N-acetyl-L-histidine, a Prominent Biomolecule in Brain and Eye of Poikilothermic Vertebrates.

Morris H Baslow,David N Guilfoyle

doi:10.3390/biom5020635

Morris H Baslow, David N Guilfoyle

Open Access

https://doi.org/10.3390/biom5020635

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Journal: Biomolecules	Publication Date: Apr 24, 2015
Citations: 23	License type: CC BY 4.0

Affiliation: Nathan Kline Institute for Psychiatric Research

Abstract

N-acetyl-l-histidine (NAH) is a prominent biomolecule in brain, retina and lens of poikilothermic vertebrates. In fish lens, NAH exhibits an unusual compartmentalized metabolism. It is synthesized from l-histidine (His) and acetyl Co-enzyme A. However, NAH cannot be catabolized by lens cells. For its hydrolysis, NAH is exported to ocular fluid where a specific acylase cleaves His which is then actively taken up by lens and re-synthesized into NAH. This energy-dependent cycling suggested a pump mechanism operating at the lens/ocular fluid interface. Additional studies led to the hypothesis that NAH functioned as a molecular water pump (MWP) to maintain a highly dehydrated lens and avoid cataract formation. In this process, each NAH molecule released to ocular fluid down its gradient carries with it 33 molecules of bound water, effectively transporting the water against a water gradient. In ocular fluid the bound water is released for removal from the eye by the action of NAH acylase. In this paper, we demonstrate for the first time the identification of NAH in fish brain using proton magnetic resonance spectroscopy (MRS) and describe recent evidence supporting the NAH MWP hypothesis. Using MRS, we also document a phylogenetic transition in brain metabolism between poikilothermic and homeothermic vertebrates.

Highlights

In this study we demonstrate that NAA and NAH can be detected separately or in mixtures of the two in phantoms as well as in brain using proton magnetic resonance spectroscopy (MRS)
In this article we show for the first time using MRS that NAH, an important osmolyte in poikilotherm brain, can be readily detected and identified in the brain of bony fish
We show that NAA, a major osmolyte in homeotherm brain, can be detected and identified in mammalian brain using this same technique

Summary

Introduction

N-acetyl-L-histidine (NAH) is a prominent biomolecule in brain, retina and lens of poikilothermic (ectothermic) vertebrates. NAH exhibits a strong phylogenetic component in that it is a major osmolyte in the brain and eye of teleost (bony) fish, amphibians and reptiles, but is present in much lower amounts in brain and other tissues of homeothermic (endothermic) vertebrates. Another acetylated amino acid, N-acetyl-L-aspartate (NAA) is a major osmolyte in brain and eye of these forms, and is present in lesser amounts in brain and eye of poikilothemic vertebrates. The phylogenetic distribution and metabolic relationships between NAH and NAA have been reviewed [1]

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