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Domain 3:

Metabolism

Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of Folate Derivatives

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  • Authors: Jacalyn M. Green1, and Rowena G. Matthews2
  • Editor: Thomas J. Begley3
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Midwestern University, Downers Grove, IL 60515; 2: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216; 3: University at Albany, Rensselear, NY
  • Received 05 October 2005 Accepted 20 December 2006 Published 21 March 2007
  • Address correspondence to Rowena G. Matthews rmatthew@umich.edu
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  • Abstract:

    Many microorganisms and plants possess the ability to synthesize folic acid derivatives de novo, initially forming dihydrofolate. All the folic acid derivatives that serve as recipients and donors of one-carbon units are derivatives of tetrahydrofolate, which is formed from dihydrofolate by an NADPH-dependent reduction catalyzed by dihydrofolate reductase (FolA). This review discusses the biosynthesis of dihydrofolate monoglutamate, its reduction to tetrahydrofolate monoglutamate, and the addition of glutamyl residues to form folylpolyglutamates. and , like many microorganisms that can synthesize folate de novo, appear to lack the ability to transport folate into the cell and are thus highly susceptible to inhibitors of folate biosynthesis. The review includes a brief discussion of the inhibition of folate biosynthesis by sulfa drugs. The folate biosynthetic pathway can be divided into two sections. First, the aromatic precursor chorismate is converted to paminobenzoic acid (PABA) by the action of three proteins. Second, the pteridine portion of folate is made from GTP and coupled to PABA to generate dihydropteroate, and the bifunctional protein specified by , dihydrofolate synthetase, or folylpolyglutamate synthetase, adds the initial glutamate molecule to form dihydrofolate (HPteGlu, or dihydropteroylmonoglutamate). Bacteriophage T4 infection of has been shown to cause alterations in the metabolism of folate derivatives. Infection is associated with an increase in the chain lengths in folylpolyglutamates and particularly the accumulation of hexaglutamate derivatives.

  • Citation: Green J, Matthews R. 2007. Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of Folate Derivatives, EcoSal Plus 2007; doi:10.1128/ecosalplus.3.6.3.6

Key Concept Ranking

Aromatic Amino Acids
0.45156622
Sodium Dodecyl Sulfate
0.43443614
Cellular Processes
0.39763615
Dihydrofolate Reductase
0.35710046
Folic Acid
0.34469348
Folate Biosynthesis
0.32702354
0.45156622

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ecosalplus.3.6.3.6.citations
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/content/journal/ecosalplus/10.1128/ecosalplus.3.6.3.6
2007-03-21
2017-10-20

Abstract:

Many microorganisms and plants possess the ability to synthesize folic acid derivatives de novo, initially forming dihydrofolate. All the folic acid derivatives that serve as recipients and donors of one-carbon units are derivatives of tetrahydrofolate, which is formed from dihydrofolate by an NADPH-dependent reduction catalyzed by dihydrofolate reductase (FolA). This review discusses the biosynthesis of dihydrofolate monoglutamate, its reduction to tetrahydrofolate monoglutamate, and the addition of glutamyl residues to form folylpolyglutamates. and , like many microorganisms that can synthesize folate de novo, appear to lack the ability to transport folate into the cell and are thus highly susceptible to inhibitors of folate biosynthesis. The review includes a brief discussion of the inhibition of folate biosynthesis by sulfa drugs. The folate biosynthetic pathway can be divided into two sections. First, the aromatic precursor chorismate is converted to paminobenzoic acid (PABA) by the action of three proteins. Second, the pteridine portion of folate is made from GTP and coupled to PABA to generate dihydropteroate, and the bifunctional protein specified by , dihydrofolate synthetase, or folylpolyglutamate synthetase, adds the initial glutamate molecule to form dihydrofolate (HPteGlu, or dihydropteroylmonoglutamate). Bacteriophage T4 infection of has been shown to cause alterations in the metabolism of folate derivatives. Infection is associated with an increase in the chain lengths in folylpolyglutamates and particularly the accumulation of hexaglutamate derivatives.

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Figures

Image of Figure 1
Figure 1

NHR represents the Aminobenzoyl-glutamate substituent.

Citation: Green J, Matthews R. 2007. Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of Folate Derivatives, EcoSal Plus 2007; doi:10.1128/ecosalplus.3.6.3.6
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Figure 2

Citation: Green J, Matthews R. 2007. Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of Folate Derivatives, EcoSal Plus 2007; doi:10.1128/ecosalplus.3.6.3.6
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Image of Figure 3
Figure 3

NR and NHR represent the aminobenzoylglutamate substituent.

Citation: Green J, Matthews R. 2007. Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of Folate Derivatives, EcoSal Plus 2007; doi:10.1128/ecosalplus.3.6.3.6
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Image of Figure 4
Figure 4

NHR represents the aminobenzoylglutamate substituent.

Citation: Green J, Matthews R. 2007. Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of Folate Derivatives, EcoSal Plus 2007; doi:10.1128/ecosalplus.3.6.3.6
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Figure 5

Citation: Green J, Matthews R. 2007. Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of Folate Derivatives, EcoSal Plus 2007; doi:10.1128/ecosalplus.3.6.3.6
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Image of Figure 6
Figure 6

Hneopterin, dihydroneopterin.

Citation: Green J, Matthews R. 2007. Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of Folate Derivatives, EcoSal Plus 2007; doi:10.1128/ecosalplus.3.6.3.6
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Image of Figure 7
Figure 7

NHR represents the aminobenzoylglutamate substituent.

Citation: Green J, Matthews R. 2007. Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of Folate Derivatives, EcoSal Plus 2007; doi:10.1128/ecosalplus.3.6.3.6
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Figure 8

The first two glutamates are linked through their γ-carboxyls, while subsequent glutamyl residues are linked through their α-carboxyls. g, γ-linked peptide bonds; a, α-linked peptide bonds.

Citation: Green J, Matthews R. 2007. Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of Folate Derivatives, EcoSal Plus 2007; doi:10.1128/ecosalplus.3.6.3.6
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