the parasite are focused on supporting this enormous reproductive effort. The relatively recently acquired ability to cultivate P. falciparum in vitro has greatly expanded biochemists' ability to study parasite nutrition and metabolism.

In P. falciparum, glucose can be replaced by fructose, but the parasite will not develop in vitro when another sugar, such as galactose, mannose, maltose, or ribose is substituted (Geary et al., 1985a). Although malaria parasites are capable of synthesizing the amino acids glutamate, aspartate, alanine, and leucine from glucose, they probably acquire them either through digestion of hemoglobin or from sources outside the red blood cell. Most early studies on the uptake of amino acids by malaria parasites utilized the animal parasites P. berghei, P. lophurae, P. gallinaceum, and P. knowlesi either in vivo, an approach in which experimental parameters are difficult to control, or in vitro, using less than ideal culture procedures. Observations on parasite biochemistry using cultures of P. falciparum have not always supported conclusions drawn from these flawed models.

In experiments using cultured P. falciparum, it has been shown that 13 of the 20 amino acids can be obtained from the digested erythrocyte cytosol; the parasite must receive the other seven amino acids from sources outside the erythrocyte. Selective transport facilities may exist for any or all of these amino acids in P. falciparum, but evidence from other Plasmodium species suggests that this is not the case for all amino acids. Attempts to supplement glutamine, one of the amino acids, with other metabolites have been unsuccessful. Both glutamate and glutamine are required for continuous cultivation, indicating that interconversion is limited at best.

There appears to be only one vitamin, calcium pantothenate, that is not provided by the erythrocyte but is needed by the parasite for survival. Evidence for this comes from in vitro studies using culture medium containing this vitamin (Divo et al., 1985a). The malaria parasite's requirement for para-aminobenzoic acid and folic acid is well documented. The requirement for these vitamins, found in red blood cells, is probably strain specific. Sulfonamides, which inhibit folic acid synthesis, have been used as antimalarial drugs for years. The story of folic acid metabolism is complicated, however, and not all sulfonamides are equally potent as antimalarials. Surprisingly, unlike most organisms, P. falciparum does not seem to require biotin. The ability to develop in the absence of this vitamin was demonstrated by growing the parasites in the presence of several biotin antagonists, including avidin (Geary et al., 1985b).

Pyrimidines and purines are the two main building blocks of DNA. Malaria parasites can synthesize the former de novo, but purines are a required nutrient (Gero and O'Sullivan, 1990). Hypoxanthine is the preferred purine source, but other purines readily substitute for hypoxanthine. Studies of the kinetics of DNA synthesis in P. falciparum have revealed



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement