PMID- 2643036 OWN - NLM STAT- MEDLINE DCOM- 19890223 LR - 20190820 IS - 0166-6851 (Print) IS - 0166-6851 (Linking) VI - 32 IP - 1 DP - 1989 Jan 1 TI - De novo and salvage biosynthesis of pteroylpentaglutamates in the human malaria parasite, Plasmodium falciparum. PG - 25-37 AB - Plasmodium falciparum was shown to synthesize pteroylpolyglutamate de novo from guanosine 5'-triphosphate (GTP), p-aminobenzoate (PABA), and L-glutamate (L-Glu). The parasite also had the capacity to synthesize pteroylpolyglutamate from both intact and degradation moieties (p-aminobenzoylglutamate and pterin-aldehyde) of exogenous folate added into the growth medium. The major product was identified as 5-methyl-tetrahydroteroylpentaglutamate following exposure to pteroylpolyglutamate hydrolase and oxidative degradation of the C9-N10 bond in the molecule and identification of products by reversed-phase high performance liquid chromatography. Inhibition of pteroylpentaglutamate synthesis from the radiolabelled metabolic precursors (GTP, PABA, L-Glu) and folate by the antifolate antimalarials, pyrimethamine and sulfadoxine at therapeutic concentrations, may suggest the existence of a unique biosynthetic pathway in the malaria parasite. FAU - Krungkrai, J AU - Krungkrai J AD - Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand. FAU - Webster, H K AU - Webster HK FAU - Yuthavong, Y AU - Yuthavong Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - Netherlands TA - Mol Biochem Parasitol JT - Molecular and biochemical parasitology JID - 8006324 RN - 0 (Pterins) RN - 0 (Pteroylpolyglutamic Acids) RN - 33611-85-7 (pteroylpentaglutamic acid) RN - 39555-46-9 (5-methyltetrahydropteroylpentaglutamate) RN - 88463U4SM5 (Sulfadoxine) RN - 935E97BOY8 (Folic Acid) RN - Z3614QOX8W (Pyrimethamine) SB - IM MH - Animals MH - Chromatography, High Pressure Liquid MH - Erythrocytes/microbiology MH - Folic Acid/*analogs & derivatives/biosynthesis MH - Humans MH - Plasmodium falciparum/*metabolism MH - Pterins/biosynthesis MH - Pteroylpolyglutamic Acids/*biosynthesis MH - Pyrimethamine/pharmacology MH - Sulfadoxine/pharmacology EDAT- 1989/01/01 00:00 MHDA- 1989/01/01 00:01 CRDT- 1989/01/01 00:00 PHST- 1989/01/01 00:00 [pubmed] PHST- 1989/01/01 00:01 [medline] PHST- 1989/01/01 00:00 [entrez] AID - 0166-6851(89)90126-6 [pii] AID - 10.1016/0166-6851(89)90126-6 [doi] PST - ppublish SO - Mol Biochem Parasitol. 1989 Jan 1;32(1):25-37. doi: 10.1016/0166-6851(89)90126-6.