The synthetic opioid alfentanil is an analgesic and an in vivo probe for hepatic and first-pass CYP3A activity. Alfentanil is a particularly useful CYP3A probe because pupil diameter change is a surrogate for plasma concentrations, thereby affording noninvasive assessment of CYP3A. Alfentanil undergoes extensive CYP3A4 metabolism via two major pathways, forming noralfentanil and N-phenylpropion...

The metabolic activation of estrone (E1), a potent estrogen was investigated using recombinant human cytochrome P450 enzymes, 1A2, 2B6, 2C8, 2C9, 2C9R144C, 2E1, 3A4, 3A5 and liver microsomes from 14 human organ donors. At least five products of E1 were detected and quantitated by HPLC and gas chromatography-mass spectrometry (GC-MS). Among these metabolites, 16alpha-OH-E1, 2-OH-E1 and 4-OH-E1, ...

The transport of newly synthesized proteins through the vacuolar protein sorting pathway in the budding yeast Saccharomyces cerevisiae requires two distinct target SNAP receptor (t-SNARE) proteins, Pep12p and Vam3p. Pep12p is localized to the pre-vacuolar endosome and its activity is required for transport of proteins from the Golgi to the vacuole through a well defined route, the carboxypeptid...

Newly synthesized vacuolar hydrolases such as carboxypeptidase Y (CPY) are sorted from the secretory pathway in the late-Golgi compartment and reach the vacuole after a distinct set of membrane-trafficking steps. Endocytosed proteins are also delivered to the vacuole. It has been proposed that these pathways converge at a "prevacuolar" step before delivery to the vacuole. One group of genes has...

PCR was used to isolate a carboxypeptidase Y (CPY) homolog gene from the fission yeast Schizosaccharomyces pombe. The cloned S. pombe cpy1+ gene has a single open reading frame, which encodes 950 amino acids with one potential N-glycosylation site. It appears to be synthesized as an inactive pre-pro protein that likely undergoes processing following translocation into appropriate intracellular ...

Mutations in the S. cerevisiae VPS29 and VPS30 genes lead to a selective protein sorting defect in which the vacuolar protein carboxypeptidase Y (CPY) is missorted and secreted from the cell, while other soluble vacuolar hydrolases like proteinase A (PrA) are delivered to the vacuole. This phenotype is similar to that seen in cells with mutations in the previously characterized VPS10 and VPS35 ...

BACKGROUND Multiple clinical, demographic, and genetic factors affect the pharmacokinetics of tacrolimus in children, yet in daily practice, a uniform body-weight based starting dose is used. It can take weeks to reach the target tacrolimus pre-dose concentration. OBJECTIVES The objectives of this study were to determine the pharmacokinetics of tacrolimus immediately after kidney transplantat...

A considerable number of fungal strains have developed resistant to various available antifungal agents due CPY, FKS and or ERG11 genes complicating coinfection cases SAR COV-2 virus. Therefore, this study sought isolate, identify azole polyene in pathogens isolated from confirmed SARS-CoV-2 individual Oyo State, Nigeria. Nasopharyngeal samples were collected symptomatic asymptomatic infected a...

Roughly 10 years ago, a small number of yeast labs isolated a collection of mutants that missort the enzyme carboxypeptidase Y (CPY) in an attempt to unravel vacuolar protein sorting, a process that is closely related to lysosomal enzyme sorting in mammals. They came up with an overwhelming number of VfS genes-more than 50 so far-and the screen is not saturated (see Stack et al., 1995b). How ca...