Physiological and Pathophysiological Role of Cysteine Metabolism in Human Metabolic Syndrome

2021 ◽  
Vol 14 ◽  
Author(s):  
Arunachalam Muthuraman ◽  
Muthusamy Ramesh ◽  
Sohrab A. Shaikh ◽  
Subramanian Aswinprakash ◽  
Dhamodharan Jagadeesh
Keyword(s):  
Hydrogen Sulfide ◽  
Amino Acid ◽  
Pathological Condition ◽  
Post Translational Modifications ◽  
Neurodegenerative Process ◽  
Pathophysiological Role ◽  
Anti Oxidant ◽  
Sulfur Containing ◽  
Neurological System

: Cysteine is one of the major intermediate products of cellular amino-acid metabolism. It is a semi-essential amino acid for protein synthesis. Besides, it is also employed in the regulation of major endogenous anti-oxidant molecules i.e., reduced glutathione (GSH). Further, it is a precursor of multiple sulfur-containing molecules like hydrogen sulfide, lanthionine, taurine, coenzyme A and biotin. It is also one of the key molecules for post-translational modifications of various cellular proteins. In physiological conditions, it is employed in the sulfhydration process and plays a key role in the physiology modification of the inflammatory process in various organs, including the neurological system. The catabolism of cysteine is regulated by cysteine dioxygenase enzyme activity. The dysregulated conditions of cysteine and cysteine-associated hydrogen sulfide metabolism are widely employed in the acceleration of the neurodegenerative process. Moreover, the upregulation of cysteine and hydrogen sulfide synthesis occurs via the reverse trans-sulfuration process. This process helps to manage the worsening of a pathological condition of a cellular system. Moreover, it is also employed in the accumulation of homocysteine contents. Further, both cysteine and homocysteine molecules are widely accepted as biomarkers for various types of diseases. Therefore, the targets involved in the regulation of cysteine have been considered as valid targets to treat various disorders like cardiac disease, ischemic stroke, diabetes, cancer, and renal dysfunction.

scholarly journals The structural bases for agonist diversity in anArabidopsis thalianaglutamate receptor-like channel

2019 ◽  
Vol 117 (1) ◽  
pp. 752-760 ◽  
Author(s):  
Andrea Alfieri ◽  
Fabrizio G. Doccula ◽  
Riccardo Pederzoli ◽  
Matteo Grenzi ◽  
Maria Cristina Bonza ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Ligand ◽  
Physiological Processes ◽  
Structural Framework ◽  
Seedling Roots ◽  
Wound Signaling ◽  
Unique Amino Acid ◽  
Sulfur Containing

Arabidopsis thalianaglutamate receptor-like (GLR) channels are amino acid-gated ion channels involved in physiological processes including wound signaling, stomatal regulation, and pollen tube growth. Here, fluorescence microscopy and genetics were used to confirm the central role of GLR3.3 in the amino acid-elicited cytosolic Ca2+increase inArabidopsisseedling roots. To elucidate the binding properties of the receptor, we biochemically reconstituted the GLR3.3 ligand-binding domain (LBD) and analyzed its selectivity profile; our binding experiments revealed the LBD preference forl-Glu but also for sulfur-containing amino acids. Furthermore, we solved the crystal structures of the GLR3.3 LBD in complex with 4 different amino acid ligands, providing a rationale for how the LBD binding site evolved to accommodate diverse amino acids, thus laying the grounds for rational mutagenesis. Last, we inspected the structures of LBDs from nonplant species and generated homology models for other GLR isoforms. Our results establish that GLR3.3 is a receptor endowed with a unique amino acid ligand profile and provide a structural framework for engineering this and other GLR isoforms to investigate their physiology.

scholarly journals Identification of MET10-932 and Characterization as an Allele Reducing Hydrogen Sulfide Formation in Wine Strains of Saccharomyces cerevisiae

2010 ◽  
Vol 76 (23) ◽  
pp. 7699-7707 ◽  
Author(s):  
Angela Linderholm ◽  
Kevin Dietzel ◽  
Marissa Hirst ◽  
Linda F. Bisson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Hydrogen Sulfide ◽  
Amino Acid ◽  
Sulfate Reduction ◽  
Reductase Activity ◽  
Laboratory Strain ◽  
Sulfite Reductase ◽  
Genetic Determinant ◽  
Colony Color

ABSTRACT A vineyard isolate of the yeast Saccharomyces cerevisiae, UCD932, was identified as a strain producing little or no detectable hydrogen sulfide during wine fermentation. Genetic analysis revealed that this trait segregated as a single genetic determinant. The gene also conferred a white colony phenotype on BiGGY agar (bismuth-glucose-glycine-yeast agar), which is thought to indicate low basal levels of sulfite reductase activity. However, this isolate does not display a requirement for S-containing amino acids, indicating that the sulfate reduction pathway is fully operational. Genetic crosses against known mutations conferring white colony color on BiGGY agar identified the gene leading to reduced H2S formation as an allele of MET10 (MET10-932), which encodes a catalytic subunit of sulfite reductase. Sequence analysis of MET10-932 revealed several corresponding amino acid differences in relation to laboratory strain S288C. Allele differences for other genes of the sulfate reduction pathway were also detected in UCD932. The MET10 allele of UCD932 was found to be unique in comparison to the sequences of several other vineyard isolates with differing levels of production of H2S. Replacing the MET10 allele of high-H2S-producing strains with MET10-932 prevented H2S formation by those strains. A single mutative change, corresponding to T662K, in MET10-932 resulted in a loss of H2S production. The role of site 662 in sulfide reduction was further analyzed by changing the encoded amino acid at this position. A change back to threonine or to the conservative serine fully restored the H2S formation conferred by this allele. In addition to T662K, arginine, tryptophan, and glutamic acid substitutions similarly reduced sulfide formation.

Role of Hydrogen Sulfide and Sulfur-Containing Amino Acids in Regulation of Tone of Smooth Muscles of the Vascular Wall in Rats

2010 ◽  
Vol 42 (2) ◽  
pp. 104-109 ◽  
Author(s):  
A. V. Mel’nik ◽  
N. I. Voloshchouk ◽  
N. O. Pentyuk ◽  
K. O. Zaichko
Keyword(s):  
Amino Acids ◽  
Hydrogen Sulfide ◽  
Smooth Muscles ◽  
Vascular Wall ◽  
Sulfur Containing

scholarly journals Yin and Yang in Post-Translational Modifications of Human D-Amino Acid Oxidase

2021 ◽  
Vol 8 ◽  
Author(s):  
Silvia Sacchi ◽  
Valentina Rabattoni ◽  
Matteo Miceli ◽  
Loredano Pollegioni
Keyword(s):  
Amino Acid ◽  
Enzymatic Activity ◽  
Serine Racemase ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Post Translational Modifications ◽  
Functional Relationships ◽  
Yin And Yang ◽  
The Central Nervous System

In the central nervous system, the flavoprotein D-amino acid oxidase is responsible for catabolizing D-serine, the main endogenous coagonist of N-methyl-D-aspartate receptor. Dysregulation of D-serine brain levels in humans has been associated with neurodegenerative and psychiatric disorders. This D-amino acid is synthesized by the enzyme serine racemase, starting from the corresponding L-enantiomer, and degraded by both serine racemase (via an elimination reaction) and the flavoenzyme D-amino acid oxidase. To shed light on the role of human D-amino acid oxidase (hDAAO) in D-serine metabolism, the structural/functional relationships of this enzyme have been investigated in depth and several strategies aimed at controlling the enzymatic activity have been identified. Here, we focused on the effect of post-translational modifications: by using a combination of structural analyses, biochemical methods, and cellular studies, we investigated whether hDAAO is subjected to nitrosylation, sulfhydration, and phosphorylation. hDAAO is S-nitrosylated and this negatively affects its activity. In contrast, the hydrogen sulfide donor NaHS seems to alter the enzyme conformation, stabilizing a species with higher affinity for the flavin adenine dinucleotide cofactor and thus positively affecting enzymatic activity. Moreover, hDAAO is phosphorylated in cerebellum; however, the protein kinase involved is still unknown. Taken together, these findings indicate that D-serine levels can be also modulated by post-translational modifications of hDAAO as also known for the D-serine synthetic enzyme serine racemase.

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