AciduriaUrea cycleArgininosuccinate lyaseSynthetaseArginineCitrullineIncrease plasma ammonia levelsAutosomal recessive disorderHyperammonemiaEssential aminoRemoval of ammoniaAccumulation of ammoniaProteinAccumulatesMetabolismToxicThreonineDeficiencyEnzymeElevationSupplementationExcessAlanineDietaryRenalIncorporationCarbohydrateAmino acid glutamineGlutamineProteinsMoleculeLevelsAmideForm
Aciduria20
- Argininosuccinic aciduria is an inherited disorder that causes the accumulation of argininosuccinic acid (also known as "ASA") in the blood and urine. (wikipedia.org)
- Argininosuccinic aciduria may become evident in the first few days of life because of high blood ammonia, or later in life presenting with "sparse" or "brittle" hair, developmental delay, and tremors. (wikipedia.org)
- An infant with argininosuccinic aciduria may seem lethargic or be unwilling to eat, have poorly controlled breathing rate or body temperature, experience seizures or unusual body movements, or go into a coma. (wikipedia.org)
- Complications from argininosuccinic aciduria may include developmental delay and mental retardation. (wikipedia.org)
- Mutations in the ASL gene cause argininosuccinic aciduria. (wikipedia.org)
- Argininosuccinic aciduria belongs to a class of genetic diseases called urea cycle disorders. (wikipedia.org)
- citation needed] In argininosuccinic aciduria, the enzyme argininosuccinate lyase, involved in the conversion of arginino succinate to arginine within the urea cycle, is damaged or missing. (wikipedia.org)
- Ammonia is especially damaging to the nervous system, so argininosuccinic aciduria causes neurological problems as well as eventual damage to the liver. (wikipedia.org)
- Argininosuccinic aciduria occurs in approximately 1 in 70,000 live births. (wikipedia.org)
- 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)
- Argininosuccinic aciduria occurs in approximately 1 in 70,000 to 218,000 newborns. (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)
- Mutations in this gene result in the autosomal recessive disorder argininosuccinic aciduria, or argininosuccinic acid lyase deficiency. (antibodypedia.com)
- 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)
- Erez A, Nagamani SC, Lee B. Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond. (medscape.com)
Urea cycle16
- The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia. (wikipedia.org)
- The hepatic urea cycle is the major route for waste nitrogen disposal, which is chiefly generated from protein and amino acid metabolism. (medscape.com)
- however, this reaction is secondarily impaired and results in a 50% reduction of the overall capacity of the urea cycle to dispose of ammonia. (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)
- Since N -acetylglutamate (NAG) is the allosteric activator of carbamoylphosphate synthase, the entry step into the urea cycle, decreased ureagenesis occurs with accumulation of free ammonia. (medscape.com)
- BUPHENYL (sodium phenylbutyrate) Tablets is a prescription medicine that can be taken by mouth and BUPHENYL (sodium phenylbutyrate) Powder is a prescription medicine that can be taken by mouth or feeding tube for the long-term management of high blood levels of ammonia (hyperammonemia) caused by a condition called a urea cycle disorder (UCD). (horizonbyyourside.com)
- The encoded protein forms a cytosolic homotetramer and primarily catalyzes the reversible hydrolytic cleavage of argininosuccinate into arginine and fumarate, an essential step in the liver in detoxifying ammonia via the urea cycle. (antibodypedia.com)
- UCDs are a group of disorders caused by genetic mutations that result in a deficiency in one of the six enzymes that catalyze the urea cycle, which can lead to an excess accumulation of ammonia in the bloodstream, a condition known as hyperammonemia. (biospace.com)
- The urea cycle ( Fig. 44-6 ) mediates the removal of ammonia as urea in the amount of 10 to 20 g per day in the healthy adult. (nih.gov)
- Adjunct in the chronic management of urea cycle disorders involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase, or argininosuccinic acid synthetase. (empr.com)
- The urea cycle is a series of biochemical reactions that occur primarily in the liver, which converts toxic ammonia produced by the breakdown of protein and other nitrogen-containing molecules in the human body into urea for excretion 3 . (acertx.com)
- BUPHENYL® (sodium phenylbutyrate) Tablets for oral administration and BUPHENYL® (sodium phenylbutyrate) Powder for oral, nasogastric, or gastrostomy tube administration are indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders (UCDs) involving deficiencies of carbamoyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). (horizonbyyourside.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)
- Treatment of urea cycle disorders is dietary protein restriction that still provides adequate amino acids for growth, development, and normal protein turnover. (msdmanuals.com)
- 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)
- Ornithine carbamoyltransferase deficiency is one of the inherited disorders known as 'urea cycle disorders', which cause ammonia to accumulate in the blood. (europa.eu)
Argininosuccinate lyase2
- 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)
Synthetase3
- the first waste nitrogen molecule derives from free ammonia in the carbamyl phosphate synthetase (CPS) reaction. (medscape.com)
- BUPHENYL only treats high blood levels of ammonia in patients with carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC) and argininosuccinic acid synthetase (AS) deficiencies. (horizonbyyourside.com)
- ACER-001 is a nitrogen-binding agent in development for use as adjunctive therapy in the chronic management of patients with UCDs involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). (biospace.com)
Arginine5
- Compound 5 is fumaric acid generated in the reaction that converts ASA to arginine (6), which is mediated by ASA lyase. (medscape.com)
- Arginine is not produced, excess nitrogen is not converted to urea for excretion, and ammonia accumulates in the body. (medlineplus.gov)
- Plasma concentrations of glutamine and alanine, the major nitrogen-carrying amino acids, usually are high and that of arginine is low. (nih.gov)
- Use in combination with dietary protein restriction and/or amino acid supplementation (eg, essential amino acids, arginine, citrulline, protein-free calorie supplements). (empr.com)
- The diagnosis of citrin deficiency is established in an individual with characteristic biochemical findings (in general, increased blood or plasma concentration of ammonia, plasma or serum concentration of citrulline and arginine, plasma or serum threonine-to-serine ratio, and serum concentration of pancreatic secretory trypsin inhibitor) and identification of biallelic pathogenic variants in SLC25A13 . (nih.gov)
Citrulline4
- Plasma concentrations of ammonia (>150 μmol/L) and citrulline (200-300 μmol/L) are elevated. (wikipedia.org)
- Under normal circumstances, citrulline is condensed with aspartic acid to form argininosuccinic acid (ASA), which is a reaction mediated by the argininosuccinic acid synthase enzyme. (medscape.com)
- In vitro evidence in rat brains suggests that accumulated citrulline and ammonia impair the organ's antioxidant capacity. (medscape.com)
- Periodic measurement of plasma concentration of ammonia and citrulline, and serum concentration of PSTI for all phenotypes associated with citrin deficiency. (nih.gov)
Increase plasma ammonia levels2
- Corticosteroids may increase plasma ammonia levels. (empr.com)
- Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels. (horizonbyyourside.com)
Autosomal recessive disorder1
- Methylmalonic acidemia (MMA) due to methylmalonyl-CoA mutase deficiency (OMIM #251,000) is an autosomal recessive disorder of organic acid metabolism associated with life-threatening acute metabolic decompensations and significant neuropsychological deficits. (bvsalud.org)
Hyperammonemia3
- Studies suggest that the underlying cause of the hyperammonemia is the inhibition of N -acetylglutamate synthase (NAGS) activity by free propionic acid. (medscape.com)
- Hyperammonemia possible with haloperidol and valproic acid. (empr.com)
- There have been published reports of hyperammonemia being induced by haloperidol and by valproic acid. (horizonbyyourside.com)
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)
Removal of ammonia1
- 1,2 The current treatment of patients with UCDs consists of dietary management to limit ammonia production in conjunction with medications that provide alternative pathways for the removal of ammonia from the bloodstream. (biospace.com)
Accumulation of ammonia1
- These individuals can have an accumulation of ammonia in the bloodstream only during periods of illness or other stress, or mild intellectual disability or learning disabilities with no evidence of elevated ammonia levels. (medlineplus.gov)
Protein4
- Protein is typically digested and absorbed in the form of amino acids . (studysmarter.co.uk)
- BUPHENYL must be used with dietary protein restriction and, in some cases, essential amino acid supplementation. (horizonbyyourside.com)
- Ammonia the highly toxic product of protein catabolism, is rapidly inactivated by a variety of reactions. (medmuv.com)
- Reduced nitrogen enters the human body as dietary free amino acids, protein, and the ammonia produced by intestinal tract bacteria. (medmuv.com)
Accumulates3
- Occasionally, an individual may inherit a mild form of the disorder in which ammonia accumulates in the bloodstream only during periods of illness or other stress. (wikipedia.org)
- The excess nitrogen accumulates in the blood in the form of ammonia. (medlineplus.gov)
- 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)
Metabolism10
- published in Molecular Genetics and Metabolism Reports 3 , while nitrogen scavenging medications have been shown to be effective in helping to manage ammonia levels in some patients with UCDs, non-compliance with treatment is common. (biospace.com)
- 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)
- 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)
- In isovaleric acidemia, a lack of isovaleryl-CoA dehydrogenase, which is involved in the metabolism of the branched chain amino acid leucine, results in the inability to break down isovaleric acid and the accumulation of potentially toxic metabolites. (medicalhomeportal.org)
Toxic2
- Some patients may also have an elevation of ammonia, a toxic chemical, which can affect the nervous system. (wikipedia.org)
- Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. (medlineplus.gov)
Threonine1
- Aminotransferases exist for all amino acids except threonine and lysine. (medmuv.com)
Deficiency4
- BUPHENYL can be used in infants up to 28 days old who have a complete enzyme deficiency, and in patients 1 month of age and older who have a partial enzyme deficiency and have a history of brain damage from high blood levels of ammonia. (horizonbyyourside.com)
- Belonging to this class of disorders are those that involve complete deficiency (mut0) and partial deficiency (mut-) of the methylmalonyl-CoA mutase enzyme and other disorders causing excess methylmalonic acid excretion. (bvsalud.org)
- 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)
Enzyme2
- Overall, activity of the cycle is regulated by the rate of synthesis of N -acetylglutamate, the enzyme activator that initiates incorporation of ammonia into the cycle. (medscape.com)
- Pegvaliase, an injectable form of phenylalanine ammonia lyase, is an enzyme substitution therapy for adults with phenylketonuria (PKU). (bvsalud.org)
Elevation2
- A common clinical finding is mild-to-moderate blood ammonia elevation, which may contribute by direct neurotoxicity to changes in a patient's mentation. (medscape.com)
- Isolated" MMA refers to the presence of excess methylmalonic acid without homocysteine elevation. (bvsalud.org)
Supplementation1
- Some patients may also require individual branched-chain amino acid supplementation. (biospace.com)
Excess3
- The nervous system is especially sensitive to the effects of excess ammonia. (medlineplus.gov)
- Breaking down excess nitrogen and excreting it as urea prevents it from accumulating in the body as ammonia. (medlineplus.gov)
- Excreting the excess nitrogen prevents it from accumulating in the form of ammonia. (medlineplus.gov)
Alanine1
- In the liver, alanine transaminase transfers the ammonia to α-KG and regenerates pyruvate. (medmuv.com)
Dietary1
Renal2
- Renal impairment: monitor plasma ammonia levels at initiation. (empr.com)
- Defects of amino acid transport in the renal tubule include cystinuria and Hartnup disease, which are discussed elsewhere. (msdmanuals.com)
Incorporation1
- Ammonia incorporation in animals occurs through the actions of glutamate dehydrogenase and glutamine synthase. (medmuv.com)
Carbohydrate1
- 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)
Amino acid glutamine1
- 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)
Glutamine1
- 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)
Proteins5
- Our body digests and utilizes Proteins in the form of amino acids . (studysmarter.co.uk)
- It also synthesizes proteins and nitrogen-containing compounds like hormones and nucleotide bases using amino acids present in the body. (studysmarter.co.uk)
- Alongside Carbohydrates , fats, and Nucleic Acids , proteins are one of the Organic Molecules that make up most life forms. (studysmarter.co.uk)
- Proteins are amino acid chains connected by peptide bonds. (studysmarter.co.uk)
- Cellular amino acid pools are constantly being partially drained and refilled as the body synthesizes and degrades proteins. (studysmarter.co.uk)
Molecule1
- Each amino acid molecule has a central carbon C atom to which the amino and carboxyl groups are attached. (studysmarter.co.uk)
Levels6
- Elevated levels of argininosuccinic acid (5-110 μmol/L) in the plasma or urine are diagnostic. (wikipedia.org)
- I.V. nitrogen scavenging therapy (with sodium benzoate and/or sodium phenylacetate) should normalize ammonia levels, but if unsuccessful, hemodialysis is recommended. (wikipedia.org)
- Consider reducing dose if neurologic symptoms (eg, vomiting, nausea, headache, somnolence, confusion) occur in absence of high ammonia levels or other incurrent illness. (empr.com)
- Higher levels of phenylbutyrate (PBA) and phenylacetate (PAA), a conjugate base of phenylacetic acid, were observed when ACER-001 was administered under fasting versus fed conditions. (acertx.com)
- Laboratory changes are dyslipidemia, increased lactate-to-pyruvate ratio, higher levels of urinary oxidative stress markers, and considerable deviation in tricarboxylic acid (TCA) cycle metabolites. (nih.gov)
- This allows the levels of nitrogen in the body to decrease, reducing the amount of ammonia produced. (europa.eu)
Amide1
- 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)
Form1
- 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)