Glutamate as a Precursor to Other Amino Acids

Glutamate is one of the most metabolically active of all amino acids (Figure 21.1). It is a precursor to glutamine, arginine, creatine phosphate (Figure 21.3), proline, hydroxyproline, polyamines, glutathione, and -aminobutyric acid (GABA). GABA (see here), is a neurotransmitter, and is also involved in the synthesis of glutathione. In addition, glutamate itself is a neurotransmitter.

Figure 21.2 shows the sequence of reactions that converts glutamate to ornithine (a urea cycle intermediate). In this pathway, the energy-requiring reduction of glutamate to glutamic-semialdehyde (see here) is comparable to the reduction of aspartate to aspartic semialdehyde (see here) and also leads to synthesis of proline (see here). In the synthesis of proline, however, cyclization is desirable because the cyclized product can be reduced with NADPH to proline.

Proline is incorporated into procollagen, the polypeptide precursor of collagen. In procollagen, proline is converted to hydroxyproline by the enzyme procollagen proline hydroxylase (Figure 21.4). In order to carry out the conversion of procollagen to collagen, procollagen proline hydroxylase requires ascorbic acid (vitamin C), ferrous iron, molecular oxygen, and -ketoglutarate. Scurvy (caused by a vitamin C deficiency) leads to defects in connective tissue function, which are probably due to the defective synthesis or maturation of collagen in connective tissue.

In the structure of the vitamin folic acid (see here also), 6-methylpterin is linked through the amino group of p-aminobenzoic acid (PABA) to form pteroic acid, which is linked in turn via an amide to glutamate, to form pteroylmonoglutamate (see here). Naturally occurring folates may differ from this compound in the number of glutamate residues per molecule of vitamin, which ranges from three to eight or more. These residues are linked to one another, not by the familiar peptide bond but rather by a modified peptide bond between the -amino group and the -carboxyl group. .

See also: Urea Cycle (from Chapter 20), Citric Acid Cycle Intermediates in Amino Acid Metabolism, Neurotransmitters and Biological Regulators, Amino Acids

INTERNET LINKS:

> 1. Glutathione Metabolism

> 2. Valine, Leucine, and Isoleucine Biosynthesis

> 3. Glutamate Metabolism

> 4. Urea Cycle

> 5. Arginine and Proline Metabolism

> 6. Folate Biosynthesis