Pyruvate carboxylase deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Pyruvate carboxylase (EC 6.4.1.1) is a biotin-containing mitochondrial enzyme, which catalyzes the conversion of pyruvate to oxalacetate by CO2 fixation (Figure 48.1) [1, 2]. As in the case of other carboxylases, the reaction mechanism is a two-step process in which biotin is first carboxylated and then the carboxyl group is transferred to the acceptor, pyruvate [3, 4]. There is a separate catalytic site for each of the two steps. The enzyme is a tetramer of 500 kDa whose individual equal-sized protomers have a different structure from other biotin-containing carboxylases [5], but the highly conserved amino acid sequence at the biotin site of biotin-containing carboxylases, Ala-Met-Lys-Met is present in pyruvate carboxylase [6]. The biotin is linked to the ε amino group of the lysine.
The vitamins
Geoffrey P. Webb in Nutrition, 2019
Biotin functions as a coenzyme for several important carboxylase enzymes i.e. enzymes that add a carboxyl (COOH) group via fixation of carbon dioxide. The enzyme pyruvate carboxylase is important in gluconeogenesis (production of glucose from pyruvate and amino acids). Other carboxylase enzymes are important in fatty acid synthesis (acetyl CoA carboxylase) and the metabolism of branched chain amino acids.
Pantothenic Acid and Biotin
Judy A. Driskell, Ira Wolinsky in Sports Nutrition, 2005
Pyruvate carboxylase, propionyl-CoA carboxylase and β-methylcrotonyl-CoA carboxylase are located in mitochondria. Pyruvate carboxylase is a key enzyme in gluconeogenesis. Propionyl-CoA carboxylase catalyzes an essential step in the metabolism of isoleucine, valine, methionine, threonine, the cholesterol side chain and odd-chain fatty acids. β-Methylcrotonyl-CoA carboxylase catalyzes an essential step in leucine metabolism.
Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors
Published in Drug Delivery, 2021
Xianhu Zeng, Zhipeng Li, Chunrong Zhu, Lisa Xu, Yong Sun, Shangcong Han
Gluconeogenesis can generate free glucose from non-carbohydrate carbon substrates (such as glycerol, lactic acid, pyruvate, and glycogenic amino acids). Although it is less studied than catabolic glycolysis or oxidative phosphorylation (OXPHOS), this anabolic pathway plays the same role in controlling the aerobic glycolysis of cancer cells (Seenappa et al. 2016). The complete pathway consists of 11 enzyme-catalyzed reactions, of which there are 7 reactions that are the opposite steps of glycolysis, and 3 reactions that are not involved in gluconeogenesis: (i) the conversion of pyruvate to phosphoenolpyruvate, which is determined by the reaction that catalyzes pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK); (ii) the catalyzation of the conversion of fructose-1,6-diphosphate to fructose-6-phosphate by fructose-1,6-bisphosphatase (FBPase); (iii) the catalyzation of the conversion of glucose-6-phosphate to glucose by glucose-6-phosphatase (G6Pase) (Icard et al. 2019). PEPCK, FBPase, and G6Pase are the key enzymes that control the gluconeogenesis flux, thereby affecting glycolysis, the TCA cycle, the PPP and other branched metabolic pathways (serine biosynthesis, glycogen health, gluconeogenesis, and glutamine decomposition) (Kang et al. 2016; Icard et al. 2019).
The management of Babesia, amoeba and other zoonotic diseases provoked by protozoa
Published in Expert Opinion on Therapeutic Patents, 2023
Clemente Capasso, Claudiu T. Supuran
Among these targets, it should be mentioned a superfamily of metalloenzymes known as carbonic anhydrases (CAs), which have been demonstrated to be involved in several metabolic processes, such as gluconeogenesis, urea synthesis, and fatty acid synthesis [75–78]. Recently, our groups using bioinformatics tools verified the presence of gene encoding CAs in Toxoplasma gondii. The protozoan genome encodes for a putative α-CA, identified with the accession number XP_002365178.1, consisting of 852 amino acid residues. The C-terminal part of the protein showed all the hallmarks typifying the α-CAs (Figure 5). The alignment clearly showed that all the residues involved in the catalytic mechanism of an α-CA, such as the catalytic triad (His94, His96, and His119), the gatekeeper residues (Glu106 and Thr199), and the proton shuttle residue (His64), are conserved in the sequence of the putative α-CA identified in the genome of T. gondii. In T. gondii, the identified putative carbonic anhydrases might provide bicarbonate for the pyruvate carboxylase, an enzyme expressed in protozoan mitochondria, which utilizes bicarbonate to convert pyruvate to oxaloacetate [79].
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.
Related Knowledge Centers
- Carboxylation
- Catalysis
- Enzyme
- Magnesium
- Manganese
- Oxaloacetic Acid
- Protein
- Pyruvic Acid
- Anaplerotic Reactions
- Biotin