For the first time, a procedure is described for the quantitative analysis of free alpha-keto acid content in human neutrophils (PMNs) relative to single cell number by reversed-phase fluorescence high-performance liquid chromatography. The procedure is minimally invasive and is unsurpassed in the quality of PMN separation, ease of sample preparation as well as sample stability. This method can satisfy the rigorous demands for an ultra-sensitive, comprehensive and rapid intracellular alpha-keto acid analysis in particularly for the surveillance of severe diseases as well as cellular or organ dysfunction.
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http://dx.doi.org/10.1016/s1570-0232(03)00163-6 | DOI Listing |
Int J Mol Sci
November 2024
Analytical Research and Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA 01810, USA.
Glycan structures of glycoproteins and glycolipids on the surface glycocalyx and luminal sugar layers of intracellular membrane compartments in human cells constitute a key interface between intracellular biological processes and external environments. Sialic acids, a class of alpha-keto acid sugars with a nine-carbon backbone, are frequently found as the terminal residues of these glycoconjugates, forming the critical components of these sugar layers. Changes in the status and content of cellular sialic acids are closely linked to many human diseases such as cancer, cardiovascular, neurological, inflammatory, infectious, and lysosomal storage diseases.
View Article and Find Full Text PDFTalanta
March 2025
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, School of Chemistry, Central China Normal University, Wuhan, 430079, PR China. Electronic address:
Pyruvic acid (PA) is an α-keto acid which exert important biological and pathological functions. The current PA profiling assays are mainly based on the ultraviolet spectroscopy and electrochemical biosensor, requiring killing cells and destroying tissues which limit their application in living cells. Optical imaging provides nondestructive powerful and detective tools to better understand the physiological and pathological role of PA in living systems.
View Article and Find Full Text PDFCell Biochem Funct
September 2024
Department of Health and Human Performance, High Point University, High Point, North Carolina, USA.
Elevated circulating branched-chain amino acids (BCAA) have been linked with the severity of insulin resistance across numerous populations, implicating heightened BCAA metabolism as a potential therapy for insulin resistance. Recently, the angiotensin II type 1 receptor (AT1R) inhibitor Valsartan (VAL) was identified as a potent inhibitor of branched-chain alpha-keto acid dehydrogenase kinase (BCKDK), a negative regulator of BCAA metabolism. This work investigated the effect of VAL on myotube metabolism and insulin sensitivity under both insulin sensitive and insulin resistant conditions.
View Article and Find Full Text PDFJCI Insight
August 2024
Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA.
Dihydrolipoamide dehydrogenase (DLD) deficiency is a recessive mitochondrial disease caused by variants in DLD, the E3 subunit of mitochondrial α-keto (or 2-oxo) acid dehydrogenase complexes. DLD disease symptoms are multisystemic, variably manifesting as Leigh syndrome, neurodevelopmental disability, seizures, cardiomyopathy, liver disease, fatigue, and lactic acidemia. While most DLD disease symptoms are attributed to dysfunction of the pyruvate dehydrogenase complex, the effects of other α-keto acid dehydrogenase deficiencies remain unclear.
View Article and Find Full Text PDFSubcell Biochem
July 2024
Department of Biochemistry, Semmelweis University, Budapest, Hungary.
The present work delves into the enigmatic world of mitochondrial alpha-keto acid dehydrogenase complexes discussing their metabolic significance, enzymatic operation, moonlighting activities, and pathological relevance with links to underlying structural features. This ubiquitous family of related but diverse multienzyme complexes is involved in carbohydrate metabolism (pyruvate dehydrogenase complex), the citric acid cycle (α-ketoglutarate dehydrogenase complex), and amino acid catabolism (branched-chain α-keto acid dehydrogenase complex, α-ketoadipate dehydrogenase complex); the complexes all function at strategic points and also participate in regulation in these metabolic pathways. These systems are among the largest multienzyme complexes with at times more than 100 protein chains and weights ranging up to ~10 million Daltons.
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