China
Africa
Explore chapters and articles related to this topic
D-2-hydroxyglutaric (DL-2-hydroxyglutaric) aciduria
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
A lymphoblast model of IDH2 gain of function disease has been developed [38] and employed to screen for potential inhibitors of the superactive enzyme. Oxalacetate was found to be the most effective inhibitor studied.
The Promise for Alzheimer’s Disease Treatment
Published in Dilip Ghosh, Pulok K. Mukherjee, Natural Medicines, 2019
Víctor Andrade, Leonardo Guzmán-Martínez, Nicole Cortés, Ricardo B. Maccioni
Oxaloacetate (3-carboxy-3-oxopropanoic acid, OAA) is a natural chemical that participates in Krebs cycle and acts as a glutamate scavenger (Zlotnik et al. 2012). It is found in blueberries, blackberries, tangerines and plums, and in vegetables as spinach, beets and quinoa (Simpson et al. 2009; Ghosh Das and Savage 2013; Lin et al. 2016; Siener et al. 2016). Legumes and nuts also have high OAA content (Chai and Liebman 2005). Due to its bioenergetic, anti-inflammatory and neurogenetic properties, OAA has been postulated as a possible treatment for AD (Wilkins et al. 2014). An incipient phase 1, non-randomised clinical trial is now recruiting subjects with diagnosis of probable AD to verify safety and tolerance (Table 14.2). In a previous study, a very modest cohort of 6 participants showed that twice daily treatment of 100 mg of OAA for 4 weeks was safe and well-tolerated (Swerdlow et al. 2016). Another natural compound related to mitochondria metabolism is S-equol (7-hydroxy-3-(4′-hydroxyphenyl)-chroman). It is an oestrogen receptor β (ERβ) agonist, present predominantly in soy (Setchell et al. 2005; Jackson et al. 2011). It has been found in the brains of AD patients, evidence of a decrease in mitochondria activity by dysfunction (Hirai et al. 2001; Swerdlow 2012). S-equol has been proposed as a potential treatment for this pathology. A phase 2, randomised, double-blind trial is recruiting AD subjects to evaluate safety and tolerability in addition to mitochondrial activity and cognitive functions (Table 14.2).
Distribution and Biological Functions of Pyruvate Carboxylase in Nature
Published in D. B. Keech, J. C. Wallace, Pyruvate Carboxylase, 2018
Although its concentration in liver is very low,959 oxaloacetate is the product and/or substrate of many enzymes.893 Together with PEP and pyruvate, oxaloacetate is a key component in the interlocking of glycolysis, gluconeogenesis, the Krebs tricarboxylic acid cycle, and several related processes. The localization, then, of one of the enzymes linking two members of this "triangle" has been of considerable interest in understanding the regulation of this metabolic crossroads, particularly in view of the fact that the relative proportions of PEP carboxykinase in the mitochondria vs. the cytosol vary so markedly from species to species (for a review, see Söling and Kleineke804).
Preoperative Carbohydrate Loading in Gynecological Patients Undergoing Combined Spinal and Epidural Anesthesia
Published in Journal of Investigative Surgery, 2020
Numerous clinical and epidemiological studies have shown the predictive potential of hand grip strength regarding short- and long-term mortality and morbidity [34]. In patients, impaired grip strength is an indicator of increased postoperative complications, increased length of hospitalization, a higher rehospitalization rate, and a decreased physical status. As muscle function reacts early to nutritional deprivation, hand grip strength has also become a popular marker of nutritional status and is increasingly being employed as outcome variable in nutritional intervention studies [34]. The present study showed increased grip strength of the dominant hand both at 1 h after surgery and before entering the operating room in the CHO group. This could be related to the rapid recovery after surgery of the CHO group. Our data also showed that patients receiving preoperative carbohydrate loading have improved pyruvate and lactate/pyruvate ratios and diminished lactate after operation. Lactate is the product of the anaerobic metabolism of glucose, while pyruvate comes from aerobic metabolism and plays an important role in three different pathways of glucose metabolism [35]. The fasting status increases gluconeogenesis, with corresponding increases in lactate. On the other hand, providing carbohydrate beverages may decrease the gluconeogenic pathway and increase the usability of oxaloacetate [35].
Is air pollution a potential cause of neuronal injury?
Published in Neurological Research, 2019
Yu Ji, Christopher Stone, Longfei Guan, Changya Peng, Wei Han
As it occurs in the periphery, the purpose of gluconeogenesis may be described generally as, along with glycogenolysis, the maintenance of energy homeostasis through the generation of glucose for use by extrahepatic tissues during prolonged fasts, a task it achieves through de novo synthesis of glucose from precursors such as glycerol, amino acids, pyruvate, and lactate [31]. Accomplishing this requires the coordinated function of a series of enzyme-catalyzed reactions, most of which are also involved in glycolysis, and simply run in reverse while serving the anabolic purpose of gluconeogenesis. In addition to these reversible steps, however, gluconeogenesis possesses several unique, irreversible enzymes that serve as important regulatory checkpoints in the coordination of cellular energy metabolism with overall organismal energy homeostasis: pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), fructose 1,6-bisphosphatase (FBP), and glucose 6-phosphatase (G6PC) [32]. PC catalyzes the ATP-intensive first of these regulatory reactions within mitochondria by carboxylating pyruvate to yield oxaloacetate. Oxaloacetate is subsequently decarboxylated, shuttled out of the mitochondrion, and then phosphorylated by PEPCK in a reaction that requires GTP. After an intervening sequence of reversed glycolysis reactions that generates fructose 1,6-bisphosphate, FBP yields fructose 6-phosphate, which is isomerized to glucose 6-phosphate and, finally, dephosphorylated to yield glucose de novo; these latter two dephosphorylations both require ATP.
Aberrant lipid metabolism as a therapeutic target in liver cancer
Published in Expert Opinion on Therapeutic Targets, 2019
Evans D. Pope, Erinmarie O. Kimbrough, Lalitha Padmanabha Vemireddy, Phani Keerthi Surapaneni, John A. Copland, Kabir Mody
De novo fatty acid (FA) synthesis occurs in high energy or fed states. During FA synthesis, glucose is taken up in the liver where it is then converted to FAs for storage in the form of triacylglycerols (TAGs) [8]. The initial step in FA synthesis is glycolysis. Glycolysis results in the production of pyruvate from glucose [8]. This reaction takes place in the cytosol of the hepatocyte. After pyruvate has been produced, pyruvate enters into the mitochondria and is converted to citrate via the citric acid (TCA) cycle [9]. Once citrate has been formed, citrate is expelled out of the mitochondria via the citrate shuttle. Citrate is converted into oxaloacetate and acetyl CoA via ATP-citrate lyase (ACL) [9]. The oxaloacetate is further broken down into pyruvate and NADPH. The acetyl CoA and NADPH are then used for FA synthesis [9]. Acetyl CoA is converted to Malonyl CoA via ACC [10]. Malonyl CoA and Acetyl CoA are combined using FASN to help form saturated fatty acids (SFA) (palmitoyl-CoA and stearoyl-CoA) [10]. Critically, these are then converted to monounsaturated fatty acids (MUFA) palmitoleoyl-CoA and oleoyl-CoA by SCD [11]. MUFAs are critical as building blocks for membrane synthesis, prostaglandin synthesis, and as the source for TAGs. They are important to cancer cell survival via their role in the induction of autophagy, enhancement of cell membrane turnover, effecting intracellular signaling and gene transcription, and increasing energy production.