scholarly journals Metabolic Alterations Associated with γ-Hydroxybutyric Acid and the Potential of Metabolites as Biomarkers of Its Exposure

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 101
Author(s):  
Suryun Jung ◽  
Suji Kim ◽  
Yujin Seo ◽  
Sooyeun Lee

γ-Hydroxybutyric acid (GHB) is an endogenous short chain fatty acid that acts as a neurotransmitter and neuromodulator in the mammalian brain. It has often been illegally abused or misused due to its strong anesthetic effect, particularly in drug-facilitated crimes worldwide. However, proving its ingestion is not straightforward because of the difficulty in distinguishing between endogenous and exogenous GHB, as well as its rapid metabolism. Metabolomics and metabolism studies have recently been used to identify potential biomarkers of GHB exposure. This mini-review provides an overview of GHB-associated metabolic alterations and explores the potential of metabolites for application as biomarkers of GHB exposure. For this, we discuss the biosynthesis and metabolism of GHB, analytical issues of GHB in biological samples, alterations in metabolic pathways, and changes in the levels of GHB conjugates in biological samples from animal and human studies. Metabolic alterations in organic acids, amino acids, and polyamines in urine enable discrimination between GHB-ingested animals or humans and controls. The potential of GHB conjugates has been investigated in a variety of clinical settings. Despite the recent growth in the application of metabolomics and metabolism studies associated with GHB exposure, it remains challenging to distinguish between endogenous and exogenous GHB. This review highlights the significance of further metabolomics and metabolism studies for the discovery of practical peripheral biomarkers of GHB exposure.

2021 ◽  
Vol 478 (5) ◽  
pp. 1175-1178
Author(s):  
Herman Wolosker ◽  
Inna Radzishevsky

Promiscuous catalysis is a common property of enzymes, particularly those using pyridoxal 5′-phosphate as a cofactor. In a recent issue of this journal, Katane et al. Biochem. J. 477, 4221–4241 demonstrate the synthesis and accumulation of d-glutamate in mammalian cells by promiscuous catalysis mediated by a pyridoxal 5′-phosphate enzyme, the serine/threonine dehydratase-like (SDHL). The mechanism of SDHL resembles that of serine racemase, which synthesizes d-serine, a well-established signaling molecule in the mammalian brain. d-Glutamate is present in body fluids and is degraded by the d-glutamate cyclase at the mitochondria. This study demonstrates a biochemical pathway for d-glutamate synthesis in mammalian cells and advances our knowledge on this little-studied d-amino acid in mammals. d-Amino acids may still surprise us by their unique roles in biochemistry, intercellular signaling, and as potential biomarkers of disease.


Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2501
Author(s):  
Alberto Muñoz-Prieto ◽  
Ivana Rubić ◽  
Anita Horvatić ◽  
Renata Barić Rafaj ◽  
José Joaquín Cerón ◽  
...  

Obesity is a common problem in pet dogs, affecting half of the general population in some countries. Excess body weight causes several disorders and has a negative impact on dogs’ quality of life. The use of metabolomics allows the identification of metabolite traces from the metabolic pathways involved in pathological processes. This study aimed to evaluate salivary metabolite variations in dogs with obesity. The salivary samples of 19 dogs were analyzed using a targeted metabolomic approach, through which 234 metabolites were quantified. Of these, multivariate analysis identified 27 different metabolites altered in dogs with obesity compared with control dogs. These metabolites were mainly classified as amino acids, glycerides, sphingolipids, glycerophospholipids, and acylcarnitines. Some of the changes in these metabolites reflect the insulin resistance status related to obesity in dogs. Overall, it can be concluded that the salivary metabolome of obese dogs reflects the metabolic changes occurring in obesity and could be a source of potential biomarkers for this complex condition.


mSystems ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Sarah Vascellari ◽  
Vanessa Palmas ◽  
Marta Melis ◽  
Silvia Pisanu ◽  
Roberto Cusano ◽  
...  

To our knowledge, this is one of the few studies thus far that correlates the composition of the gut microbiota with the direct analysis of fecal metabolites in patients with Parkinson’s disease. Overall, our data highlight microbiota modifications correlated with numerous fecal metabolites. This suggests that Parkinson’s disease is associated with gut dysregulation that involves a synergistic relationship between gut microbes and several bacterial metabolites favoring altered homeostasis. Interestingly, a reduction of short-chain fatty acid (SCFA)-producing bacteria influenced the shape of the metabolomics profile, affecting several metabolites with potential protective effects in the Parkinson group. On the other hand, the extensive impact that intestinal dysbiosis has at the level of numerous metabolic pathways could encourage the identification of specific biomarkers for the diagnosis and treatment of Parkinson’s disease, also in light of the effect that specific drugs have on the composition of the intestinal microbiota.


Author(s):  
Kamila B. Muchowska ◽  
Sreejith Jayasree VARMA ◽  
Joseph Moran

How core biological metabolism initiated and why it uses the intermediates, reactions and pathways that it does remains unclear. Life builds its molecules from CO<sub>2 </sub>and breaks them down to CO<sub>2 </sub>again through the intermediacy of just five metabolites that act as the hubs of biochemistry. Here, we describe a purely chemical reaction network promoted by Fe<sup>2+ </sup>in which aqueous pyruvate and glyoxylate, two products of abiotic CO<sub>2 </sub>reduction, build up nine of the eleven TCA cycle intermediates, including all five universal metabolic precursors. The intermediates simultaneously break down to CO<sub>2 </sub>in a life-like regime resembling biological anabolism and catabolism. Introduction of hydroxylamine and Fe<sup>0 </sup>produces four biological amino acids. The network significantly overlaps the TCA/rTCA and glyoxylate cycles and may represent a prebiotic precursor to these core metabolic pathways.


2021 ◽  
Author(s):  
Shiyi Lu ◽  
Deirdre Mikkelsen ◽  
Hong Yao ◽  
Barbara Williams ◽  
Bernadine Flanagan ◽  
...  

Plant cell walls as well as their component polysaccharides in foods can be utilized to alter and maintain a beneficial human gut microbiota, but it is not known whether the...


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