Explore chapters and articles related to this topic
Ornithine transcarbamylase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Defective activity of the enzyme is readily demonstrable in a biopsied liver [6, 7]. The gene on the X-chromosome codes for the precursor protein that is imported after translation into mitochondria. The human OTC precursor cDNA has been isolated and cloned [8]. It is localized to band p21.1 in the short arm of the X chromosome [9], just proximal to the locus for Duchenne muscular dystrophy. The genes for glycerol kinase, adrenal insufficiency, chronic granulomatous disease, Norrie disease, and retinitis pigmentosa are all in this area, and a number of contiguous gene syndromes have resulted from deletions. Patients with these large deletions may have up to five severe genetic diseases making them extremely difficult to manage [10]. Large deletions within the OTC gene account for about 16 percent of mutations in affected males [11]. Another 10 percent have point mutations in a TaqI recognition site in exon 5 in (TCGA) which changes the code for arginine at position 109 of the mature protein to either glutamine or a stop codon and reduces enzyme activity to one percent of normal or less [12, 13]. Many other mostly private point mutations have established an enormous heterogeneity. By 2006, more than 350 mutations had been documented [13].
The Bioenergetics of Mammalian Sperm Motility
Published in Claude Gagnon, Controls of Sperm Motility, 2020
Spermatozoa are capable of metabolizing a wide range of extracellular substrates. Glucose, fructose, and mannose can be metabolized via the glycolytic pathway and the products oxidized in the mitochondrion. The ability of glycolysis to support motility under anaerobic conditions varies from species to species, e.g., it can do so effectively in bull, ram, and human spermatozoa, but not in boar or guinea pig sperm. Pyruvate, lactate, acetate, fatty acids, citric acid cycle intermediates, and amino acids can all be oxidized although not all stimulate oxygen uptake and, in many cases, their metabolism by intact cells is limited by permeability barriers. These data have been extensively reviewed.3-5,19 Glycerol 3-phosphate will stimulate a greater rate of oxygen uptake than any other substrate in rat, ram, and boar spermatozoa, but it is not oxidized at all by human or rabbit spermatozoa and only slowly by rhesus monkey spermatozoa.20 It is possible that glycerol 3-phosphate may arise in the female reproductive tract through the hydrolysis of seminal glyceryl phosphoryl choline.21 Intriguingly, the capacity for glycerol 3-phosphate oxidation parallels the susceptibility of these species to the male contraceptive α-chlorohydrin. Glycerol is metabolized after phosphorylation by glycerol kinase, and it is oxidized much more slowly than glycerol 3-phosphate.3,22
Future Strategies for Commercial Biocatalysis
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Robert E. Speight, Karen T. Robins
Enzyme immobilisation and fusion protein generation strategies were both adopted in a one-pot four-enzyme system for the synthesis of dihydroxyacetone phosphate from glycerol (Fig. 1.2; Hartley et al., 2017). This work achieved in situ regeneration of ATP using acetate or pyruvate kinase for repeated phosphorylation of glycerol using glycerol kinase. The cofactor recycling was enhanced through novel fusion protein strategies that tethered the cofactor to the enzymes resulting in increased efficiencies (Scott et al., 2015). This one-pot system was coupled to an aldolase for the production of various chiral sugars. The one-pot enzyme cascade from glycerol to dihydroxyacetone phosphate including in situ ATP regeneration. The generation of dihydroxyacetone phosphate from glycerol-3-phosphate can be catalysed either by glycerol phosphate oxidase or by glycerol-3-phosphate dehydrogenase along with NAD+ reduction. The most efficient system avoided the need for additional cofactor recycling by following the glycerol phosphate oxidase path and included catalase to covert the potentially enzyme destabilising hydrogen peroxide back to oxygen and water. Reactions are not all balanced in the figure for simplicity.Adapted from Hartley et al. (2017).
Glucokinase as an emerging anti-diabetes target and recent progress in the development of its agonists
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Yixin Ren, Li Li, Li Wan, Yan Huang, Shuang Cao
To study the targeting of GK in the liver, researchers first used standard Cre‐LoxP‐based gene targeting strategies to knock out the liver-specific expression sequence of GK in mice22. The results showed that the mice were normal at birth, and their fasting blood glucose levels increased with age. Six weeks later, the mice developed hyperglycaemia, and impaired glucose tolerance was detected. In another group of mice, overexpression of liver GK increased the intracellular levels of glucose 6-phosphate and glycogen, as well as the activity of L-pyruvate kinase. These findings suggested that overexpression of GK could directly improve glycolysis and glycogen synthesis in vivo23. It was also found that a high-fat diet in the GK-overexpressing mice did not cause diabetes symptoms in the short term24. However, the mice showed impaired glucose tolerance after 6 months and mild hyperglycaemia, hyperinsulinemia, and hypertriglyceridaemia at 12 months. Moreover, the GK-overexpressing mice gained more weight than those in the control group, eventually leading to glucose intolerance and reduced insulin sensitivity. The results of these experiments indicated that the levels of GK in the liver are closely related to the blood glucose levels, and the absence of GK in the liver leads to the development of hyperglycaemia. Furthermore, high levels of GK expression in the liver can induce hypoglycaemia in the short term; nevertheless, high levels of GK expression in the long term are also associated with the risk of glucose intolerance.
Plasma glycerol levels in men with hypertriglyceridemia
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2021
The additional blood samples were collected in lithium-heparin tubes. After centrifugation two plasma samples were collected and stored at −20 °C until analysis. Free plasma glycerol was determined using the Free Glycerol Determination Kit (Sigma Aldrich FG0100) according to the manufacturer’s protocol. In short, glycerol is phosphorylated by glycerol kinase into glycerol-1-phosphate. Glycerol-1-phosphate is then oxidized by glycerol phosphate oxidase to dihydroxyacetone phosphate and hydrogen peroxidase. In the final step peroxidase catalyzes the enzymatic coupling of H2O2 with 4-aminoantioyrine which produces a quinoneimine dye that shows an absorbance maximum at 540 nm. Absorbance was measured using a plate reader spectrophotometer (Thermo Fischer Scientific Ascent).
Functional profiles of coronal and dentin caries in children
Published in Journal of Oral Microbiology, 2018
Christine A Kressirer, Tsute Chen, Kristie Lake Harriman, Jorge Frias-Lopez, Floyd E Dewhirst, Mary A Tavares, Anne CR Tanner
Dentin caries (DC) Threonine synthase in S. mitis was the dominant gene observed for coronal caries (aforementioned). While not significantly different in overall levels between clinical groups, genes for ADS mapped to several species in dentin caries including S. sanguinis: dentin caries (DC) 14.3, caries-free (CF) 9.8 and coronal caries (CC) 4.7 (Figure 3d), A. naeslundii (DC 3.0, CC 0.6, CF 0.5) and A. massiliensis (DC 3.0, CC 0.3, CF 0.04). Other taxa with ADS genes in only dentin caries included S. wiggsiae (DC 4.0), Streptococcus australis (DC 1.9) and A. rimae (DC 1.4). Genes to glycerol kinase mapped mainly to S. sanguinis but levels were similar between clinical groups (DC 3.5, CC 3.9, CF 2.7). Other taxa that glycerol kinase genes mapped to in dentin caries included: Rothia aeria (DC 3.4, CC 1.6, CF 0.4), P. denticola (DC 2.4) R. dentocariosa (DC 2.1, CC 1.5, CF 0.1) and S. australis (DC 1.1, CC 0.1).