3-Methylglutaconic aciduria (MGA) is any of at least five metabolic disorders that impair the bodys ability to make energy in the mitochondria. As a result of this impairment, 3-methylglutaconic acid and 3-methylglutaric acid build up and can be detected in the urine. 3-Methylglutaconic acid is an organic acid. The double carboxylic acid functions are the principal cause of the strength of this acid. 3-methylglutaconic acid can be detected by the presence of the acid function and the double connection that involves reactivity with some specific substances. Genetics
The inheritance patterns of 3-methylglutaconic aciduria differ depending on the gene involved. Types I and III are inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder. Type II is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females.
The half-life of PTH is about 4 minutes.Disorders that yield too little or too much PTH, such as hypoparathyroidism, hyperparathyroidism, and paraneoplastic syndromes can cause bone disease, hypocalcemia, and hypercalcemia. Structure
hPTH-(1-84) crystallizes as a slightly bent, long, helical dimer. The extended helical conformation of hPTH-(1-84) is the likely bioactive conformation. The N-terminal fragment 1-34 of parathyroid hormone (PTH) has been crystallized and the structure has been refined to 0.9 Å resolution. Function
Regulation of serum calcium
Parathyroid hormone regulates serum calcium through its effects on bone, kidney, and the intestine:In bone, PTH enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL and inhibits their secretion of osteoprotegerin (OPG). Free OPG competitively binds to RANKL as a decoy receptor, preventing RANKL from interacting with RANK, a receptor for RANKL. The binding of RANKL to RANK (facilitated by the decreased amount of OPG available for binding the excess RANKL) stimulates osteoclast precursors, which are of a monocyte lineage, to fuse. The resulting multinucleated cells are osteoclasts, which ultimately mediate bone resorption. Estrogen also regulates this pathway through its effects on PTH. Estrogen suppresses T cell TNF production by regulating T cell differentiation and activity in the bone marrow, thymus, and peripheral lymphoid organs.