Mammalian forebrain ketimine reductase identified as μ-crystallin; potential regulation by thyroid hormones.

Abstract:

:Ketimine reductase (E.C. 1.5.1.25) was purified to apparent homogeneity from lamb forebrain by means of a rapid multi-step chromatography protocol. The purified enzyme was identified by MS/MS (mass spectrometry) as μ-crystallin. The identity was confirmed by heterologously expressing human μ-crystallin in Escherichia coli and subsequent chromatographic purification of the protein. The purified human μ-crystallin was confirmed to have ketimine reductase activity with a maximum specific activity similar to that of native ovine ketimine reductase, and was found to catalyse a sequential reaction. The enzyme substrates are putative neuromodulator/transmitters. The thyroid hormone 3,5,3'-l-triiodothyronine (T3) was found to be a strong reversible competitive inhibitor, and may have a novel role in regulating their concentrations. μ-Crystallin is also involved in intracellular T3 storage and transport. This research is the first to demonstrate an enzyme function for μ-crystallin. This newly demonstrated enzymatic activity identifies a new role for thyroid hormones in regulating mammalian amino acid metabolism, and a possible reciprocal role of enzyme activity regulating bioavailability of intracellular T3.

journal_name

J Neurochem

authors

Hallen A,Cooper AJ,Jamie JF,Haynes PA,Willows RD

doi

10.1111/j.1471-4159.2011.07220.x

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

379-87

issue

3

eissn

0022-3042

issn

1471-4159

journal_volume

118

pub_type

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