Browsing Pathways

Fc epsilon receptor 1 (Fc epsilon RI) is a high-affinity receptor for the Fc region of immunoglobulin E (IgE), an antibody isotope involved in allergies. The antigens of allergens bind to IgE antibodies, which then interact with Fc epsilon RIs on the surface of mast cells. This activates the mast cells and results in degranulation, a process by which preformed granules containing histamine, proteoglycans, and serine proteases, are released. Activated mast cells also synthesize and secrete lipid-derived mediators (such as prostaglandins, leukotrienes, and platelet-activating factor) and cytokines (notably tumor necrosis factor-alpha, interleukin-4, and interleukin-5). The release of these compounds results in the inflammatory response.

Xanthinuria Type II is a rare inborn error of metabolism (IEM) and autosomal recessive disorder and caused by a defective xanthine dehydrogenase. Xanthine dehydrogenase catalyzes the conversion of hypoxanthine into xanthine and conversion of xanthine into uric acid. This disorder is characterized by a large accumulation of xanthine and hypoxanthine; as well as dissipation of uric acid. Symptoms of the disorder include blood in the urine, recurrent urinary tract infections and abdominal pain. It is estimated that xanthinuria types I and II affects 1 in 69,000 individuals.

Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD), also called ACADL and VLCAD, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder, which is caused by a defective very long-chain specific acyl-CoA dehydrogenase. Very long-chain specific acyl-CoA dehydrogenase breakdown certain fats to energy. This disorder is characterized by a large accumulation of fatty acids such as L-Palmitoylcarnitine in the mitochondria. Symptoms of the disorder include muscle weakness, lethargy (lack of energy) and hypoglycemia (low blood sugar). Treatment with diet modifications such as consuming supplemental calories is suggested. It is estimated that very long-chain acyl-CoA dehydrogenase deficiency affects 1 in 40,000 to 120,000 individuals.

Glycogen storage disease type IV, also called GSD IV, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by a defective 1,4-alpha-glucan-branching enzyme. 1,4-alpha-glucan-branching enzyme catalyzes the conversion of amylose into glycogen which is essential component for cells to build up bodies. Symptoms of the disorder happen mainly in infants, which include failure to thrive, loss weight, enlarged liver and spleen, etc. Treatment with strict dietary therapy is effective in some cases. It is estimated that GSD IV affects 1 in 600,000 to 800,000 individuals worldwide.

Glycogen storage disease, also called glycogenosis and dextrinosis, is a rare inborn error of metabolism (IEM) and recessive disorder, which is caused by a defective glycogen synthase. Glycogen synthase catalyzes the conversion of uridine diphosphate glucose into amylose and uridine 5'-diphosphate which amylose is the substrate of 1,4-alpha-glucan-branching enzyme and glycogen debranching enzyme. This disorder is characterized by a large accumulation of glycogen in the liver or muscles. Symptoms of the disorder depends on the type of glycogen storage disease (e.g. GSD I, GSD III, etc.). Treatments are also depend on the type of glycogen storage disease.

Teniposide is a type of chemotherapy drug, derived from the epipodophyllotoxin form the American Mayapple plant. Teniposide is related to etoposide, another anti-cancer drug. It works in a similar way, inhibiting topoisomerase II. This causes single- and double-stranded DNA breaks. These breaks cause cell growth to stop and prevents cancer cells from entering mitosis. It is administered through an intravenous infusion. It is used to treat many cancers such as lymphoma, leukemia (acute lymphocytic), and neuroblastoma.

Enoxaparin is a low molecular weight heparin used to reduce cardiovascular events. Enoxaparin's action is antithrombin-dependent. The drug binds to antithrombin III to reduce thrombin inhibition in the plasma. The drug increases the inactivation of coagulation factors IXa, Xa and XIIa. This increases the antithrombin effects. Compared to unfractionated heparin, low molecular weight heparins have lower affinity for plasma proteins and therefore only few are protein bound. They also are not inactivated by platelet factor 4 and does not bind endothelial cells or macrophages thus are not degraded as fast. Therefore, low molecular weight heparins like Enoxaparin are more stable and predictable heparins.

Bivalirudin, trade name angiomax, is a direct thrombin inhibitor. It is often prescribed to patients who cannot take unfractionated or low molecular weight heparin. Bivalirudin does not need cofactor antithrobin to act. It binds circulating and clot-bound thrombin at the catalytic site and the anion binding exosite. The inhibition of fibrin prevents the cleavage of fibrinogen into fibrin which activates Factor XIII and Factor XIIIa. This destabilizes the thrombus and inhibits the promotion of thrombin production and platelet activation. As a result, bivalirudin prevents or reduces clot formation.

Corticosterone methyloxidase type II (CMO-II) deficiency, also called 18-oxidase defiency or aldosterone deficiency II among other names, is a genetic disorder that is autosomally linked. It is caused by a mutation in the cytochrome P450 11B2 gene, whose protein product is responsible for the formation of aldosterone from 18-hydroxycorticosterone (18-OHB), as well as converting progesterone to 11b-hydroxyprogesterone. The conversion of 18-OHB to aldosterone is the only reaction that uses 18-OHB, and due to the enzyme not being entirely functional, it builds up in the cell, while aldosterone levels will be lowered. However, since progesterone and 11b-hydroxyprogesterone are both produced and used by other reactions, their levels in the cell are not changed as drastically. Compared to the CMO-I deficiency, the CMO-II deficiency has less severe mutations in the gene, which cause it to have less severe changes in aldosterone and 18-OHB concentrations. The CMO-II deficiency, and its resulting aldosterone deficiency can cause a salt-wasting phenotype in children, due to aldosterone being responsible for the resorption of sodium in the body, as well as secretion of potassium. With levels of aldosterone being lower due to this deficiency, excess sodium is excreted in the urine, and higher than average levels of potassium in the serum. Aside salt-wasting and potential failure to thrive as an infant due to this, there are no symptoms, such as genital abnormalities, that are seen in similar salt-wasting disorders like CYP21 deficiency.

Adrenal hyperplasia type 5 (AH5) also known as Congenital Adrenal Hyperplasia Due to 17 alpha-Hydroxylase Deficiency is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of cortisol and sex steroids synthesis caused by a defect in the CYP17A1 gene which codes for Steroid 17-alpha-hydroxylase/17,20 lyase. These 2 enzymes catalyze pregnenolone and progesterone to their 17-hydroxy forms in steroidogenesis and mediate three key transformations in cortisol and sex steroid synthesis. This disorder is characterized by a decrease in both cortisol and sex steroids and increase in mineralocorticoids. Symptoms of the disorder include mild hypocortisolism, ambiguous genitalia in genetic males or failure of the ovaries to function at puberty in genetic females, and hypertension. Treatments for Hypertension and mineralocorticoid excess is done with glucocorticoid replacement. Genetically female patients need female hormone replacement to induce puberty and regulate menses. Surgery may be needed for males with ambiguous genitalia. Testosterone must be replaced for genetically males (XY) to induce puberty and continued throughout adult life. It is estimated that Adrenal hyperplasia type 5 affects 1 in 1 million individuals worldwide.