A Review of Electron Transport Mechanisms in Parasitic Protozoa

The literature related to electron transport in parasitic protozoa is reviewed. Plasmodia contain oxidases sensitive to cyanide, azide, and carbon monoxide, indicating the presence of cytochrome oxidase. Succinoxidase and other flavoproteins are present as judged by the reduction of indophenol and cresyl blue in oxygen uptake studies. The presence of intermediate carriers is inferred from the inhibition of oxygen uptake by naphthoquinones. Trichomonads have a limited capacity for oxygen utilization which is insensitive to cyanide and results in hydrogen peroxide accumulation except when catalase is also present. A flavoprotein terminal oxidase is indicated, but the importance of the oxygen utilization is not known. Some strains produce hydrogen gas which is probably linked to electron transport. The organisms are essentially anaerobic and therefore depend upon coupled reactions mediated by pyridino and flavoproteins resulting in the production of reduced compounds. Trypanosomes show a variety of electron transport systems linked to oxygen. Cyanide has for many years been used to distinguish two types: a sensitive and an insensitive oxidase. In general the invertebrate or culture forms of all the trypanosomes have cyanide sensitive respiration, whereas the vertebrate forms are of two types: the lewisi group are cyanide sensitive and the brucei group are insensitive. All groups show conventional glycolysis pathways, but only the sensitive group shows active citric cycle reactions and hemoprotein spectra. Little is known of the properties of the latter which seem to differ in some respects from analogous factors of mammals. The sensitive pathway to oxygen resembles that of mammals but the insensitive pathway has some unique characteristics. Reduced Nicotinamide adenine dinucleotide (NADH)' is reoxidized principally by dihydroxyacetone phosphate to yield glycerophosphate. This is oxidized by a dehydrogenase which is probably a flavoprotein containing a sulfhydryl group and a metal linked to oxygen through an acetone soluble factor. Hydrogen peroxide is not found as it usually is in other cyanide insensitive oxidases. The electron transport system in mammals is an organized group of enzymes located in the outer membrane of the mitochondria (Cleland and Slater, 1953; Ziegler et al., 1958). A similar structure occurs in the protoplasmic membrane of bacteria (Weibull et al., 1959; Mitchell, 1959; Marr, 1960). Some protozoa contain mitochondria (Sedar and Rudzinska, 1956) which resemble those of higher animals, while others seem to have none (Anderson et al., 1956). The mammalian system is shown in Figure 1. This greatly simplified diagram shows that reduced nicotinamide nucleotides (NADPH, NADH) from the citric cycle, glycolysis, and other metabolic activities are oxidized by flavoproteins hav g as their prosthetic group flavin adenine dinucleotide (FAD). Since NADP ppears not to be involved in oxidative phosphoryl tion (Klingenberg and Biicher, 1960), the transhydrogenation is shown at the flavoprotein level (Kaplan, 1955) where the first phosphorylation of adenosine diphosphate (ADP) occurs (Lehninger, 1960). Succinate is oxidized by a specific flavoprotein called succinic dehydrogenase (Singer et al., 1956), which is part of the citric cycle of enzymes (Krebs, 1954). The flavoproteins are coupled to a complex called cytochrome reductase which includes a number of factors such as coenzyme Q, nonheme iron, cytochrome b, cytochrome cl, Slater factor, and others (Slater, 1958; Green and Hatefi, 1961) but about which considerable disagreement still exists. Since the experiments Received for publication 29 June 1962. * Laboratory of Parasitic Diseases. 1 The recommendations of the Commission on Enzymes, International Union of Biochemistry (Pergamon Press, 1961) are followed.