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Nutritional Deficiencies
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Deepa Bhupali, Fernando D. Testai
Thiamine is a cofactor for: Transketolase: This enzyme links glycolysis to the hexose monophosphate shunt (Figure 17.1). The hexose monophosphate shunt is required for the synthesis of: Pentoses (such as ribose phosphate): necessary for the synthesis of nucleotides.Nicotinamide adenine dinucleotide phosphate (NADP): necessary for the synthesis of fatty acids, steroids, and antioxidants.Pyruvate dehydrogenase E1: Pyruvate dehydrogenase is a complex formed by three enzymes (E1, E2, and E3). This complex links the glycolytic pathway with the Krebs cycle. E1 requires thiamine pyrophosphate as a cofactor.Alpha-ketoglutarate dehydrogenase: This enzyme participates in the Krebs' cycle and is involved in the conversion of alpha-ketoglutarate to succinyl-CoA. The deficiencies of this enzyme and E1 lead to decreased adenosine triphosphate (ATP) production and cellular dysfunction.
Functions of the Liver
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
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.
Phosphoribosylpyrophosphate synthetase and its abnormalities
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
The molecular basis of the disease in the patients with superactive enzyme activity is an altered PRPP synthetase structure. Activity may be three times that of the normal enzyme [3]. In one of the families studied, increased enzyme activity was demonstrable only at low concentrations of phosphate, and there was diminished responsiveness to feedback inhibition by purine nucleotides [2]. In another family, an elevated level of enzyme-specific activity was demonstrable over a wide range of phosphate concentrations, and feedback inhibition was normal [3]. The amounts of immunoreactive enzyme protein were normal [26]. These observations indicate the presence in normal amounts of a protein in which structural alteration leads to increased specific activity. The data are consistent with the presence of two important sites on the enzyme: a catalytic site altered by one mutation and a regulatory site altered by the other. In one patient, the altered structure affected both catalytic and regulatory sites [6]. The enzyme may have increased affinity for the substrate ribose-5-phosphate [27].
The study of metabolism and metabolomics in a mouse model of silica pulmonary fibrosis based on UHPLC-QE-MS
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2022
Min Qiu, Ling Qin, Yonghe Dong, Junbing Ma, Zheng Yang, Zhixiang Gao
The pentose phosphate pathway, a form of glucose oxidative decomposition, is the main pathway for the synthesis of phosphoribose and reduced nicotinamide adenine dinucleotide phosphate, which plays an important antioxidant role in the body [16]. Abnormal pentose phosphate metabolism may indicate a disorder in the normal antioxidant stress function, and the levels of deoxyribose 5-phosphate, d-ribose and gluconic acid involved in this pathway were increased to different degrees. Deoxyribose 5-phosphate and d-ribose jointly synthesize d-ribose 5-phosphate, which plays an important role in energy production, and gluconic acid is a glucose-related metabolite [16,17]. Elevated levels of deoxyribose 5-phosphate, d-ribose and gluconic acid indicate a dysregulated pentose phosphate pathway that leads to impaired antioxidant function [18].
Immune metabolism: a bridge of dendritic cells function
Published in International Reviews of Immunology, 2022
Yuting Sun, Liyu Zhou, Weikai Chen, Linhui Zhang, Hongbo Zeng, Yunxia Sun, Jun Long, Dongping Yuan
There are two glycolytic branches during the conversion of glucose (Figure 2). First, glucose-derived G6P can produce ribose-5-phosphate which promotes nucleotide and ribosome biosynthesis through the pentose phosphate pathway (PPP). This pathway also allows conversion of nicotinamide adenine dinucleotide phosphate (NADP) to reduced nicotinamide adenine dinucleotide phosphate (NADPH), which is significant for fatty acid synthesis that promotes the expansion of endoplasmic reticulum (ER) and Golgi required for TLR-driven DCs activation [22]. Second, under anaerobic conditions, pyruvate derived from G6P is reduced by NADH to lactate in the presence of lactate dehydrogenase (LDH) accompanying the production of nicotinamide adenine dinucleotide (NAD+). Then NAD+ can be further used for glycolysis and promotes ATP production. Interestingly, the energy produced by OXPHOS and glycolysis is derived from glucose, but the efficiency is significantly different. OXPHOS generates up to 36 molecules of ATP per molecule of glucose, anaerobic glycolysis produces only 2 molecules of ATP, and aerobic glycolysis produces 4 molecules of ATP because a small portion of glucose is converted to pyruvate, thereby participating in the TCA in the presence of oxygen [21, 30, 32, 35, 36].
The Prophylactic Activity of Punica granatum L. mesocarp Protects Preadipocytes against Ribosylated BSA-Induced Toxicity
Published in Journal of the American College of Nutrition, 2021
P. Ramlagan, P. Rondeau, V. S. Neergheen, E. Bourdon, T. Bahorun
The management of glucose and ribose levels in diabetics, from the standpoint of insulin and enzymes involved in the formation of ribose-5-phosphate from glucose, is of paramount importance. Pomegranate polyphenols as well as the different pomegranate parts extracts are known to regulate glucose level by increasing insulin level and insulin sensitivity (62). Moreover, the non-edible part, i.e. the peel and flower, of the pomegranate improved insulin sensitivity, thus reducing fasting blood glucose level in high fat and high sucrose diet-induced obese mice (63). These findings indicate that PME, which shares similar polyphenolic profile as the peel and flower, is likely to be an insulin sensitizer. Punicalagin, which is an abundant polyphenolic compound in PME (14), in addition to other pomegranate polyphenolic compounds have been shown to delay production of glucose, by suppressing the activities of α-amylase and α-glucosidase (64–66). To our knowledge, no study has demonstrated the modulatory effect of PME or polyphenolic compounds on the activity of the enzymes involved in formation of ribose-5-phosphate from glucose. However, based on their effects on different enzymes, such as α-amylase and α-glucosidase, it is likely that polyphenolic compounds present in PME modulate the activity of isomerase, thus the formation of 5-ribose phosphate from glucose; a claim that must be further investigated.