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4 - Enzymology of aromatic amino acid decarboxylase

Published online by Cambridge University Press:  04 December 2009

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Summary

Kinetic properties of AAADC in vitro

DOPA and other substrates are decarboxylated by aromatic amino acid decarboxylase (AAADC), some biochemical properties of which are summarized inTable 4.1. AAADC purified from pig kidney occurs as a homodimer, with two catalytical sites, each of which binds a single pyridoxal phosphate (Vitamin B6) (Dominici et al. 1990). The pyridoxal phosphate co-factor is essential for catalytic activity, and the majority (80%) of AAADC in rat brain normally occurs as the holozyme (Kawasaki et al. 1992), endowed with an equimolar amount of pyridoxal phosphate. Pyridoxine is transferred across the blood–brain barrier by a saturable process and is phosphorylated in the brain by a specific kinase; brain pyridoxal phosphate concentrations can be increased by peripheral loading with pyridoxine (Spector & Shikuma 1978).

AAADC substrates form reversibly a Schiff base with the pyridoxal phosphate group. The consequent withdrawal of electrons from the amino acid moiety weakens the carbonyl bond, encouraging the irreversible loss of carbon dioxide, which is followed by release of the decarboxylated amine and recycling of the co-factor for the next catalytic cycle. Electrophilic substituents on the α-carbon decrease the reaction rate for AAADC substrates. In the case of the “suicide substrate” α-fluoromethyl-DOPA, an irreversible covalent bond is formed with the holozyme, resulting in a permanent loss of catalytic activity of the enzyme (Maycock, Aster, & Patchett 1980). Another suicide inhibitor, NSD 1015 (the α-hydrazine derivative of DOPA), is commonly used for the assay of DOPA synthesis, as reviewed in Chapter 5.

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Imaging Dopamine , pp. 45 - 53
Publisher: Cambridge University Press
Print publication year: 2009

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