Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many children are born to women who consume drugs such as alcohol, cocaine, heroin, methadone, marijuana, and/or phencyclidine (PCP) during pregnancy. As a result, some children are growing up with both physical and developmental delays. Children with fetal alcohol syndrome have reported problems with growth, attention deficit disorder, and other medical problems. Impaired cognitive and neurologic functioning through the first 2 years of live has been documented for children exposed to methadone while in utero. Those children exposed to polydrug use including cocaine and marijuana seem to have difficulties with language development and verbal skills. Some of these deficiencies show improvement with early intervention and a nurturing environment, but in many cases the impairment continues throughout childhood. Because experimentation with drugs occurs at an early age, education related to drug prevention should begin early, possibly with school-aged children. Drug prevention education needs to be age and developmentally specific. The use of appropriate drug prevention strategies may help children make good decisions regarding drug use, especially during the teenage years when adolescent pregnancy may occur.
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PMID:Substance abuse: infant and childhood outcomes. 979 67

Here, I will review accumulating evidence that during the developmental period of synaptogenesis, also known as the brain growth spurt period, neurons are very sensitive to specific disturbances in their synaptic environment. During this period, abnormal increases in NMDA glutamate (Glu) receptor activity triggers excitotoxic neurodegeneration, and abnormal inhibition of neuronal activity (by blockade of NMDA Glu receptors or excessive activation of GABAA receptors) triggers neuronal suicide (apoptosis). Only a transient disturbance, lasting for a few hours, is sufficient to trigger either excitotoxic or apoptotic neurodegeneration during this developmental period. Ethanol, which has both NMDA antagonist and GABAmimetic properties, triggers widespread apoptotic neurodegeneration in the developing rat, mouse or guinea pig brain, and this provides a likely explanation for the reduced brain mass and lifelong neurobehavioral disturbances associated with the human fetal alcohol syndrome (FAS). The brain growth spurt occurs in different species at different times relative to birth. In rats and mice it is a postnatal event, but in humans it extends from the 6th month of gestation to several years after birth. Thus, there is a period in fetal and neonatal human development, lasting for several years, during which immature central nervous system (CNS) neurons are exquisitely sensitive to environmental agents (the specific number and variety of which remains to be established) that can trigger widespread neurodegeneration by inducing specific abnormal changes in the synaptic environment. Agents identified thus far include drugs that may be abused by pregnant mothers (ethanol, phencyclidine (PCP) (angel dust), ketamine (Special K), nitrous oxide (laughing gas), barbiturates, benzodiazepines) and many medicinals used in obstetric and pediatric medicine as sedatives, anti-convulsants or anesthetics (all general anesthetics are either NMDA antagonists or GABAmimetics). Many other chemicals in the human environment remain to be evaluated for their ability to cause developing CNS neurons to commit suicide, and this provides an exciting challenge for the field of developmental neurotoxicology.
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PMID:New insights and new issues in developmental neurotoxicology. 1252 Jul 55

Pneumocystis pneumonia or PCP is caused by Pneumocystis jirovecii, an obligate parasite of the human lung. In this study P. jirovecii genomic sequence encoding FAS, a trifunctional protein including dihydroneopterin aldolase (DHNA), hydroxymethyldihydropterin pyrophosphokinase (PPPK) and dihydropteroate synthase (DHPS) were identified by PCR amplification from fixed broncheolar lavage samples from patients having Pneumocystis pneumonia. The P. jirovecii trifunctional DHNA-PPPK-DHPS genes (PjFAS) showed a high degree of conservation with the rat Pneumocystis carinii and P. carinii f. sp. macaca sequences. To test the functionality of the PjFAS sequences introns were removed followed by cloning and expression of PjFAS sequences in a DHPS-disrupted Escherichia coli strain. Complementation depended on the presence of N-terminal FAS sequences in addition to a glutathione S- transferase tag to the N-terminus of PjFAS. Functional complementation allowed evaluation of DHPS mutations implicated with sulfa drug resistance.
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PMID:Cloning of the Pneumocystis jirovecii trifunctional FAS gene and complementation of its DHPS activity in Escherichia coli. 1553 Dec 10

Acyl (peptidyl) carrier protein (ACP or PCP) is a crucial component involved in the transfer of thiol ester-bound intermediates during the biosynthesis of primary and secondary metabolites such as fatty acids, polyketides, and nonribosomal peptides. Although many carrier protein three-dimensional structures have been determined, to date there is no model available for a fungal type I polyketide synthase ACP. Here we report the solution structure of the norsolorinic acid synthase (NSAS) holo ACP domain that has been excised from the full-length multifunctional enzyme. NSAS ACP shows similarities in three-dimensional structure with other type I and type II ACPs, consisting of a four-helix bundle with helices I, II, and IV arranged in parallel. The N-terminus of helix III, however, is unusually hydrophobic, and Phe1768 and Leu1770 pack well with the core of the protein. The result is that unlike other carrier proteins, helix III lies almost perpendicular to the three major helices. Helix III is well-defined by numerous NMR-derived distance restraints and may be less flexible than counterparts in type II FAS and PKS ACPs. When the holo ACP is derivatized with a hexanoyl group, only minor changes are observed between the HSQC spectra of the two ACP species and no NOEs are observed for this hydrophobic acyl group. Along with the mammalian type I FAS, this further strengthens the view that type I ACPs do not show any significant affinity for hydrophobic (nonpolar) chain assembly intermediates attached via the 4'-phosphopantetheine prosthetic group.
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PMID:Solution structure of an acyl carrier protein domain from a fungal type I polyketide synthase. 2013 99