Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology最新文献

{"title":"Testosterone dehydrogenase activity in koala liver: characterisation of cofactor and steroid substrate differences","authors":"I. Stupans ,&nbsp;S. Kong ,&nbsp;A. Kirlich ,&nbsp;R.A. McKinnon ,&nbsp;M. Murray","doi":"10.1016/S0742-8413(99)00109-7","DOIUrl":"10.1016/S0742-8413(99)00109-7","url":null,"abstract":"<div><p>We have studied the hepatic microsomal 17β-hydroxysteroid dehydrogenase (17β-HSD) capacity of koala (<em>Phascolarctos cinereus)</em> and tammar wallaby (<em>Macropus eugenii</em>). A detailed comparison of the activity in hepatic fractions from koala and rat was made. Hepatic microsomal NADP-supported 17β-HSD activity was significantly higher in koala (11.64±3.35 nmoles/mg protein/min), (mean±S.D.) than in tammar wallaby liver (1.52±0.79 nmoles/mg protein/min). However, when NAD was utilised as cofactor the activity was similar in both marsupial species (2.83±2.03 nmoles/mg protein/min, koala; 0.70±0.71 nmoles/mg protein/min, tammar wallaby). Data for rat indicated a cofactor preference for NAD rather than NADP (17.94±6.40 nmoles/mg protein/min, NAD; 2.18±1.04 nmoles/mg protein/min, NADP). Michaelis–Menten parameters for the kinetics of 17β-HSD testosterone oxidation by NADP and NAD were determined in the koala. The Km for testosterone was of the order of 10.0–24.0 μM (<em>n</em>=6) irrespective of the cofactor used, whilst the Km for NADP was 0.28–0.43 μM (<em>n</em>=2) and for NAD was 13.9–18.5 μM (<em>n</em>=2). 17β-estradiol was found to be an inhibitor of both NAD- and NADP- supported 17β-HSD activity. These findings indicate that NADP-mediated, but not NAD-mediated testosterone dehydrogenation is a major pathway of steroid biotransformation in koala liver; the reaction is less extensive in fractions from wallaby, human and rat. Such species-related differences in cofactor preference may contribute along with species differences in gene expression to observed rates of 17β-HSD activity in mammals.</p></div>","PeriodicalId":10586,"journal":{"name":"Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0742-8413(99)00109-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77038280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basal lamina of avian ovarian follicle: influence on morphology of granulosa cells in-vitro","authors":"Elikplimi K Asem ,&nbsp;Shulin Feng ,&nbsp;Susan R Stingley-Salazar ,&nbsp;John J Turek ,&nbsp;Augustine T Peter ,&nbsp;J.Paul Robinson","doi":"10.1016/S0742-8413(99)00100-0","DOIUrl":"10.1016/S0742-8413(99)00100-0","url":null,"abstract":"<div><p>Experiments were conducted to determine the influence of basal lamina on the morphology of ovarian granulosa cells in vitro. Pure and intact basal lamina was isolated from the large preovulatory follicles of the chicken ovary and designated basal lamina of avian ovarian follicle (BLAOF). Examination of the isolated basal lamina with electron microscope revealed an ultrastructure that is similar to that of basal lamina in the intact ovarian follicle. Pieces of the intact basal lamina were attached to the bottom of 32 mm culture dishes (BLAOF-coated dishes) in which differentiated granulosa cells isolated from the largest preovulatory follicle or undifferentiated granulosa cells isolated from immature small yellow chicken ovarian follicles were cultured; uncoated dishes served as controls. Granulosa cells incubated on intact basal lamina assumed spherical shape, whereas granulosa cells incubated directly on plastic in control dishes became highly flattened. Interestingly, granulosa cells that attached to plastic close to BLAOF (in BLAOF-containing dishes) became rounded. The storage of BLAOF-coated culture dishes at 4°C for 2 years had no apparent effect on its ability of the matrix material to induce changes in granulosa cell shape. Some components of the basal lamina could be solubilized with guanidine–HCl alone (fraction 1; 90–95% of total protein in BLAOF) with the remaining components solubilized with β-mercaptoethanol containing guanidine–HCl (fraction 2; 5–10% of total protein in BLAOF). Differentiated and undifferentiated chicken granulosa cells became rounded when incubated in fraction 1-pre-coated wells; whereas those incubated directly on plastic in control wells were flattened. Similarly, when fraction 1 of solubilized basal lamina was added as liquid to incubation mixture, it caused both differentiated and undifferentiated granulosa cells to assume spherical shapes. The storage of fraction 1-coated culture dishes at 4°C for 12 or more months had no apparent effect on its ability to influence granulosa cell shape. Fraction 1-induced changes in granulosa cell shape were similar to those observed for complete and intact basal lamina (BLAOF). These findings demonstrate that intact homologous basal lamina (BLAOF) or its solubilized (fluidized) form can induce normal (in vivo) morphology in granulosa cells. It is suggested that BLAOF or its solubilized form can be used to culture cells in experiments designed to examine the influence of the natural basal lamina microenvironment on cellular behavior and function.</p></div>","PeriodicalId":10586,"journal":{"name":"Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0742-8413(99)00100-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86722738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathological changes in gills of the estuarine crab Chasmagnathus granulata (Crustacea-Decapoda) following acute exposure to ammonia","authors":"Mauro de Freitas Rebelo ,&nbsp;Enrique M. Rodriguez ,&nbsp;Euclydes A. Santos ,&nbsp;Martı́n Ansaldo","doi":"10.1016/S0742-8413(99)00093-6","DOIUrl":"10.1016/S0742-8413(99)00093-6","url":null,"abstract":"<div><p>Histopathological effects of ammonia on the gills of the estuarine crab <em>Chasmagnathus granulata</em> (Dana, 1851) were evaluated after acute exposure to ammonia concentrations around LC₅₀ value (17.85 Mm). Disruption of pilaster cells and a subsequent collapse of gill lamellae were the main effects observed. Ephitelial necrosis and hyperplasia were also detected. Significant (<em>P</em>&lt;0.05) increases in pCO₂ and lactate, and significant decreases of pO₂ were detected in the haemolymph of ammonia-exposed crabs. These changes suggest that the observed histopathological damage affected gas exchange, possibly leading to death.</p></div>","PeriodicalId":10586,"journal":{"name":"Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0742-8413(99)00093-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90793226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of basal lamina on progesterone production by chicken granulosa cells in vitro — influence of follicular development","authors":"Elikplimi K. Asem,&nbsp;Susan R. Stingley-Salazar,&nbsp;J.Paul Robinson,&nbsp;John J. Turek","doi":"10.1016/S0742-8413(99)00110-3","DOIUrl":"10.1016/S0742-8413(99)00110-3","url":null,"abstract":"<div><p>Experiments were conducted in vitro to study the regulation of progesterone production in chicken granulosa cells by homologous basal lamina isolated from preovulatory follicles of chicken ovary. The majority of components of the basal lamina (90–95% by weight) were solubilized with guanidine-HCl (and designated fraction 1); the remaining components were solubilized with β-mercaptoethanol containing guanidine-HCl (and designated fraction 2). The ability of fraction 1 to regulate progesterone production in granulosa cells obtained from the largest (F₁, mature), third largest (F₃, growing), fifth to seventh largest (F_5–7, growing) follicles and a pool of small yellow follicles (SYF, immature) of chicken ovary was assessed. Granulosa cells isolated from SYF follicles were in the least differentiated (undifferentiated) and those obtained from F₁ follicles were in the most differentiated state. The ability of fraction 1 to regulate progesterone production by chicken granulosa cells was influenced both by the state of cell differentiation and the form of the matrix material (whether solid or liquid). When fraction 1 was added as liquid to the incubation mixture, it promoted progesterone production by granulosa cells at all stages of differentiation; however, it caused a greater relative increase in the amount of progesterone produced by undifferentiated (SYF) and differentiating (F₃) granulosa cells than by differentiated (F₁) ones. In the presence of the liquid-form of fraction 1, luteinizing hormone (LH) stimulated progesterone production in differentiated (F₁) and differentiating (F_5–7) granulosa cells. Similarly, follicle-stimulating hormone (FSH) stimulated progesterone production by differentiating (F₃) and undifferentiated (SYF) granulosa cells in the presence of the liquid-form of fraction 1 protein. In culture wells that had been pre-coated with fraction 1 (solid-form), progesterone production by less differentiated (SYF, F_5–7) granulosa cells was enhanced, whereas progesterone production by differentiated (F₁) cells was reduced. The solid-form of fraction 1 augmented LH-stimulated progesterone production by less differentiated (F_5–7) granulosa cells however, it attenuated LH-induced progesterone production in differentiated (F₁) cells. FSH-promoted progesterone production in granulosa cells from immature follicles (SYF) was augmented by solid-form of fraction 1 whereas the effect of FSH on cells obtained from older follicle (F₃) was suppressed by solid-form of fraction 1. In experiments in which gonadotropin action was attenuated by solid-form of fraction 1, the amount of progesterone produced in the presence of maximally inhibiting concentrations of fraction 1 protein was greater than control values (no fraction 1, no gonadotropin). These results show that basal lamina of the ovaria","PeriodicalId":10586,"journal":{"name":"Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0742-8413(99)00110-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87967098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in mGnRH and cGnRH-II contents in pituitaries and discrete brain areas of Rana rugulosa W. according to age and stage of maturity","authors":"Li Yuanyou ,&nbsp;Lin Haoran","doi":"10.1016/S0742-8413(99)00099-7","DOIUrl":"10.1016/S0742-8413(99)00099-7","url":null,"abstract":"<div><p>(1) In tadpoles, chicken-II gonadotropin-releasing hormone (cGnRH-II) could be measured in the brains before metamorphosis, but mammalian gonadotropin-releasing hormone (mGnRH) did not appear until the stage of metamorphosis, i.e. cGnRH-II appeared earlier than mGnRH during ontogenesis. (2) During the metamorphic climax, mGnRH content increased more rapidly than cGnRH-II; the content of mGnRH was about two times of that of cGnRH-II. (3) In juveniles and adults, the content of mGnRH and cGnRH-II, and the distribution pattern of mGnRH (but not cGnRH-II) in the brains and pituitaries changed with age and stages of gonadal development. mGnRH mainly distributed in the rostral brain areas, whereas cGnRH-II had a widespread distribution in the brain. (4) Both mGnRH and cGnRH-II were present in the pituitaries at each stage of maturity. The gonadotropin-releasing hormone (GnRH) content at sexually maturity was significantly higher than that at other stages of gonadal development, and the content of mGnRH was about 15–18 times of that of cGnRH-II. (5) These results suggest that both mGnRH and cGnRH-II are potentially involved in the direct regulation of pituitary gonadotropes, and mGnRH may be the major active form, cGnRH-II may also serve as a neurotransmitter or neuromodulator in the brain.</p></div>","PeriodicalId":10586,"journal":{"name":"Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0742-8413(99)00099-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75946213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A thyrotropin-like molecule from the pituitary of an Indian freshwater murrel: comparison of its biological activity with other thyrotropins","authors":"Partha Roy ,&nbsp;Abhijit Chatterjee ,&nbsp;Partha Pratim Banerjee ,&nbsp;Samir Bhattacharya","doi":"10.1016/S0742-8413(99)00106-1","DOIUrl":"10.1016/S0742-8413(99)00106-1","url":null,"abstract":"<div><p>Murrel pituitary thyrotropin-like molecule (mTSH) was purified to homogeneity with the help of a convenient and sensitive in vitro assay system where addition of this material to the thyroid follicle incubation stimulated thyroxine (T₄) secretion into the medium. Pituitary extract of a freshwater murrel, <em>Channa punctatus</em>, was solvent extracted to obtain glycoprotein enriched fraction. This was subjected to Sephadex G-100 gel filtration and eluate of void volume (peak I) showed strong TSH activity (as reflected from T₄ secretion) which was further purified by using concanavalin A-Sepharose, FPLC Mono Q and immunoaffinity chromatography. Purified mTSH gave a single band in PAGE, and SDS PAGE revealed two dissimilar subunits, α and β. Addition of increasing concentrations of mTSH, Indian carp TSH (cTSH) and bovine TSH (bTSH) to in vitro murrel thyroid follicle incubations caused a linear increase in thyroxine (T₄) release into the medium, effect was highest with mTSH and lowest with bTSH. However, in in vivo experiments, injections of increasing doses of mTSH to murrel elevated plasma T₄ level in a linear manner while bTSH gave a biphasic response. Addition of mTSH and bTSH to rat or goat thyroid epithelial cell incubations equally stimulated T₄ release into the medium, while cTSH had significantly less effect. Binding affinity (<em>K</em>_a) and receptor occupancy (<em>B</em>_max) of mTSH to murrel thyroid follicular membrane preparation was considerably higher in comparison to cTSH or bTSH whereas both mTSH and bTSH had nearly similar <em>K</em>_a and <em>B</em>_max with rat thyroid epithelial cell membrane preparation. Findings indicate that mTSH is a more potent TSH as compared to carp and bovine TSH in murrel and has equipotent biological activity as bTSH on rat and goat thyroid.</p></div>","PeriodicalId":10586,"journal":{"name":"Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0742-8413(99)00106-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85326214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetylcholine/dopamine interaction in planaria","authors":"Francesca R Buttarelli ,&nbsp;Francesco E Pontieri ,&nbsp;Vito Margotta ,&nbsp;Guido Palladini","doi":"10.1016/S0742-8413(99)00111-5","DOIUrl":"10.1016/S0742-8413(99)00111-5","url":null,"abstract":"<div><p>Planaria represents the most primitive example of centralization and cephalization of nervous system. Previous reports indicate that planaria shows specific behavioral patterns, analogous to mammalian stereotypes, in response to drugs acting on acetylcholine or dopamine transmission. Here we further characterized these responses, and investigated the interactions between cholinergic and dopaminergic systems by means of behavioral methods. Exposure to cholinergic agonists physostigmine or nicotine produced hypokinesia with ‘bridge-like’ and ‘walnut’ positions, respectively. Blockade of muscarinic receptors by atropine produced ‘screw-like’ hyperkinesia. Exposure to dopamine agonists (nomifensine, apomorphine) produced marked hyperkinesia with ‘screw-like’ movements. Finally, exposure to dopamine antagonists produced immobility or ‘bridge-like’ position. Pre-exposure to physostigmine blocked the behavioral effects of nomifensine and reduced and markedly delayed the behavioral effects of apomorphine. Pre-exposure to apomorphine slightly reduced and delayed the behavioral changes by physostigmine. Finally, planaria exposed to atropine after either SCH23388 or sulpiride showed ‘C-like’ or ‘screw-like’ hyperkinesia, respectively. Thus, reduction of cholinergic transmission seems to play a pivotal role in determining hyperkinesia in planaria. Under these conditions, different patterns of hyperkinetic activities occur, according to the subpopulation of dopamine receptors stimulated by drugs. These findings suggest that interactions between cholinergic and dopaminergic systems occur very early in animal phylogeny.</p></div>","PeriodicalId":10586,"journal":{"name":"Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0742-8413(99)00111-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80434364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of β-adrenergic agonist L-644,969 on the impact of the thermal environment on in vitro fatty acid synthesis and lipogenic enzymes in sheep","authors":"Jacob A. Moibi,&nbsp;Robert J. Christopherson,&nbsp;Yuzhi Li","doi":"10.1016/S0742-8413(99)00108-5","DOIUrl":"10.1016/S0742-8413(99)00108-5","url":null,"abstract":"<div><p>The effect of temperature and β-adrenergic agonist (BAA) on in vitro rates of fatty acid synthesis and catalytic activity of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) was examined in wether lambs after 5 weeks at either 0 or 20°C. Feeding BAA increased (<em>P</em>&lt;0.05) rate of fatty acid synthesis by 38% in subcutaneous adipose (SC) tissue from cold-acclimated animals but the rate decreased (<em>P</em>&lt;0.05) by 27% in SC tissue from warm-acclimated animals. In mesenteric fat (MS), BAA increased (<em>P</em>&lt;0.05) fatty acid synthesis in the cold environment. In perirenal (PR) fat, rate of fatty acid synthesis was reduced (<em>P</em>&lt;0.05) by 20% by BAA in the warm but had no effect in the cold. Activity of ACC in longissimus muscle was depressed (<em>P</em>&lt;0.05) when BAA was fed in the warm environment. In adipose tissues BAA reduced (<em>P</em>&lt;0.05) ACC activity in the warm, but reduced activity in the cold was limited to SC tissue. In PR tissue FAS activity was reduced (<em>P</em>&lt;0.05) in the cold environment, while BAA increased FAS activity in the warm environment. Western blot analysis showed two isoforms of ACC with MW of 280 000 and 265 000 Da in longissimus muscle whereas only one isoform was recognized in each of Biceps femoris (280 000 Da) and adipose tissues (265 000 Da). Feeding BAA in the cold environment reduced (<em>P</em>&lt;0.05) ACC and FAS immunoprotein expression in both MS and PR adipose tissues. The studies indicate that the effect of BAA on fatty acid synthesis and lipogenic enzymes is influenced by acclimation temperature.</p></div>","PeriodicalId":10586,"journal":{"name":"Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0742-8413(99)00108-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80174567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclohexadienyl dehydrogenase from Pseudomonas stutzeri exemplifies a widespread type of tyrosine-pathway dehydrogenase in the TyrA protein family","authors":"Gary Xie ,&nbsp;Carol A. Bonner,&nbsp;Roy A. Jensen","doi":"10.1016/S0742-8413(99)00090-0","DOIUrl":"https://doi.org/10.1016/S0742-8413(99)00090-0","url":null,"abstract":"<div><p>The uni-domain cyclohexadienyl dehydrogenases are able to use the alternative intermediates of tyrosine biosynthesis, prephenate or <span>l</span>-arogenate, as substrates. Members of this TyrA protein family have been generally considered to fall into two classes: sensitive or insensitive to feedback inhibition by <span>l</span>-tyrosine. A gene (<em>tyrA</em>_c) encoding a cyclohexadienyl dehydrogenase from <em>Pseudomonas stutzeri</em> JM300 was cloned, sequenced, and expressed at a high level in <em>Escherichia coli</em>. This is the first molecular-genetic and biochemical characterization of a purified protein representing the feedback-sensitive type of cyclohexadienyl dehydrogenase. The catalytic-efficiency constant <em>k</em>_cat/<em>K</em>_m for prephenate (7.0×10⁷ M/s) was much better than that of <span>l</span>-arogenate (5.7×10⁶ M/s). TyrA_c was sensitive to feedback inhibition by either <span>l</span>-tyrosine or 4-hydroxyphenylpyruvate, competitively with respect to either prephenate or <span>l</span>-arogenate and non-competitively with respect to NAD⁺. A variety of related compounds were tested as inhibitors, and the minimal inhibitor structure was found to require only the aromatic ring and a hydroxyl substituent. Analysis by multiple alignment was used to compare 17 protein sequences representing TyrA family members having catalytic domains that are independent or fused to other catalytic domains, that exhibit broad substrate specificity or narrow substrate specificity, and that possess or lack sensitivity to endproduct inhibitors. We propose that the entire TyrA protein family lacks a discrete allosteric domain and that inhibitors act competitively at the catalytic site of different family members which exhibit individuality in the range and extent of molecules recognized as substrate or inhibitor.</p></div>","PeriodicalId":10586,"journal":{"name":"Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0742-8413(99)00090-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91727340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Who determines our trajectory beyond the year 2000 — you do","authors":"P.W Hochachka,&nbsp;T.P Mommsen","doi":"10.1016/S0742-8413(99)00121-8","DOIUrl":"https://doi.org/10.1016/S0742-8413(99)00121-8","url":null,"abstract":"","PeriodicalId":10586,"journal":{"name":"Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0742-8413(99)00121-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91726865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}