New Discoveries of Significance to the Prevention, Control, and Treatment of Leprosy
Max J. Miller, E. J. Love in Parasitic Diseases: Treatment and Control, 2020
There has been extremely rapid progress in the last 5 years in characterizing the biochemistry of M. leprae, mainly by Wheeler and associates in Great Britain.19 The organism contains most pathways normally associated with glycolosis, the tricarboxylic acid cycle, the hexose monophosphate pathway, and glycerol catabolism and the like, and a major biochemical defect which prevents it from multiplying in vitro has not been identified. On the other hand, generally the metabolic activities of M. leprae are low, compared to cultivable mycobacteria. Catalase appears to be absent from M. leprae and the rate of de novo purine synthesis is very low, compared with the rate of purine scavenging. The organism has predominantly glycine in its cell wall peptidoglycans, rather than alanine. M. leprae lacks dicarboxymycolates which are present in most other mycobacteria and also seems to lack tuberculostearic acid.
Biosynthesis and Genetics of Lipopolysaccharide Core
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
The basic structure of the LPS core OS of Escherichia coli and Salmonella enterica serovar Typhimurium (hereafter referred to simply as Salmonella*) was elucidated in the 1960s and early 1970s. As structural and analytical methods have advanced, the fine structural details of these core OS have been established. The structure of the core OS is made up of a backbone of 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo), heptose, and hexose sugars (Fig. 1). The core OS structure is divided into inner (Kdo and heptose) and outer (hexose) core regions. The structure of the inner core is well conserved among members of the family Enterobacteriaceae, while the outer core can vary between strains. Until recently, only one core OS type was known for Salm onella spp. A variant structure is found in serovar Arizonae Ilia (serotype 062) (2). In E. coli, however, there are five distinct core structures, termed K-12, Rl, R2, R3, and R4. Further advancements in analytical chemical/biochemical techniques will undoubtedly enhance our understanding of these structures, especially with respect to nonstoichiometric substitutions (e.g., phosphate) of the core.
Functions of the Liver
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
The breakdown of glucose to carbon dioxide and water with the production of energy is called glycolysis. Glucose catabolism proceeds by two pathways, either by cleavage to trioses producing pyruvic acid and lactic acid (the Embden–Meyerhof pathway) or via oxidation and decarboxylation to pentose (hexose monophosphate shunt). The net energy gain from glycolysis is three molecules of ATP. Pyruvic acid enters the citric acid cycle by conversion to acetic acid with the loss of one molecule of CO2. The citric acid cycle generates 12 molecules of ATP for every molecule of acetic acid. In total, 38 molecules of ATP are produced by the aerobic breakdown of glucose to pyruvate and its incorporation into the citric acid cycle. Pyruvic acid can be formed from the metabolism of amino acids and fat. Glycolysis produces acetyl CoA, which is used as a substrate for lipogenesis and subsequently the production of triglycerides. Another important property of the liver is the formation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) via the pentose phosphate pathway. Two NADPH molecules and ribose-5-phosphate are produced from one glucose molecule. NADPH is required for microsomal and mitochondrial hydroxylation of steroid hormones and biotransformation of many drugs.
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
In the human body, GK is mainly concentrated in pancreatic cells and liver cells, as well as the hypothalamus and gastrointestinal tract. It is mainly involved in the first step of glucose metabolism, as the first rate-limiting enzyme. It catalyses the phosphorylation of hexose (e.g. D-glucose, D-fructose, and D-mannitose) to hexose 6-phosphate (e.g. glucose 6-phosphate, fructose 6-phosphate, and mannitose 6-phosphate) (Figure 3)8. However, GK has a distinct molecular structure and active function compared with hexokinase. Its molecular weight is usually half or lower than that of other hexokinases and has a higher Km (Michaelis–Menten constant) value (8 mM). Its reactivity is not affected by the phosphorylated product glucose 6-phosphate, ensuring that the blood glucose within the physiological range is fully phosphorylated.
Detrimental effects of fructose on mitochondria in mouse motor neurons and on C. elegans healthspan
Published in Nutritional Neuroscience, 2022
Divya Lodha, Sudarshana Rajasekaran, Tamilselvan Jayavelu, Jamuna R. Subramaniam
To better understand the modus operandi of fructose in the elicitation of a multitude of dysfunctions in the mitochondria (Figures 2–5) as reported by us here, increased osmolarity of the culture medium due to addition of high fructose9 was investigated. For this, mannitol, an impermeable, hexose sugar alcohol, which is not metabolized but increases the osmolarity non-ionically, was used in a range of concentrations similar to fructose, and the mitochondrial bioenergetics were measured. At 6 hrs, 1% mannitol, and 0.5%, and 1% fructose had no impact on the cells (Figure 3). But 5% (275 mM) mannitol and 5% (277 mM) fructose affected the cells adversely (Figure 3). A significant proportion of the cells had detached and obtained a circular morphology indicative of cell death in both, as reported for mannitol treatment of endothelial cells29 after 6 hrs exposure. While the effects of 5% mannitol were similar to 5% fructose, 1% fructose fared worse than 1% mannitol, thus, providing evidence that fructose is more harmful (Figure 3).
Modulatory effect of isopulegol on hepatic key enzymes of glucose metabolism in high-fat diet/streptozotocin-induced diabetic rats
Published in Archives of Physiology and Biochemistry, 2021
Karunanithi Kalaivani, Chandrasekaran Sankaranarayanan
Liver is an important organ and plays a major role in maintaining glucose homeostasis by regulating glucose utilization and production. Hexokinase is one of the important key glycolytic and insulin sensitive enzymes (Vats et al. 2003). It catalyses the phosphorylation of glucose to glucose 6-phosphate, thereby channelizing glucose through the glycolytic pathway. The activity of hexokinase was decreased in diabetic rats leading to decreased glucose removal from blood. Pentose phosphate pathway (hexose monophosphate shunt) is an alternative route for the oxidation of glucose (Zhang et al. 2000). This pathway is found in the cytosol is responsible for the biosynthesis of NADPH and ribose-bi-phosphate. NADPH is required for the biosynthesis of glutathione, a non-enzymatic antioxidant. The activity of G6PDH, a rate limiting enzyme of this pathway is greatly decreased in diabetic rats. Administration of isopulegol at the effective dose of 100 mg/kg b.w. increased these enzyme activities thereby improving glucose utilization and oxidation. Our results are in line with Kurup et al. who reported that Averrhoa bilimbi ameliorated glycolytic enzymes in STZ-induced diabetic rats (Kurup and SM 2017).
Related Knowledge Centers
- Biochemistry
- Chemistry
- Fructose
- Glucose
- Monosaccharide
- Starch
- Carbon
- Hydroxy Group
- Carbonyl Group
- Hydrogen