THE carboxy-terminal tetrapeptide of gastrin, Trp-Met-Asp-Phe-NH2, has the same biological activity as the parent hormone1. Morley2,3 showed that certain substitutions in the Trp, Met and Phe positions gave active analogues and concluded that these positions are concerned only with binding at the site of action. In contrast, the only substitution in aspartic acid that gave activity was tetrazolyl for the β-carboxyl, thereby maintaining a proton donor of similar size at this position. Morley concluded that the aspartyl residue has a functional rather than a binding role and presumably is indispensable. The carboxy-terminal octapeptide of cholecystokinin (OP-CCK) contains the carboxy-terminal tetrapeptide of gastrin and has gastrin-like activity4. We report here that the synthetic analogue of OP-CCK, in which alanyl is substituted for aspartyl at the position in question illustration, stimulates gastric acid secretion. In conscious cats with gastric fistulas5, dose-response curves were established for gastric acid response to OP-CCK, 7-Ala OP-CCK and pentagastrin6. The peptides were given by continuous intravenous infusion and response is taken as peak 10 min output during a 30 min infusion at each dose level (Fig. 1). Assigning a potency of 1 to OP-CCK the relative molar potency of 7-Ala OP-CCK is about 1/110 and of pentagastrin is about 1/4. We also tested the analogue of gastrin tetrapeptide in which alanyl is substituted for aspartyl illustration and found no detectable stimulation of acid secretion at doses as high as 15 mg/kg h, confirming similar negative findings by Morley2 in rat. This suggests that the weak action of alanyl substituted analogues cannot readily be detected without the enhancement of potency conferred by the sulphated tyrosyl of OP-CCK7. Ondetti et al.7 showed that 7-Ala OP-CCK contracts guinea-pig gallbladder with a potency about 1/150th that of OP-CCK, comparable with that reported here for acid secretion. This suggests that the same part or parts of the molecule are required for cholecystokinetic action and for gastric secretory action; the aspartyl residue in the penultimate position is dispensable for both of these actions. On the assumption that gastrin and CCK act at the same site8, we propose that the corresponding aspartyl residue of gastrin is similarly dispensable. For a direct test of this hypothesis, studies are needed of the synthetic analogue in which alanyl is substituted for the penultimate aspartyl in gastrin hepta-decapeptide, perferably gastrin II with sulphated tyrosyl because it is more potent than gastrin I in certain species9.
ABSTRACT. Horizontal gene transfer (HGT) and common descent interact in space and time. Because events of HGT co‐occur with phylogenetic evolution, it is difficult to depict evolutionary patterns graphically. Tree‐like representations of life's diversification are useful, but they ignore the significance of HGT in evolutionary history, particularly of unicellular organisms, ancestors of multicellular life. Here we integrate the reticulated‐tree model, ring of life, symbiogenesis whole‐organism model, and eliminative pattern pluralism to represent evolution. Using Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2), a bifunctional enzyme in the glycolytic pathway of amoeba, we illustrate how EhADH2 could be the product of both horizontally acquired features from ancestral prokaryotes (i.e. aldehyde dehydrogenase [ALDH] and alcohol dehydrogenase [ADH]), and subsequent functional integration of these enzymes into EhADH2, which is now inherited by amoeba via common descent. Natural selection has driven the evolution of EhADH2 active sites, which require specific amino acids (cysteine 252 in the ALDH domain; histidine 754 in the ADH domain), iron‐ and NAD+ as cofactors, and the substrates acetyl‐CoA for ALDH and acetaldehyde for ADH. Alternative views invoking “common design” (i.e. the non‐naturalistic emergence of major taxa independent from ancestry) to explain the interaction between horizontal and vertical evolution are unfounded. 相似文献
An antibiotic resistant staphylococcus with bacteriophage pattern 52/42B/80/81* is frequently responsible for infectious outbreaks in the newborn nursery. Some time after an outbreak had occurred in the University of California's hospital nursery, family members of the infants were found to be infected with this strain. Two families were studied in detail. In one of them, infection developed in six of the seven members within eight months after the infant's arrival. In the other, half of the family members had recurrent infections during a 13-month period.Infants who left the nursery as asymptomatic carriers were found as likely to transmit the infectious strain as those with clinical infection. Considerable time sometimes elapsed before infection developed in either the infant or the family members. In one instance the first familial infection occurred six months after the infant had left the nursery as an asymptomatic carrier. Newborn infants are quite likely to disseminate antibiotic resistant staphylococci which they may acquire from a hospital nursery. Infections developing among persons in contact with a young infant must be treated with the possibility of a resistant hospital staphylococcus in mind. 相似文献
