Alkaptonuria is a rare inherited genetic disease which is caused by a mutation in the HGD gene for the enzyme homogentisate 1,2-dioxygenase ; if a person inherits an abnormal copy from both parents, the body accumulates an intermediate substance called homogentisic acid in the blood and tissues. Homogentisic acid and its oxidized form alkapton are excreted in the urine, giving it an unusually dark color. The accumulating homogentisic acid causes damage to cartilage and heart valves, as well as precipitating as kidney stones and stones in other organs. Symptoms usually develop in people over 30 years old, although the dark discoloration of the urine is present from birth.
Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor of affected infants' urine, particularly prior to diagnosis and during times of acute illness.
Tyrosinemia or tyrosinaemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms of untreated tyrosinemia include liver and kidney disturbances. Without treatment, tyrosinemia leads to liver failure. Today, tyrosinemia is increasingly detected on newborn screening tests before any symptoms appear. With early and lifelong management involving a low-protein diet, special protein formula, and sometimes medication, people with tyrosinemia develop normally, are healthy, and live normal lives.
Pyruvate dehydrogenase deficiency is a rare neurodegenerative disorders associated with abnormal mitochondrial metabolism. PDCD is a genetic disease resulting from mutations in one of the components of the pyruvate dehydrogenase complex (PDC). The PDC is a multi-enzyme complex that plays a vital role as a key regulatory step in the central pathways of energy metabolism in the mitochondria. The disorder shows heterogeneous characteristics in both clinical presentation and biochemical abnormality.
Glycine encephalopathy is a rare autosomal recessive disorder of glycine metabolism. After phenylketonuria, glycine encephalopathy is the second most common disorder of amino acid metabolism. The disease is caused by defects in the glycine cleavage system, an enzyme responsible for glycine catabolism. There are several forms of the disease, with varying severity of symptoms and time of onset. The symptoms are exclusively neurological in nature, and clinically this disorder is characterized by abnormally high levels of the amino acid glycine in bodily fluids and tissues, especially the cerebrospinal fluid.
Homogentisic acid is a phenolic acid usually found in Arbutus unedo (strawberry-tree) honey. It is also present in the bacterial plant pathogen Xanthomonas campestris pv. phaseoli as well as in the yeast Yarrowia lipolytica where it is associated with the production of brown pigments. It is oxidatively dimerised to form hipposudoric acid, one of the main constituents of the 'blood sweat' of hippopotamuses.
4-Hydroxyphenylpyruvate dioxygenase (HPPD), also known as α-ketoisocaproate dioxygenase, is an Fe(II)-containing non-heme oxygenase that catalyzes the second reaction in the catabolism of tyrosine - the conversion of 4-hydroxyphenylpyruvate into homogentisate. HPPD also catalyzes the conversion of phenylpyruvate to 2-hydroxyphenylacetate and the conversion of α-ketoisocaproate to β-hydroxy β-methylbutyrate. HPPD is an enzyme that is found in nearly all aerobic forms of life.
Nitisinone, sold under the brand name Orfadin among others, is a medication used to slow the effects of hereditary tyrosinemia type 1 (HT-1).
Methylcrotonyl CoA carboxylase (MCC) is a biotin-requiring enzyme located in the mitochondria. MCC uses bicarbonate as a carboxyl group source to catalyze the carboxylation of a carbon adjacent to a carbonyl group performing the fourth step in processing leucine, an essential amino acid.
3-Hydroxy-3-methylglutaryl-CoA lyase is an enzyme that in human is encoded by the HMGCL gene located on chromosome 1. It is a key enzyme in ketogenesis. It is a ketogenic enzyme in the liver that catalyzes the formation of acetoacetate from HMG-CoA within the mitochondria. It also plays a prominent role in the catabolism of the amino acid leucine.
Homogentisate 1,2-dioxygenase (homogentisic acid oxidase, homogentisate oxidase, homogentisicase) is an enzyme which catalyzes the conversion of homogentisate to 4-maleylacetoacetate. Homogentisate 1,2-dioxygenase or HGD is involved in the catabolism of aromatic rings, more specifically in the breakdown of the amino acids tyrosine and phenylalanine. HGD appears in the metabolic pathway of tyrosine and phenylalanine degradation once the molecule homogentisate is produced. Homogentisate reacts with HGD to produce maleylacetoacetate, which then is further used in the metabolic pathway. HGD requires the use of Fe2+ and O2 in order to cleave the aromatic ring of homogentisate.
Methylmalonyl CoA epimerase is an enzyme involved in fatty acid catabolism that is encoded in human by the "MCEE" gene located on chromosome 2. It is routinely and incorrectly labeled as "methylmalonyl-CoA racemase". It is not a racemase because the CoA moiety has 5 other stereocenters.
Hypermethioninemia is an excess of the amino acid methionine, in the blood. This condition can occur when methionine is not broken down properly in the body.
4-Hydroxyphenylpyruvic acid (4-HPPA) is an intermediate in the metabolism of the amino acid phenylalanine. The aromatic side chain of phenylalanine is hydroxylated by the enzyme phenylalanine hydroxylase to form tyrosine. The conversion from tyrosine to 4-HPPA is in turn catalyzed by tyrosine aminotransferase. Additionally, 4-HPPA can be converted to homogentisic acid which is one of the precursors to ochronotic pigment.
Tyrosine aminotransferase is an enzyme present in the liver and catalyzes the conversion of tyrosine to 4-hydroxyphenylpyruvate.
Fumarylacetoacetase is an enzyme that in humans is encoded by the FAH gene located on chromosome 15. The FAH gene is thought to be involved in the catabolism of the amino acid phenylalanine in humans.
In enzymology, maleylacetoacetate isomerase is an enzyme that catalyzes the chemical reaction
Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial (MMSDH) is an enzyme that in humans is encoded by the ALDH6A1 gene.
3-Hydroxyisobutyryl-CoA deacylase deficiency is a rare autosomal recessive condition that is associated with severely delayed psychomotor development, neurodegeneration, increased lactic acid and brain lesions in the basal ganglia. Fewer than 10 patients have been described with this condition.
Tyrosinemia type I is a genetic disorder that disrupts the metabolism of the amino acid tyrosine, resulting in damage primarily to the liver along with the kidneys and peripheral nerves. The inability of cells to process tyrosine can lead to chronic liver damage ending in liver failure, as well as renal disease and rickets. Symptoms such as poor growth and enlarged liver are associated with the clinical presentation of the disease. Clinical manifestation of disease occurs typically within the first two years of life. The severity of the disease is correlated with the timing of onset of symptoms, earlier being more severe.
