Browsing Pathways

3-Methylcrotonyl-Coenzyme A Carboxylase Deficiency Type I also called 3-MCC Deficiency is a rare inborn error of metabolism (IEM) and is the result of defective pair of genes. More specifically defects in genes MCCC1 and MCCC2 cause 3-MCC Deficiency. 3-MCC has a very important role in protein metabolism in the body. In particular, the said enzyme is pivotal in one of the many steps which constitute the breakdown of leucine. Mutations in the aforementioned genes leads to a reduction in the activity of 3-MCC. As would naturally be expected, this causes the body to be unable to uptake and breakdown leucine properly. Consequently, this leads to the build up of toxic byproducts which are not processed as the breakdown of leucine is left incomplete. If these toxic byproducts manifest themselves in sufficiently high levels they can be very harmful, damaging the brain and nervous system. Symptoms include recurring episodes of vomiting and diarrhea, lethargy, hypotonia, seizures, and coma.

beta-Ketothiolase Deficiency (2-Methyl-3-Hydroxybutyric Acidemia; Mitochondrial Acetoacetyl-CoA Thiolase Deficiency; MAT Deficiency; T2 Deficiency; 3-KTD Deficiency; 3-Ketothiolase Deficiency) is an autosomal recessive disease caused by a mutation in the HADHB gene which codes for beta-ketathiolase. A deficiency in this enzyme results in accumulation of ammonia and ketone bodies in blood; and 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, 3-hydroxybutyric acid, tiglylglycine, and ketone bodies in urine. Symptoms include ketosis, seizures, organic acids in urine, and hyperammonemia. Treatment includes a low protein diet and L-carnitine.h3. h2.

Isovaleric acidemia (IVA) is caused by mutation in the isovaleryl CoA dehydrogenase gene. Isovaleryl CoA dehydrogenase is part of the acyl-CoA dehydrogenase family and is involved in the catabolism of leucine. A defect in this enzyme causes accumulation of ammonia, ketone bodies, Isovaleryl/2-Methylbutyrylcarnitine (C5) in blood; carnitine in plasma; creatinine, and glucose in serum; 3-Hydroxybutyric acid, 3-Hydroxyisovaleric acid, 4-Hydroxyvaleric acid, acetyltryptophan, glycine, acylcarnitin, isovalerylasparagine, isovalerylglycine, isovaleryllysine, isovalerylhistidine and isovaleryltryptophan in urine. Symptoms include encephalopathy, ketosis, metabolic acidosis, pancreatitis, sweaty feet odor, and thrombocytopenia.

Argatroban is a synthetic derivate of L-arginine and a direct thrombin inhibitor anticoagulant prescribed to patients with heparin-induced thrombocytopenia. Direct thrombin inhibitors bind plasma and fibrin bound thrombin independently of co-factor antithrombin.The inhibition of thrombin reduces the stability of the clot and promotes clot break down. Argatroban does not effect serine proteases like, trypsin, factor Xa, plasmin, and kallikrein. Argatroban is advantageous, particularly for renal failure patients, due to its short-half life and hepatic clearance.

Sterol 27-hydroxylase is a mitochondrial cytochrome P-450 species (CYP27) that catalyzes the first step in the degradation of steroid side chain in cholesterol to produce bile acids in the liver. When there are low concentrations of 27-Hydroxylase, patients will exhibit cerebrotendinous xanthomatosis, an autosomal recessive disorder characterized by the accumulation of cholestanol and cholesterol due to the inability to break down the lipids. The formation of xanthomas (deposits of lipids) in the nervous system and tendons will cause symptoms such as dementia, ataxia, and cataracts. Other symptoms may include damaged liver cells and body tissues.

Congenital Bile Acid Synthesis Defect Type II is a congenital defect in bile acid synthesis with delta(4)-3-oxosteroid 5-beta-reductase deficiency is caused by mutation in the AKR1D1 gene. 3-oxo-5-beta-steroid 4-dehydrogenase catalyzes the bile acid intermediates 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4-cholesten-3-one. Chenodeoxycholic acid and cholic acid are decreased in plasma and urine. Symptoms of this disease include cholestatic jaundice, atypical oxo and allo bile acids in urine and serum, liver failure, and steatosis.

Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation type, also known as methionine synthase deficiency or methylcobalamin deficiency, cblG type, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the methionine metabolim pathway. It is caused by a mutation in the MTR gene which encodes the enzyme methionine synthase. This enzyme is responsible for forming L-methionine and tetrahydrofolic acid from homocysteine and 5-methyltetrahydrofolic acid. When the enzyme is mutated, this leads to lower amounts of L-methionine in the cell, as well as increased levels of homocysteine. Methionine synthase deficiency is characterized by an increase in homocysteine levels in the body and excreted in the urine, as well as decreased levels of methionine in the blood. Symptoms include megaloblastic anemia, and can also include developmental delays, seisures and kidney failure. Treatment with vitamin B12, as well as folates and betaine is effective. It is estimated that methionine synthase deficiency affects less than 1 in 1,000,000 individuals.

Methylenetetrahydrofolate reductase deficiency (MTHFRD; Homocystinuria due to defect of n(5,10)-methylene THF deficiency) is caused by a defect in the MTHFR gene which codes for methylenetetrahydrofolate reductase. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. A defect in this enzyme results in accumulation of homocysteine and methionine in both plasma and urine. Some of the symptoms and signs include mental retardation, withdrawal, hallucinations, delusions, muscle weakness. Some patients remain asymptomatic until adulthood.

Phenylbutazone (also named fenilbutazona or butazolidin or bute) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to treat the pain and fever in animal. However, Phenylbutazone is not approved in United State and United Kingdom for human use anymore because of severe adverse effects. Phenylbutazone can block prostaglandin synthesis by the action of inhibition of prostaglandin G/H synthase 1 and 2. Prostaglandin G/H synthase 1 and 2 catalyze the arachidonic acid to prostaglandin G2, and also catalyze prostaglandin G2 to prostaglandin H2 in the metabolism pathway. Decreased prostaglandin synthesis in many animal model's cell is caused by presence of phenylbutazone.

Ornithine aminotransferase deficiency (OAT deficiency, ornithine keto acid aminotransferase deficiency, OKT deficiency, ornithine-delta-aminotransferase deficiency, gyrate atrophy of the choroid and retina) is an autosomal recessive disorder of ornithine metabolism caused by a defective ornithine aminotransferase (OAT). OAT catalyzes the conversion of ornithine into proline which is a conditionally essential amino acid. This disease is characterized by a very large accumulation of ornithine in the blood. Symptoms of the disease include tunnel vision, night blindness, myopia, and progressive vision loss.