Figure 46.1. Sites of action of MTX and MTX polyglutamates (MTX(glu)N).

Figure 46.1

Sites of action of MTX and MTX polyglutamates (MTX(glu)N). MTX enters cells by either the reduced-folate carrier (1) or the membrane folate binding protein (2). MTX is then polyglutamylated by the enzyme folypolyglutamate synthetase (3). MTX (glu)n is a potent inhibitor of dihydrofolate reductase (DHFR) (4). MTX polyglutamates are hydrolyzed to MTX in the lysosome by γ-glutamyl hydrolase (GGH) (5). FH2 = dihydrofolate; FH4 = tetrahydrofolate; CH2FH4 = N5, N10-methylene tetrahydrofolate; dUMP = deoxyuridylate; TMP = thymidine monophosphate; GGH = [γ]-glutamyl hydrolase.

From: Chapter 46, Folate Antagonists

Cover of Holland-Frei Cancer Medicine
Holland-Frei Cancer Medicine. 5th edition.
Bast RC Jr, Kufe DW, Pollock RE, et al., editors.
Hamilton (ON): BC Decker; 2000.
© 2000, BC Decker Inc.

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