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chapter 17

Protein and Amino Acid Metabolism

R— CH— COO-

Pyridoxal phosphate

Aldimine

Ketimine

r

H

2

0 , H+

o

'»R— C— COO~

a-K eto acid

NH,

■CH.— o — ®

F IG U R E 17-4

Mechanism of the first phase of transamination. The -NH

2

group from the amino acid is transferred to pyridoxal

phosphate, with formation of the corresponding «-keto acid. The second phase occurs by the reversal of the first phase

reactions and is initiated by formation of a Schiff base with the a-keto acid substrate and pyridoxamine phosphate. The

transamination cycle is completed with formation of the corresponding «-amino acid and pyridoxal phosphate.

to the second substrate, the a-keto acid. Thus, pyridoxal

phosphate functions as a carrier of amino groups and as an

electron sink by facilitating dissociation of the a-hydrogen

of the amino acid (Figure 17-4). In the overall reaction, the

amino acid transfers its amino group to pyridoxal phos-

phate and then to the keto acid through formation of pyri-

doxamine phosphate as intermediate.

Pyridoxal phosphate is also the prosthetic group of

amino acid decarboxylases, dehydratases, desulfhydrases,

racemases, and aldolases, in which it participates through

its ability to render labile various bonds of an amino acid

molecule (Figure 17-5). Several drugs (Figure 17-6) in-

hibit pyridoxal phosphate-dependent enzymes. Isonico-

tinic hydrazide (used in the treatment of tuberculosis) and

hydralazine (a hypertensive agent) react with the alde-

hyde group of pyridoxal (free or bound) to form pyridoxal

hydrazones, which are eliminated in the urine. Isonico-

tinic acid hydrazide is normally inactivated in the liver

by acetylation; some individuals are “slow acetylators”

(an inherited trait) and may be susceptible to pyridoxal

deficiency from accumulation of the drug. Cycloserine

(an amino acid analogue and broad-spectrum antibiotic)

also combines with pyridoxal phosphate.

Role o f Specific Tissues in Amino Acid Metabolism

The specific roles of various tissues and organs and their

interdependence on amino acid metabolism are discussed

here. An overview of this topic is given in Chapter 22.

In the post absorptive state, maintenance of steady-state

concentrations of plasma amino acids depends on release

F IG U R E 17-5

Labilization of bonds of an amino acid bound to pyridoxal

phosphate-containing enzymes. Given the appropriate apoenzyme, any

atom or group on the carbon atom proximal to the Schiff base can be

cleaved.