Browsing Pathways

Gamma-cystathionase deficiency, also called cystathionase deficiency, is an autosomal recessive metabolic disorder caused by a defective cystathionine gamma-lyase. Cystathionine gamma-lyase catalyzes the conversion of L-Serine and homocysteine into L-Cystathionine which is the substrate of cystathionine gamma-lyase. This disorder is characterized by a large accumulation of L-Cystathionine in the cell. Symptoms of the disorder include mental deficiency and seizure. Since there is currently no cure forGamma-cystathionase deficiency, treatment involves managing the disorder's symptoms.

Citrullinemia Type 1, also called argininosuccinate synthetase deficiency, argininosuccinic acid synthetase deficiency or ASS deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the urea cycle caused by a deficiency of argininosuccinate synthetase. Argininosuccinate synthetase is an important enzyme in the process of removing nitrogen from the body. This disorder is characterized by a large accumulation of ammonia in the blood as well as other bodily fluids . Symptoms of the disorder include vomiting, lethargy and intracranial pressure. Treatment with protein restriction and intravenous administration of arginine can help manage symptoms, and diet management throughout the patient’s life can also show improvement. It is estimated that citrullinemia type 1 affects 1 in 57,000 individuals.

Pyruvate carboxylase deficiency is caused by mutation in the pyruvate carboxylase gene. Serine—pyruvate aminotransferase catalyzes the reaction of serine and pyruvate to produce 3-hydroxypyruvate and L-alanine, as well as the reaction from L-alanine and glyodxylate to pyruvate and glycine. A defect in this results in accumulation of ammonia, glucose and pyruvate in blood; proline, lysine, citrulline, and alanine in plasma; and 2-oxoglutaric acid, fumaric acid, ketone bodies and succinate in urine. Symptoms include ataxia, lactic acidosis, mental retardation, metabolic acidosis, siezures, and dyspnea.

Joubert syndrome is a condition in which brain development is not completed as it should be, including the lack or underdevelopment of the part of the brain that regulates balance and coordination and an abnormal brain stem. The symptoms affect a variety of body parts in the patient, including apnea, ataxia brought on by hypotonia, abnormal eye movements and intellectual disability. Many different gene mutations are responsible for Joubert syndrome, all of the proteins created from these genes affecting the cilia that are found on the cell surface. It can be confirmed through its hallmark molar tooth imprint that shows up on brain scans of the patient, a visualization of the malformed brain stem and cerebellar vermis.

Cyclooxygenase is the major producer of prostacyclin. Prostacyclin binding to its receptor increases vasodilation and decreases platelet aggregation. The receptor is a G-protein coupled receptor, upon its binding it activates G proteins causing the activation of adenylyl cyclase and production of cAMP messenger molecules. cAMP activates PKA (protein kinase A) which phosphorylates downstream effectors that lead to a specific cellular response.In vasodilation, the PKA activity causes phosphorylation of MLCK, decreasing its activity, resulting in dephosphorylation of MLC of myosin. This leads to smooth muscle relaxation resulting in vasodilation.

Alkaptonuria (Homogentisic acid oxidase deficiency) is an autosomal recessive disease caused by a mutation in the HGD gene which codes for homogentisate 1,2-dioxygenase. A mutation in this enzyme results in accumulation of homogentisic acid in urine. Symptoms, which present in adulthood, include arthritis, black or brown urine, and urolithiasis. Treatment includes a low-protein diet with vitamin C.

BH4-deficient hyperphenylalaninemia has several causes. One such cause is a PTS deficiency resultant from a genetic mutation. (In particular, a mutation in the gene encoding 6-pyruvoyl-tetrahydropterin synthase.) The mutation is autosomal recessive. Common symptoms include: muscular hypotonia, ataxia, bradykinesia, choreoathetosis, depressivity, dysphagia, hyperkinesis, hypsarrhythmia, myoclonus, and others. BH4 is a cofactor involved in many things and associated with neurotransmitter synthesis. In short, the reduction of levels of BH4 creates issues in the metabolism of phenylalanine. This cascade of reactions produces the aforementioned symptoms.

Galactokinase deficiency also called Galactosemia type II, is a rare inborn error of metabolism (IEM) and an autosomal recessive disorder of galactokinase caused by a mutation in the GALK1 gene on chromosome 17q24. Galactokinase uses 1 ATP to catalyse the phosphorylation of α-D-galactose to galactose 1-phosphate and catalyses β-D-galactose to glucose 1-phosphate. Symptoms include cataract formation in children who are exposed to lactose in their diets. Cataract formation is the result of osmotic phenomena caused by the accumulation of galactitol in the lens. Treatment includes immediately removing lactose from patient’s diet, however symptoms such as delayed speech, cognitive learning and motor skills can still be present.

Fenoprofen (also named Nalfon) is a nonsteroidal anti-inflammatory drug. Fenoprofen 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 Fenoprofen.

Salicylate-sodium (also named salsonin or clin) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used for relieving pain and reducing fever. Salicylate-sodium 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 salicylate-sodium.