N-Acetyl-D-histidine

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.

To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.

A far-red fluorescence "off-on" sensing strategy is described for sequential ratiometric determination of Cu2+ and L-histidine (L-His) based on fluorescence resonance energy transfer (FRET) system. N,S,P co-doped carbon dots (N,S,P-CDs) and N-acetyl-L-cysteine functionalized gold nanoclusters (NAC-AuNCs) are used in the FRET system, which serve as energy donor and acceptor, respectively. After adding NAC-AuNCs into the solution of N,S,P-CDs, the fluorescence of N,S,P-CDs is effectively quenched, while the far-red fluorescence of NAC-AuNCs appears. Cu2+ can decrease fluorescence of NAC-AuNCs, and then L-His can effectively recover the fluorescence of NAC-AuNCs. The possible reason is that the stronger affinity between Cu2+ and L-His can pull Cu2+ away from the surface of NAC-AuNCs. Through it all, the emission intensity of N,S,P-CDs remains nearly constant, so the ratio of fluorescence intensities at 485 and 625 nm exhibits a linear correlation to the Cu2+ and L-His concentration, respectively. The sensing platform shows good selectivity towards Cu2+ and L-His with a linear range of 0.65-26.58 μM and 3.13-56.25 μM and determination limits of 0.50 μM and 0.374 μM, respectively. The proposed method has been successfully used for Cu2+ and L-His determination in real samples with satisfying results.