Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Faced to the success of the neonatal screening for phenylketonuria and congenital hypothyroidism, it was tempting to introduce screening of other metabolic diseases. "Ideal" diseases to be screened are treatable, are not easily recognized by clinical means during the neonatal period, need immediate therapy to prevent irreversible disabilities, have a reasonable frequency and can be detected by and easy test. There is some controversy concerning the list of diseases recommended for mass screening, among them four can be discussed: congenital adrenal hyperplasia, due to 21-hydroxylase deficiency, fulfils most of the criteria, but some changes in the general screening strategy should be made to provide a result as soon as possible, and at least before the 10th day of life; cystic fibrosis, immunoreactive trypsin is a good marker of the disease but its assay needs technical adaptation for mass screening; more information are also required about the efficacy of an early management of the disease; Duchenne muscular dystrophy has a good marker for neonatal screening (creatine kinase), but no treatment exists and the possibility of genetic counselling can only be provided; hypercholesterolaemia is a frequent disease; however, the good marker and the adequate treatment remain to be defined. Pilot programmes, on the behalf of the French Association for Neonatal Screening, are evaluation these problems. However, at the present time, a consensus has been reached that only phenylketonuria and hypothyroidism fulfils criteria for an efficient mass screening programme.
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PMID:[Screening for hereditary diseases. What other screening?]. 317 79

Recently, attentions are being aroused as to the enzymatic network abnormalities lying behind congenital enzyme deficiency syndromes. We investigated abnormalities in activities of various hydrolytic enzymes in serum of patients with congenital adrenal hyperplasia (CAH, 21-hydroxylase deficiency). Several enzyme activities including trypsin-like enzyme, cathepsin C and esterase were significantly decreased in patients' serum. Especially the esterase activity in patients' serum was reduced to one third of controls and this may have some relations to the abnormal steroid metabolism of these patients. A multivariate analysis showed unexpectedly extensive abnormalities in enzyme interrelationships. These results suggest that wide variety of abnormal metabolism may be related to an apparent enzyme deficiency.
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PMID:Abnormalities of various serum enzyme activities in patients with congenital adrenal hyperplasia. 667 19

Steroidogenic acute regulatory protein (StAR) plays an essential role in steroidogenesis, facilitating delivery of cholesterol to cytochrome P450scc on the inner mitochondrial membrane. StAR is synthesized in the cytoplasm and is subsequently imported by mitochondria and processed to a mature form by cleavage of the NH2-terminal mitochondrial targeting sequence. To explore the mechanism of StAR action, we produced 6-histidine-tagged N-62 StAR (His-tag StAR) constructs lacking the NH2-terminal 62 amino acids that encode the mitochondrial targeting sequence and examined their steroidogenic activity in intact cells and on isolated mitochondria. His-tag StAR proteins stimulated pregnenolone synthesis to the same extent as wild-type StAR when expressed in COS-1 cells transfected with the cholesterol side-chain cleavage system. His-tag StAR was diffusely distributed in the cytoplasm of transfected COS-1 cells whereas wild-type StAR was localized to mitochondria. There was no evidence at the light or electron microscope levels for selective localization of His-tag StAR protein to mitochondrial membranes. In vitro import assays demonstrated that wild-type StAR preprotein was imported and processed to mature protein that was protected from subsequent trypsin treatment. In contrast, His-tag StAR was not imported and protein associated with mitochondria was sensitive to trypsin. Using metabolically labeled COS-1 cells transfected with wild-type or His-tag StAR constructs, we confirmed that wild-type StAR preprotein was imported and processed by mitochondria, whereas His-tag StAR remained largely cytosolic and unprocessed. To determine whether cytosolic factors are required for StAR action, we developed an assay system using washed mitochondria isolated from bovine corpora lutea and purified recombinant His-tag StAR proteins expressed in Escherichia coli. Recombinant His-tag StAR stimulated pregnenolone production in a dose- and time-dependent manner, functioning at nanomolar concentrations. A point mutant of StAR (A218V) that causes lipoid congenital adrenal hyperplasia was incorporated into the His-tag protein. This mutant was steroidogenically inactive in COS-1 cells and on isolated mitochondria. Our observations conclusively document that StAR acts on the outside of mitochondria, independent of mitochondrial import, and in the absence of cytosol. The ability to produce bioactive recombinant StAR protein paves the way for refined structural studies of StAR and StAR mutants.
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PMID:The mechanism of action of steroidogenic acute regulatory protein (StAR). StAR acts on the outside of mitochondria to stimulate steroidogenesis. 963 96