of (1) transfer of C 1 groups, (2) biosynthetic and functional connections between folic vitamins and other nitrogenous heterocycles—purines, thymine (or thymidine), riboflavin, vitamins Bs and BIZ, and unconjugated pterins. Ever since F. G. Hopkins looked into the pigments of butterfly wings, these unconjugated pterins (for example xanthopterin and leucopterin) have been a biosynthetic enigma. The advent of folic acid complicated matters. A solution is in sight thanks to other lines of investigation converging: (1) the eye pigments of Drosophilu—classical objects of genetics—are predominantly pterins in some mutants, (2) the flagellate Crithidia fasciculata requires certain unconjugated pterins, PGA apparently being the precursor, and (3) remarkably high concentrations of pterins, some with Crithidiu-factor activity, occur in blue-green algae and are somehow involved in photosynthesis. Evidently, certain unconjugated pterins have an essential, unknown function. This chapter attempts to collate clues to new relationships and functions of pterinoids; its point of departure is the exhaustive treatment of p -aminobenzoic acid (PABA) by Wright and Taormina, and of the folic vitamin family by Stokstad and others. Uses of microbial systems and the comparative biochemistry of pterinoids are emphasized in the chapter.

Chlorpromazine Affects Permeability of Resting Cells of Tetrahymena pyriformis

Incubation of cell suspensions of Tetrahymena pyriformis with chlorpromazine increased the permeability of the cell membrane. This permeability change could be measured either biochemically by the increased entrance of a chelator or physically by change in light scattering.

General considerations in the use of microorganisms in screening antitumor agents.

The prophets mantel is easily transformed into a strait jacket or dunce cap. As microbiologists rather detached from clinical urgencies, we have cause to shy away from pronouncements. However, with a rashness incited by gratifications in providing microbial research tools for such scientists as vitamin biochemists and photobiological physicists, we shall advance some notions. Chemists can create compounds faster than biologists can test them-unless screening procedures become more effective. Two kinds of nets are necessary in an effective screening procedure: (1) one sufficiently wide to detect all classes of cytotoxic compounds, and (2) one sufficiently fine meshed to guide the choice of clinically useful compounds within a particular class of cytotoxic agents. There is no compelling reason for the coarse and the fine-meshed nets to use the same microorganisms.

ROTIFERS AS BIOLOGICAL TOOLS

The diversity of rotifer life cycles-complex even within a single specieschallenges the experimenter. Except for the ostensibly dioecious marine epizoites of the genus Seisolz (Hyman, 1951), members of the Rotifera* can reproduce parthenogenetically. Indeed, parthenogenesis is the only reproductive method observed for the bdelloids; in contrast, the monogononts can produce males intermittently and later reproduce sexually. Especially when working with the latter group, a t the outset one faces these problems: (1) selection of the stage a t which to initiate monoxenic or axenic cultures; (2) elimination of other organisms; and (3) maintenance of the rotifers, once axenized and normally growing and reproducing. Most of our studies were done with two ploimate species (order Monogonontida) : Brachionus bidentatus Anderson, 1889, ortho. mut. nov. and B. variabilis Hempel, 1896.

Inhibition of Growth of Microorganisms by Benzimidazoles.

Summary Benzimidazole and 2-ethyl-5-methyl benzimidazole inhibited the growth of 2 B12-requiring algae, Euglena gracilis, strain Z, and Ochromonas malhamensis, and of 4 B12-synthesizing bacteria, Rhizobium meliloti, R. trifolii, R. leguminosarum, and R. japonicum. Benzimidazole inhibition was complete at 5 × 10-3M concentration. The 2-ethyl-5-methyl compound inhibited the algae at 5 × 10-3M concentration; rhizobia were more sensitive. Although benzimidazole inhibition of E. gracilis was not competitive, there was, at a 108:1 ratio of inhibitor to vitamin, a relation to amount of growth which could be expressed graphically as a straight line.

Nutritional Effects of β-Methyl-Aspartate and Methyl-Malonate on Euglena gracilis and Ochromonas malhamensis.∗

Summary The following compounds do not either replace or spare the growth requirement for Vit. B12 of either E. gracilis or O. malhamensis: DL-β-methyl-aspartate, L-threo-β-methyl-aspartate, ureido-β-methyl-aspartate, N-acetyl-L-threo-β-methyl-aspartate, and methyl-malonate. Inhibition of growth of E. gracilis by benzimidazole is not annulled by β-methyl-aspartate.