AciduriaDeficiencyCitrullineArginineOrnithineCitric acidUrea-cycle enzymeCytosolEssential aminoGeneReactionSuccinicThreoninePhenylalanineDehydrogenaseNitrogenMetabolismGlutamateMutationsCharacterizationProteinDisordersDeficienciesNitricFattyCarbamylCondensationLiverDegradationHyperammonemiaDefectsNucleotideUrineFatsBreakdownOrganic
Aciduria16
- Argininosuccinic aciduria is an inherited disorder that causes ammonia to accumulate in the blood. (medlineplus.gov)
- Argininosuccinic aciduria usually becomes evident in the first few days of life. (medlineplus.gov)
- An infant with argininosuccinic aciduria may be lacking in energy (lethargic) or unwilling to eat, and have a poorly controlled breathing rate or body temperature. (medlineplus.gov)
- Complications from argininosuccinic aciduria may include developmental delay and intellectual disability. (medlineplus.gov)
- Argininosuccinic aciduria occurs in approximately 1 in 70,000 to 218,000 newborns. (medlineplus.gov)
- Mutations in the ASL gene cause argininosuccinic aciduria. (medlineplus.gov)
- In people with argininosuccinic aciduria, argininosuccinate lyase is dysfunctional or missing. (medlineplus.gov)
- This buildup of ammonia damages the brain and other tissues and causes neurological problems and other signs and symptoms of argininosuccinic aciduria. (medlineplus.gov)
- More than 130 mutations in the ASL gene have been found to cause argininosuccinic aciduria. (medlineplus.gov)
- Identification of a common novel mutation in Saudi patients with argininosuccinic aciduria. (medlineplus.gov)
- A mouse model of argininosuccinic aciduria: biochemical characterization. (medlineplus.gov)
- Patients with citrullinemia, caused by a deficiency of AS , or argininosuccinic aciduria, caused by a deficiency of AL , will manifest marked increases of blood citrulline and argininosuccinate, respectively. (nih.gov)
- On 12 December 2017, orphan designation (EU/3/17/1952) was granted by the European Commission to PhaseRx Ireland, Ltd, Ireland, for modified messenger ribonucleic acid encoding human argininosuccinate lyase enzyme encapsulated into lipid nanoparticles (also known as PRX-ASL) for the treatment of argininosuccinic aciduria. (web.app)
- Mutations in this gene result in the autosomal recessive disorder argininosuccinic aciduria, or argininosuccinic acid lyase deficiency. (antibodypedia.com)
- Primary urea cycle disorders (UCDs) include carbamoyl phosphate synthase (CPS) deficiency, ornithine transcarbamylase (OTC) deficiency, argininosuccinate synthetase deficiency (citrullinemia), argininosuccinate lyase deficiency (argininosuccinic aciduria), arginase deficiency (argininemia), and N -acetylglutamate synthetase (NAGS) deficiency. (msdmanuals.com)
- Succinic semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydoxybutyric aciduria or gamma-hydoxybutyric aciduria , is a rare autosomal recessive disorder [1] of the degradation pathway of the inhibitory neurotransmitter γ-aminobutyric acid , or GABA . (wikidoc.org)
Deficiency17
- The neonatal presentation of argininosuccinate (ASA) lyase deficiency is consistent with the clinical manifestations of hyperammonemia. (medscape.com)
- ASA lyase deficiency is an autosomal recessive genetic disorder. (medscape.com)
- The gene for ASA lyase deficiency is located on chromosome 7 and has been mapped to the locus 7q11.2. (medscape.com)
- Nagamani SC, Erez A, Lee B. Argininosuccinate lyase deficiency. (medscape.com)
- Long-term outcome of patients with argininosuccinate lyase deficiency diagnosed by newborn screening in Austria. (medscape.com)
- An enzyme is missing resulting in a deficiency in biotin. (nsu.govt.nz)
- Argininosuccinate lyase (ASL) deficiency: mutation analysis in 27 patients and a completed structure of the human ASL gene. (medlineplus.gov)
- Urinary orotic acid generally is very elevated in babies with OTC deficiency and normal or even low in infants with CPS deficiency. (nih.gov)
- Patients with OTC deficiency have increased excretion of orotic acid because carbamyl phosphate spills into the cytoplasm, where it enters the pathway of pyrimidine synthesis. (nih.gov)
- To distinguish between CPS deficiency and OTC deficiency, orotic acid measurement is helpful because accumulation of carbamoyl phosphate in OTC deficiency results in its alternative metabolism to orotic acid. (msdmanuals.com)
- Opening a window on lysosomal acid lipase deficiency: Biochemical, molecular, and epidemiological insights. (viictr.org)
- Ravicti is indicated for use as adjunctive therapy for chronic management of adult and paediatric patients ≥2 months of age with urea cycle disorders (UCDs) including deficiencies of carbamoyl phosphate-synthase-I (CPS), ornithine carbamoyltransferase (OTC), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), arginase I (ARG) and ornithine translocase deficiency hyperornithinaemia-hyperammonaemia homocitrullinuria syndrome (HHH) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. (europa.eu)
- Patients with ornithine carbamoyltransferase deficiency lack 'ornithine carbamoyltransferase', one of the liver enzymes that are needed to get rid of excess nitrogen. (europa.eu)
- Tyrosinemia type I is caused by a deficiency of fumarylacetoacetase (FAH), one of the last enzymes in aromatic amino acid metabolism. (medicalhomeportal.org)
- SSADH deficiency is caused by an enzyme deficiency in GABA degradation. (wikidoc.org)
- However, because of the deficiency, the final intermediate of the GABA degradation pathway, succinic semialdehyde, accumulates and cannot be oxidized to succinic acid and is therefore reduced to gamma-hydroxybutyric acid (GHB) by gamma-hydroxybutyric dehydrogenase. (wikidoc.org)
- A deficiency of the latter enzyme leads to higher levels of proline and a buildup of the intermediate breakdown product pyrroline-5-carboxylate, causing the signs and symptoms of hyperprolinemia type II.Hyperprolinemia is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. (mdwiki.org)
Citrulline3
- Some cells synthesize argininosuccinic acid from citrulline and aspartic acid and use it as a precursor for arginine in the urea cycle or citrulline-NO cycle. (wikipedia.org)
- Argininosuccinic acid is produced from the condensation of citrulline and aspartate by a synthetase enzyme. (medscape.com)
- ASLD is typically established with elevation of plasma citrulline together with elevated argininosuccinic acid in the plasma or urine. (bomiprot.org)
Arginine5
- It is then cleaved to produce fumarate and arginine by a lyase enzyme. (medscape.com)
- The specific role of the argininosuccinate lyase enzyme is to start the reaction in which the amino acid arginine, a building block of proteins, is produced from argininosuccinate, the molecule that carries the waste nitrogen collected earlier in the urea cycle. (medlineplus.gov)
- In cells throughout the body, the argininosuccinate lyase enzyme is also involved in moving (transporting) arginine into cells to make a compound called nitric oxide. (medlineplus.gov)
- Argininosuccinate lyase (ASL) catalyzes the fourth reaction in this cycle, resulting in the breakdown of argininosuccinic acid to arginine and fumarate. (bomiprot.org)
- Plasma concentrations of glutamine and alanine, the major nitrogen-carrying amino acids, usually are high and that of arginine is low. (nih.gov)
Ornithine4
- Important products and enzymes in ornithine metabolism (see text for pathway detail). (medscape.com)
- An inner mitochondrial membrane transporter directs ornithine to the transcarbamoylase enzyme to keep intramatrix ornithine levels low. (medscape.com)
- As with other mitochondrial carrier family proteins, the ornithine carrier is composed of 300 amino acids that constitute 3 repeated motifs of approximately 100 amino acids each. (medscape.com)
- Ornithine can also be produced in the matrix by aminotransferase, but this enzyme is active in pericentral venous hepatocytes rather than in periportal hepatocytes. (medscape.com)
Citric acid1
- Argininosuccinic acid is a precursor to fumarate in the citric acid cycle via argininosuccinate lyase. (wikipedia.org)
Urea-cycle enzyme3
- Urea-cycle enzyme activity is regulated by dietary protein. (medscape.com)
- In part, glucagon and cyclic adenosine 3',5'-monophosphate (cAMP) regulate urea-cycle enzyme transcription. (medscape.com)
- The multiple primary causes of hyperammonemia, specifically the urea cycle enzyme deficiencies, vary in manifestation, diagnostic features, and management. (medscape.com)
Cytosol2
- A total of 5 enzymes in 2 subcellular compartments (mitochondrial matrix and cytosol) convert ammonia into urea, which is excreted by the kidney (see image below). (medscape.com)
- Argininosuccinate is cleaved in the cytosol by argininosuccinate lyase ( AL ), which is coded on human chromosome 7 ( Fig. 44-6 , reaction 4). (nih.gov)
Essential amino7
- The formation of propionyl CoA in human metabolism is derived from many sources, chiefly catabolism of a number of essential amino acids (isoleucine, valine, threonine, methionine). (medscape.com)
- essential and non-essential amino acids. (studysmarter.co.uk)
- Essential amino acids are amino acids necessary for an organism's survival. (studysmarter.co.uk)
- Since we cannot synthesize these essential amino acids by ourselves, we must obtain them from our diets. (studysmarter.co.uk)
- Non-essential amino acids are amino acids that can be synthesized by the body. (studysmarter.co.uk)
- The table below shows the essential and non-essential amino acids in adult humans. (studysmarter.co.uk)
- Although histidine is on the list of essential amino acids, some textbooks consider it to be conditionally essential, as it is only fully essential in childhood. (studysmarter.co.uk)
Gene8
- The ASL gene provides instructions for making an enzyme called argininosuccinate lyase, which is needed for the fourth step of the urea cycle. (medlineplus.gov)
- The ASL gene provides instructions for making the enzyme argininosuccinate lyase. (medlineplus.gov)
- Mutations in the ASL gene may result in an argininosuccinate lyase enzyme that is unstable, misshapen, or quickly broken down. (medlineplus.gov)
- Deletion hotspot in the argininosuccinate lyase gene: association with topoisomerase II and DNA polymerase alpha sites. (medlineplus.gov)
- This enzyme is coded on human chromosome 9, where a 63-kb gene comprising 14 exons is located. (nih.gov)
- This gene encodes a member of the lyase 1 family. (antibodypedia.com)
- Hyperprolinemia type I is caused by a mutation in the PRODH gene, which codes for the enzyme proline oxidase . (mdwiki.org)
- Hyperprolinemia type II is caused by a mutation in the ALDH4A1 gene, for the enzyme 1-pyrroline-5-carboxylate dehydrogenase . (mdwiki.org)
Reaction4
- The enzyme that catalyzes the reaction is argininosuccinate synthetase. (wikipedia.org)
- This enzyme begins the process of degrading proline by starting the reaction that converts it to pyrroline-5-carboxylate. (mdwiki.org)
- This enzyme helps to break down the pyrroline-5-carboxylate produced in the previous reaction, converting it to the amino acid glutamate . (mdwiki.org)
- The conversion between proline and glutamine, and the reverse reaction controlled by different enzymes, are important factors required to maintain proper metabolism and protein production. (mdwiki.org)
Succinic4
- Argininosuccinate Succinic acid Ganetzky, Rebecca D. (wikipedia.org)
- Under normal conditions, SSADH works with the enzyme GABA transaminase to convert GABA to succinic acid . (wikidoc.org)
- Succinic acid can then be utilized for energy production via the Krebs cycle . (wikidoc.org)
- GABA is metabolized by successive transamination and oxidation to yield succinic semialdehyde and succinic acid respectively via the catalyzing effects of GABA transaminase . (wikidoc.org)
Threonine1
- Aminotransferases exist for all amino acids except threonine and lysine. (medmuv.com)
Phenylalanine2
- eg PKU - without this enzyme an amino acid (called phenylalanine) rises to harmful levels and can lead to developmental delay. (nsu.govt.nz)
- Treatment consists of a diet low in the protein-derived amino acids tyrosine and phenylalanine, and nitisinone (NTBC), a medication that inhibits upstream tyrosine degradation, thereby preventing the formation of succinylacetone. (medicalhomeportal.org)
Dehydrogenase2
- A pair of principal enzymes, glutamate dehydrogenase and glutamine synthatase, are found in all organisms and effect the conversion of ammonia into the amino acids glutamate and glutamine, respectively. (medmuv.com)
- Hyperprolinemia is a condition which occurs when the amino acid proline is not broken down properly by the enzymes proline oxidase or pyrroline-5-carboxylate dehydrogenase , causing a buildup of proline in the body. (mdwiki.org)
Nitrogen6
- Urea cycle defects with resulting hyperammonemia are due to deficiencies of the enzymes involved in waste nitrogen metabolism. (medscape.com)
- It also synthesizes proteins and nitrogen-containing compounds like hormones and nucleotide bases using amino acids present in the body. (studysmarter.co.uk)
- Nitrogen fixation is carried out by bacterial nitrogenases forming reduced nitrogen, NH4+ which can then be used by all organisms to form amino acids. (medmuv.com)
- Reduced nitrogen enters the human body as dietary free amino acids, protein, and the ammonia produced by intestinal tract bacteria. (medmuv.com)
- In the absence of this enzyme, excess nitrogen accumulates in the body in the form of ammonia, which can be toxic at high levels, especially to the brain. (europa.eu)
- Phenylbutyrate works by being converted into phenylacetate in the body and combining with the amino acid glutamine, which contains nitrogen, to form a substance that can be removed from the body by the kidneys. (europa.eu)
Metabolism8
- Such processes are collectively referred to as amino acid metabolism . (studysmarter.co.uk)
- Then, we will dive into the definition of amino acid metabolism. (studysmarter.co.uk)
- After, we will learn about how the function of Enzymes in amino acid metabolism. (studysmarter.co.uk)
- Lastly, we will explore some amino acid metabolism disorders. (studysmarter.co.uk)
- Now, let's look at the definition of amino acid metabolism. (studysmarter.co.uk)
- Amino acid metabolism refers to the sum of all chemical reactions in which amino acids are broken down and synthesized for vital processes in the body. (studysmarter.co.uk)
- Overview of Amino Acid and Organic Acid Metabolism Disorders The kidneys actively reabsorb significant amounts of amino acids. (msdmanuals.com)
- These are due to the accumulation of delta-aminolevulinic acid, whose metabolism is inhibited by succinylacetone. (medicalhomeportal.org)
Glutamate1
- GABA is synthesized in a single step from its precursor glutamate by glutamic acid decarboxylase . (wikidoc.org)
Mutations2
- Other mutations replace one protein building block (amino acid) with another amino acid in the argininosuccinate lyase enzyme. (medlineplus.gov)
- In people of Arab ancestry, two common mutations replace the amino acid glutamine with a premature stop signal at position 116 (written as Gln116Ter or Q116*) or position 354 (written as Gln354Ter or Q354*) in the argininosuccinate lyase enzyme. (medlineplus.gov)
Characterization1
- 1. O'Brien, W. E. and Barr, R. H. (1981) 'Argininosuccinate lyase: purification and characterization from human liver', Biochemistry, 20(7), pp. 2056-2060. (bomiprot.org)
Protein3
- Protein is typically digested and absorbed in the form of amino acids . (studysmarter.co.uk)
- The activity of this enzyme is directly related to dietary protein. (nih.gov)
- Treatment of urea cycle disorders is dietary protein restriction that still provides adequate amino acids for growth, development, and normal protein turnover. (msdmanuals.com)
Disorders1
- These enzyme deficiencies lead to disorders with nearly identical clinical presentations. (medscape.com)
Deficiencies1
- Orphan designation of glyceryl tri-(4-phenylbutyrate) had been granted in the United States of America for the maintenance treatment of patients with deficiencies in enzymes of the urea cycle. (europa.eu)
Nitric1
- Requirement of argininosuccinate lyase for systemic nitric oxide production. (medscape.com)
Fatty1
- Other sources of propionyl CoA include odd chain-length fatty acids and the side chain of cholesterol, although these probably contribute very little in relation to the amino acid sources. (medscape.com)
Carbamyl1
- also at this step, N-acetylglutamate exerts its regulatory control on the mediating enzyme, carbamyl phosphate synthetase (CPS). (medscape.com)
Condensation1
- A peptide bond is an amide bond formed between amino acids by the condensation of -NH 2 and -COOH, releasing H 2 O. (studysmarter.co.uk)
Liver1
- This enzyme primarily participates in the urea cycle, a series of reactions that occur in liver cells. (medlineplus.gov)
Degradation1
- An inherited metabolic disorder that is characterized by impaired synthesis and degradation of amino acids. (mcw.edu)
Hyperammonemia1
- Studies suggest that the underlying cause of the hyperammonemia is the inhibition of N -acetylglutamate synthase (NAGS) activity by free propionic acid. (medscape.com)
Defects1
- Defects of amino acid transport in the renal tubule include cystinuria and Hartnup disease, which are discussed elsewhere. (msdmanuals.com)
Nucleotide1
- Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. (lookformedical.com)
Urine1
- Quantitative plasma amino acid analysis, urine organic acid analysis. (medicalhomeportal.org)
Fats2
- Alongside Carbohydrates , fats, and Nucleic Acids , proteins are one of the Organic Molecules that make up most life forms. (studysmarter.co.uk)
- Without these enzymes energy cannot be converted from fats and can lead to coma and death. (nsu.govt.nz)
Breakdown1
- In particular, individuals with conditions that cause elevated levels of lactic acid in the blood, such as lactic acidemia, are likely to have elevated proline levels, because lactic acid inhibits the breakdown of proline. (mdwiki.org)
Organic1
- An amino acid is a group of Organic Molecules with an amino group (-NH 2 ), a carboxyl group (-COOH), and a side chain (called R group ) unique to every amino acid. (studysmarter.co.uk)