Mitochondrial and peroxisomal disorders
Steve Hannigan in Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
This is a disorder of carbohydrate metabolism (the breakdown of sugars, including glucose). In this condition there is an absence or a deiciency of the pyruvate dehydrogenase complex, so the breakdown of pyruvate to form acetyl CoA is impaired. The pyruvate dehydrogenase complex consists of three separate enzymes: E1 – pyruvate decarboxylaseE2 – dihydrolipoyl transacetylaseE3 – dihydrolipoyl dehydrogenase.
Biocatalysts: The Different Classes and Applications for Synthesis of APIs
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Transaminases (or aminotransferases) are enzymes transferring an amino group (EC 2.6.1.-). In the recent past, the use of PLP-dependent ω-transaminases (ω-TA; meanwhile (R)- and (S)-selective ω-TAs are known) for the synthesis of optically pure amines gained increasing interest in connection with the synthesis of active pharmaceutical ingredients (for reviews see, e.g., Fuchs et al., 2015; Simon et al., 2014). ω-TAs catalyze the reversible amination/deamination of suited substrates to yield optically pure amines either by kinetic resolution (one amine enantiomer is converted into a ketone whereas the desired amine enantiomer is left behind) or by asymmetric synthesis starting from a prochiral ketone. In these cases, the amine donor is l-alanine that is converted to pyruvate. In order to shift the equilibrium to the product side, the keto acid is converted to lactate in presence of lactate dehydrogenase; pyruvate decarboxylase has also been used for this purpose. Alternatively pyruvate may be recycled to alanine in presence of a alanine dehydrogenase. Very promising is the recently described use of o-xylylenediamine as a low-cost non-chiral amine donor (Green et al., 2014); in addition, spontaneous polymerization of the aromaticisoindoleformed during the course of the reaction yields intensively colored derivatives which may serve as a high-throughput screening platform to identify ω-TA activities. These enzymes work not only in an aqueous buffer solution but also in organic solvents.
Protein Phosphorylation of Prolactin Target Tissue: Mammary Gland
James A. Rillema in Actions of Prolactin on Molecular Processes, 1987
The structure and control of pyruvate dehydrogenase has been well studied in liver, muscle, and adipose tissue.71 An associated protein kinase can be isolated from the enzyme complex, which phosphorylates the α subunit of the pyruvate decarboxylase components.72 The activity of this kinase is controlled by insulin73 in vivo and by a yet to be characterized soluble insulin-stimulated second messenger in vitro.74 A phosphatase has also been described.71,75 The enzymatic activity of pyruvate dehydrogenase is inactivated by phosphorylation.
High alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo
Published in Gut Microbes, 2021
Nan-Nan Li, Wei Li, Jun-Xia Feng, Bing Du, Rui Zhang, Shu-Heng Du, Shi-Yu Liu, Guan-Hua Xue, Chao Yan, Jing-Hua Cui, Han-Qing Zhao, Yan-Ling Feng, Lin Gan, Qun Zhang, Wei-Wei Zhang, Di Liu, Chen Chen, Jing Yuan
The genes encoding all of the enzymes of the Embden-Meyerhof-Parnas pathway (EMP), hexose monophosphoric acid pathway (HMP), Entner-Doudoroff (ED) pathway, and Tricarboxylic acid cycle (TCA) pathway were present in K. pneumoniae W14 and TH1. Analyses of the genome sequences revealed the determinants of hexose-metabolizing enzymes such as invertase, levansucrase, glucokinase, glucose-6-phosphate isomerase, and glucose-fructose oxidoreductase. These enzymes would enable K. pneumoniae to use sucrose, fructose, and glucose (as well as probably glycerol, mannose, raffinose, and sorbitol), then, convert acetyl-coA to acetaldehyde using MhpF and AdhE, and finally, produce alcohol through alcohol dehydrogenases (ADHs). More than 12 highly specific ADHs could catalyze the conversion of acetaldehyde to ethanol. Furthermore, most of these ORFs were also found to be actively transcribed in association with ethanol production by K. pneumoniae W14 and TH1. These results strongly suggested that the rapid production and high yield of ethanol could probably be attributed to the presence of 12 ADHs and pyruvate decarboxylase (GL003732 and GL001278, thiamine pyrophosphate protein TPP-binding domain protein [EC:4.1.1.74]), an enzyme not frequently observed in bacteria.
Manganese mitigates against hepatorenal oxidative stress, inflammation and caspase-3 activation in rats exposed to hexachlorobenzene
Published in Drug and Chemical Toxicology, 2022
Abiola S. Tijani, Olori O. David, Ebenezer O. Farombi
Manganese (Mn) is the fifth most abundant metal (Nadaska et al. 2012). It is a trace metal essential in many biological processes in animals, humans and plants. Manganese at low concentrations is important in many cellular processes but toxic at high concentrations. Exposure of humans to Mn is through diet, occupation sites and environment. For example, individuals working in industries such as mining, welding, organochemical fungicides and dry batteries manufacturing industries are occupationally exposed to Mn while people living in vicinity around industrial and high traffic areas where Mn containing exhaust from methylcyclopentadienyl manganese tricarbonyl (MMT) gasoline are discharged into the air (Cowan et al. 2009, Rugless et al. 2014) are environmentally exposed. Manganese plays critical roles in protein and energy metabolism, metabolic regulation, bone mineralization and cellular protection from reactive oxygen species (O’neal et al. 2014, Zizza et al. 2018). It is a cofactor for many metalloenzymes and as enzyme activator for their catalytic or regulatory function including superoxide dismutase and metabolic enzymes including pyruvate decarboxylase, glutamine synthetase and arginase (Sarsour et al. 2012, Burlet and Jain 2013, Yang et al. 2019). Though Mn is an important element for cellular functioning, elevated Mn exposure over a long time reportedly causes various pathophysiologic events in animals and humans (Aschner and Aschner 2005, Pfalzer and Bowman 2017). For instance, prolonged exposure to Mn has been reported to cause reproductive, renal and hepatic dysfunction as well as neurotoxicity by accumulating in the basal ganglia in humans and animals (Bakthavatsalam et al. 2014, Yang et al. 2019).
Mechanisms of action of vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) in pain: a narrative review
Published in Nutritional Neuroscience, 2023
A. M. Paez-Hurtado, C. A. Calderon-Ospina, M. O. Nava-Mesa
Vitamin B1 (thiamine, B1) functions in the body as a coenzyme named thiamine pyrophosphate, which is involved in important functions in carbohydrate metabolism, especially in nerve cells. It is the coenzyme of pyruvate decarboxylase, transketolase, and alpha‐ketoglutarate dehydrogenase and participates in the formation of acetylcholine. Moreover, blocking voltage-gated sodium channels, it regulates neural excitability in injured neurons in the dorsal root ganglion (DRG), suppressing thermal hyperalgesia and improving analgesia [68]. Details are given in the subchapters below.