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1.
Arch Androl ; 44(2): 93-101, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10746865

RESUMO

Progesterone (P) and zona pellucida are known to induce acrosome reaction in human sperm by increasing cytosolic calcium. High concentrations of potassium ions (K+) improve the rate of acrosome reaction in human sperm in vitro. This article determined whether the effect of K+ on the acrosome in human sperm is mediated by increasing intracellular calcium ([Ca2+]i). The effect of K+ on [Ca2+]i was examined by using Fura 2 as the fluorescent indicator. The effect of K+ and P on [Ca2+]i in sperm and the involvement of ion channels was compared. Motile sperm were collected by the swim-up method from semen of healthy volunteers and capacitated overnight in BWW containing 0.5% BSA. Incubation of capacitated sperm with different concentrations of potassium chloride (1.25-20 mM) resulted in dose-dependent increase in [Ca2+]i similar to that observed with P. The increase in [Ca2+]i by K+ and P was blocked by the addition of EGTA, a Ca2+ chelator. K+-induced change in [Ca2+] was not altered by the addition of dihydropyridine derivatives. The combined treatment of K+ (20 mM) and P (0.75 microg/mL) caused an additive effect on the increase in [Ca2+]i. It would appear that human sperm plasma membrane possess different Ca2+ channels responsive to P and K+.


Assuntos
Cálcio/metabolismo , Potássio/fisiologia , Espermatozoides/metabolismo , Cálcio/antagonistas & inibidores , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Humanos , Técnicas In Vitro , Masculino , Progesterona/metabolismo , Capacitação Espermática , Zona Pelúcida/fisiologia
2.
Clin Sci (Lond) ; 87(5): 499-503, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7874836

RESUMO

1. Earlier studies with liver slices showed that inhibition by NH4+ of the oxidation of palmitate to CO2 was greater than total oxidation, whereas salicylate exerted a stronger inhibitory effect on the latter. We have now investigated the effects of NH4Cl and salicylate on ADP-induced O2 consumption by mitochondria (State 3 rate) respiring on pyruvate, and oxidation of [1-14C]- and [2-14C]-pyruvate to 14CO2. 2. The rate of State 3 respiration was inhibited and plateaued at 45% with 10 mmol/l NH4Cl. 3. Oxidation of [1-14C]pyruvate was not significantly affected by either NH4Cl or salicylate. Oxidation of [2-14C]pyruvate was strongly inhibited and plateaued at 70% with 1 mmol/l NH4Cl (IC50 = 0.125 mmol/l). ADP (1 mmol/l) increased the rate of decarboxylation of [2-14C]pyruvate but the extent of NH4Cl inhibition was not affected. Salicylate had a slight activating effect in the absence or presence of NH4Cl. 4. These results indicate that NH4Cl inhibits the oxidative metabolism of acetyl-CoA in the tricarboxylic acid cycle. Therefore, inhibition of fatty acid oxidation to acetyl-CoA as well as its further oxidative metabolism occurring under hyperammonaemia (> 0.1 mmol-1.49 mmol/l in Reye's syndrome patients) may be one of the causes of fatty acidaemia. 5. The cumulative inhibitory effects of NH4+ and fatty acyl derivatives on mitochondrial oxidative metabolism and production of ATP, as well as the uncoupling effects of salicylate, may contribute to some of the pathophysiology observed in patients with Reye's syndrome, and enzyme defects of the urea cycle.


Assuntos
Cloreto de Amônio/farmacologia , Fígado Gorduroso/etiologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Piruvatos/metabolismo , Síndrome de Reye/metabolismo , Difosfato de Adenosina/metabolismo , Animais , Dióxido de Carbono/metabolismo , Relação Dose-Resposta a Droga , Masculino , Mitocôndrias Hepáticas/metabolismo , Oxirredução/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Ácido Pirúvico , Ratos , Ratos Sprague-Dawley , Salicilatos/farmacologia , Ácido Salicílico , Ureia/metabolismo
3.
Cell Calcium ; 15(5): 349-55, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8033193

RESUMO

Regulation of steroidogenesis by luteinizing hormone is mediated by cAMP and calcium. We have investigated changes in cytosolic free calcium ([Ca2+]i) in Leydig cells by using Fura-2 as the fluorescent calcium indicator. Purified Leydig cells were plated on polylysine coated glass coverslips, cultured for 24 h in DMEM/F12 and loaded with Fura-2 at 37 degrees C. [Ca2+]i measurements were made fluorometrically by placing coverslips into 3 ml cuvettes with PBS+calcium. Addition of hCG increased [Ca2+]i gradually after a lag of about 2-3 min and plateaued by 5-6 min. The plateau level was sustained for at least 15 min. Absence of external Ca2+ in the medium or presence of diltiazem or nicardipine or cobalt chloride abolished the rise. Addition of BAY K 8644 or KCl caused a small but significant increase of [Ca2+]i. 8-Br-cAMP, forskolin or cholera toxin produced a gradual rise in [Ca2+]i that plateaued after 5-6 min similar to that observed with hCG. The action of hCG was inhibited by protein kinase A inhibitor (20-residues peptide) but not by protein kinase C inhibitor (staurosporine). We conclude that binding of hCG to its receptors would transmit the signal through G proteins to adenylyl cyclase to increase cAMP which would increase Ca2+ influx into cytosol across plasma membrane Ca2+ channels. Therefore, it appears that the primary action of hCG is to increase cytosolic cAMP which would then regulate [Ca2+]i as well as steroidogenesis.


Assuntos
Cálcio/metabolismo , Gonadotropina Coriônica/farmacologia , Células Intersticiais do Testículo/efeitos dos fármacos , Animais , AMP Cíclico/metabolismo , Técnicas In Vitro , Masculino , Ratos , Ratos Sprague-Dawley
4.
J Bioenerg Biomembr ; 25(4): 419-27, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7693659

RESUMO

Phosphate and a number of other compounds induce membrane permeability transition (MBT) in Ca(2+)-loaded mitochondria. 1-Anilino-8-naphthalene sulfonate (ANS) was used as a fluorescent probe to investigate perturbations on the inner membrane during MBT. Induction of MBT caused ANS fluorescence enhancement with a biphasic rate that reached a plateau. The enhancement is analogous to that reported for de-energization of mitochondria. The fluorescence level was independent of whether ANS was added before or at different times after phosphate. In the absence of ANS, fluorescence was low and remained unchanged. The initial time course of MBT, as followed by large-amplitude swelling, was similar to that of fluorescence enhancement. Ruthenium red, EGTA, ADP, and cyclosporin A inhibited the enhancement. Only EGTA + ADP (or ATP) reversed the enhancement when added after phosphate. Efflux of matrix Ca2+ by sodium acetate or A23187 did not alter ANS fluorescence. The binding parameters (Kd and number of binding sites) were not significantly different, but the fluorescence maximum was more than doubled after MBT. Although the fluorescence of bound ANS showed a nonlinear relationship, it was always higher (73.0 +/- 19.0%) after reaching the plateau. Since ANS binding to membranes is nonspecific, the exact mechanism of the enhanced fluorescence is not apparent. The dependence of the initial rate of fluorescence enhancement on Ca2+ concentration was nonlinear, with 45 microM at half-maximal rate. The dependence on phosphate was hyperbolic with 0.7 mM at half-maximal rate, which is close to the Km value of phosphate carrier. The kinetics is compatible with Ca2+ binding to some membrane component(s) during MBT and cause ANS fluorescence enhancement.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Naftalenossulfonato de Anilina/química , Cálcio/fisiologia , Corantes Fluorescentes/química , Membranas Intracelulares/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Fosfatos/farmacologia , Acetatos/farmacologia , Ácido Acético , Difosfato de Adenosina/farmacologia , Animais , Calcimicina/farmacologia , Ciclosporina/farmacologia , Ácido Egtázico/farmacologia , Fluorescência , Masculino , Potenciais da Membrana , Mitocôndrias Hepáticas/química , Concentração Osmolar , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Rutênio Vermelho/farmacologia
5.
FASEB J ; 4(5): 1513-8, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2307329

RESUMO

The temporal relationship of changes in state 3 respiration, lipid peroxidation, and glutathione (GSH) content was investigated in liver mitochondria of hypophysectomized rats after an injection of 3,3',5-triiodo-L-thyronine (T3). Lipid peroxidation induced by ADP/Fe3+/NADPH was determined by the amount of malondialdehyde formed. Hypophysectomy decreased respiration and lipid peroxidation (from 19.88 +/- 3.04 to 14.19 +/- 1.14 nmol malondialdehyde.mg protein-1.10 min-1) but increased GSH content (from 7.06 +/- 2.08 to 12.46 +/- 3.58 nmol/mg protein). Daily injections of a low dose (5 micrograms/100 g) of T3 for 7 days restored the parameters. Time course (up to 96 h) of these changes was followed after one injection of a moderate (100 micrograms/100 g) and high (1000 micrograms/100 g) dose of the hormone. Respiration showed a significant increase at 24 h and declined slightly at 96 h. There was a slow loss of respiratory control ratio after 24 h. Lipid peroxidation remained unchanged at 24 h and showed a gradual increase, becoming significantly higher at 72-96 h depending on the hormone dosage. Changes in GSH content followed a time course similar to that of lipid peroxidation except that it showed a decrease instead of an increase. There was a high degree of inverse linear correlation between lipid peroxidation and GSH (correlation coefficient = 0.95). Because GSH is required for detoxification of hydroperoxides generated by the respiratory chain, it is suggested that lipid peroxidation may play a major role in the modulation of intramitochondrial GSH.


Assuntos
Glutationa/fisiologia , Peroxidação de Lipídeos/fisiologia , Mitocôndrias Hepáticas/metabolismo , Consumo de Oxigênio/fisiologia , Animais , Hipofisectomia , Masculino , Malondialdeído/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Tri-Iodotironina/farmacologia
6.
Pediatr Res ; 25(2): 119-23, 1989 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2919125

RESUMO

To explore the possible association of hyperlipidemia with hyperammonemia and aspirin ingestion, the effects of NH4+, salicylate, and carnitine on the oxidation of [1-14C]palmitic acid to acid-soluble products (ASP) and to CO2 were investigated in rat liver slices. DL-carnitine (5 mM) increased total oxidation (ASP + CO2) more than oxidation to CO2. KCN (1.5 mM) inhibited more than 90% of the oxidation. NH4Cl inhibited the oxidation that reached a maximum at about 40 mM, but the inhibition of oxidation to CO2 (63%) was larger than that of total oxidation (30%). Carnitine did not influence NH4+ inhibition, which is consistent with the results reported for isolated mitochondria. Salicylate effects depended on salicylate concentration as well as on the presence of carnitine. In the absence of carnitine, inhibition of total oxidation reached 90% at 3 mM salicylate but that of oxidation to CO2 reached 50%. Velocity calculated at saturating palmitic acid concentration for total oxidation was slightly increased by 0.75 mM salicylate, but the increase for oxidation to CO2 was larger. At 3 mM salicylate, velocity at saturating palmitic acid concentration for the oxidation was decreased, but the decrease for oxidation to CO2 was smaller than for total oxidation. Carnitine partially relieved the inhibition of total oxidation and further increased the formation of CO2. The combination of 20 mM NH4Cl and 0.75 mM salicylate inhibited total oxidation, which was more than additive of the individual effects, and carnitine partially relieved the inhibition. It is concluded that NH4+ exerted a stronger inhibition of oxidation to CO2 than of oxidation to ASP, whereas salicylate strongly inhibited the oxidation to ASP but increased the oxidation to CO2 by uncoupling mitochondrial oxidative phosphorylation. Therefore, hyperammonemia and aspirin ingestion can inhibit fatty acid oxidation and mitochondrial metabolism that could lead to the pathophysiology seen in some childhood diseases such as Reye's syndrome. Carnitine therapy might offer some benefits.


Assuntos
Cloreto de Amônio/farmacologia , Carnitina/farmacologia , Fígado/metabolismo , Ácidos Palmíticos/metabolismo , Salicilatos/farmacologia , Animais , Técnicas In Vitro , Fígado/efeitos dos fármacos , Masculino , Oxirredução , Ácido Palmítico , Ratos , Ratos Endogâmicos , Ácido Salicílico
7.
Arch Biochem Biophys ; 260(1): 359-76, 1988 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3341749

RESUMO

In order to investigate the effects of growth and thyroid hormones on Ca2+ transport in liver mitochondria, Ca2+ release and other accompanying changes induced by t-butylhydroperoxide were measured in mitochondria from hypophysectomized and hormone-injected rats. Mitochondria from normal and hypophysectomized rats showed similar rates of Ca2+ uptake (40 nmol.min.-1 mg protein-1) and ruthenium red-insensitive release (3 nmol.min.-1 mg protein-1). However, the t-butylhydroperoxide (0.5 mM)-induced release of 90% of the added Ca2+ required 1027 +/- 98 and 560 +/- 35 s in the hypophysectomized and normal groups, respectively, and the difference was independent of Ca2+. The release was accompanied by a loss of membrane potential, large amplitude swelling, the oxidation of NAD(P)H and stimulation of respiration. At conditions of equivalent release rates, the rate and extent of swelling as well as the stimulation of respiration were lower in mitochondria from hypophysectomized rats than those in the normal group. These results were confirmed by electron microscopy and provided evidence for a dissociation between the release of Ca2+ and the increase of membrane permeability. The administration of bovine growth hormone and/or 3,5,3'-triiodo-L-thyronine to hypophysectomized rats decreased the Ca2+ release times by different degrees and thyroid hormone was more effective than growth hormone. Hypophysectomy doubled the GSH content and hormone injections decreased it and the Ca2+ release times in parallel. Indeed, a high degree of correlation (r = 0.96) was obtained between mitochondrial GSH and the release times from groups of differing hormone status. Differences in the groups in the time required for oxidation of 80-90% of GSH were correlated with the differences in the times for release of 90% Ca2+. Therefore, these results demonstrated that growth and thyroid hormones can alter both the hydroperoxide-induced Ca2+ release and the metabolism of GSH in liver mitochondria, suggesting that the two processes are related. It is proposed that the effects of these hormones on Ca2+ transport may result from the promotion of its efflux from mitochondria and its mobilization into the cytosol.


Assuntos
Cálcio/metabolismo , Glutationa/metabolismo , Hormônio do Crescimento/farmacologia , Hipofisectomia , Mitocôndrias Hepáticas/metabolismo , Peróxidos/farmacologia , Tri-Iodotironina/farmacologia , Animais , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Masculino , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias Hepáticas/enzimologia , Mitocôndrias Hepáticas/ultraestrutura , Dilatação Mitocondrial/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Nucleotídeos de Pirimidina/metabolismo , Ratos , Ratos Endogâmicos
8.
Lipids ; 21(11): 677-83, 1986 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3796232

RESUMO

Effects of growth hormone on phospholipid composition and fatty acyl distribution were studied in liver mitochondria of hypophysectomized rats. After hypophysectomy, only cardiolipin showed a 25% decrease. Its fatty acyl distribution, which consisted mainly of linoleic acid (55-60%) and oleic acid (20%), was unchanged. In phosphatidylcholine and phosphatidylethanolamine fractions the contents of docosahexaenoic and arachidonic acids were decreased with a concomitant increase in linoleic acid content. These changes could be accounted for by small but significant decreases in the activities of delta 9-desaturase (sucrose-induced), delta 5-desaturase and mitochondrial elongation enzymes. The activities of delta 6-desaturase, NADH cytochrome b5 ferri-reductase, cytochrome b5, NADH cytochrome c reductase and microsomal elongation enzymes remained virtually unchanged. Injection of bovine growth hormone daily for seven days restored cardiolipin and fatty acyl distribution and the enzyme activities. From these and other results, we conclude that growth hormone-dependent increase of respiratory activity of liver mitochondria may be partly mediated by the hormonal effects on membrane lipid distribution.


Assuntos
Ácidos Graxos/metabolismo , Hormônio do Crescimento/farmacologia , Membranas Intracelulares/metabolismo , Lipídeos de Membrana/metabolismo , Mitocôndrias Hepáticas/metabolismo , Fosfolipídeos/metabolismo , Animais , Colesterol/metabolismo , Hipofisectomia , Membranas Intracelulares/efeitos dos fármacos , Cinética , Masculino , Mitocôndrias Hepáticas/efeitos dos fármacos , Fosfatidilcolinas/metabolismo , Ratos , Ratos Endogâmicos
9.
Endocrinology ; 119(1): 250-2, 1986 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2941269

RESUMO

The time course of the effects of GH on state 3 respiration and fatty acid composition of liver mitochondria was investigated up to 48 h after an injection of bovine GH to hypophysectomized rats. The respiratory rate increased significantly by 12 h, whereas the docosahexaenoic acid level, the total unsaturation index, and the ratio of arachidonic acid to linoleic acid of total phospholipids increased as early as 4 h after the hormone injection. A linear association was found between the respiratory rate and the three measures of fatty acid composition. It is concluded that the hormonal effects on respiration may be partly mediated through changes in fatty acid composition, which have an additive effect on increased synthesis of proteins and respiratory chain components.


Assuntos
Ácidos Graxos/análise , Hormônio do Crescimento/farmacologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Fosfolipídeos/análise , Animais , Ácido Araquidônico , Ácidos Araquidônicos/análise , Bovinos , Ácidos Docosa-Hexaenoicos , Ácidos Graxos Insaturados/análise , Ácido Linoleico , Ácidos Linoleicos/análise , Masculino , Microssomos Hepáticos/análise , Mitocôndrias Hepáticas/metabolismo , Ratos , Ratos Endogâmicos , Estimulação Química
10.
Biochem Biophys Res Commun ; 127(2): 565-70, 1985 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-3977937

RESUMO

NH4C1 inhibited oxygen consumption (State 3, ADP induced) by rat liver mitochondria respiring on palmitoyl-L-carnitine or octanoic acid but not on succinate or malate + glutamate. The inhibition became apparent at 0.02 mM reaching a plateau (40%) at 2 mM NH4C1. Similar inhibition was observed with uncoupled (in the presence of 2, 4-dinitrophenol) mitochondria. The inhibition of uncoupled mitochondria was reversible as the rate of respiration with palmitoyl-L-carnitine was further increased by succinate and the total rate was unaffected by NH4C1. Therefore, NH+4 inhibition of mitochondrial respiration may lead to fatty infiltration and be one of the causes of the pathophysiology in children with Reye's syndrome and disorders of urea cycle enzymes.


Assuntos
Cloreto de Amônio/farmacologia , Ácidos Graxos/metabolismo , Mitocôndrias Hepáticas/metabolismo , Síndrome de Reye/metabolismo , Ureia/metabolismo , Animais , Técnicas In Vitro , Masculino , Oxirredução/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Endogâmicos
11.
Pediatr Ann ; 13(7): 565-72, 1984 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6472907

RESUMO

Most of the energy required for muscle contraction is generated by the splitting of ATP. Catabolism of carbohydrates to pyruvate and lactate by glycolysis (anaerobic) produces ATP needed during exercise of high intensity and short duration but the energy release is incomplete. The first step in the release of the remaining energy is the conversion of pyruvate to acetyl-CoA which is also formed from the oxidation of fatty acids particularly during sustained exercise. Acetyl-CoA is next oxidized in the tricarboxylic acid cycle producing the reduced forms of pyridine and flavin nucleotides. The hydrogens of the reduced nucleotides are transported in the form of electrons through the electron transport (respiratory) chain to molecular O2 to form H2O. The resulting free energy change is used to phosphorylate ADP to ATP. Enzymes of fatty acid oxidation, tricarboxylic acid cycle and respiration are located inside mitochondria. Energy status of cells can be described by the relative concentrations of adenine nucleotides (ATP, ADP and AMP) since the nucleotides act as allosteric modifiers of several key enzymes of energy metabolism. Energy is expended to synthesize and store fuel nutrients in utilizable forms (glycogen, triglycerides and proteins) and to maintain the storage forms in a dynamic steady state. The energy cost of such postprandial metabolic processes is defined as the "thermic" effect of food. Storage of dietary carbohydrates as adipose tissue triglycerides expends more energy than that of dietary fats. Overfeeding of certain individuals is known to burn more energy over and above that expected from the "thermic" effect and the process is referred to as "luxus consumption."(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Metabolismo Energético , Esforço Físico , Trifosfato de Adenosina/metabolismo , Células/metabolismo , Ciclo do Ácido Cítrico , Enzimas/metabolismo , Ácidos Graxos/metabolismo , Glicólise , Humanos , Mitocôndrias/metabolismo , Obesidade/metabolismo , Oxirredução , Fosforilação Oxidativa , Fosfocreatina/metabolismo
12.
J Clin Endocrinol Metab ; 56(4): 662-7, 1983 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6300159

RESUMO

We have studied the response of blood levels of progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, and cortisol to acute ACTH stimulation in children with isolated GH deficiency. Patients with isolated GH deficiency had generally higher levels of 11-deoxycortisol and lower levels of cortisol than controls both before and after ACTH stimulation. The steroid levels were almost completely restored to control levels after 3 months of treatment with GH. The pre-ACTH treatment levels of 11-deoxycortisol and cortisol were low in patients with both GH and ACTH deficiencies before and during GH therapy. Therefore, GH alone did not appear to have any effect on the hydroxylation of 11-deoxycortisol to cortisol. Before GH therapy, ACTH increased the concentrations of the two steroids. After GH therapy was started, the increase in 11-deoxycortisol was much smaller, but the increase in cortisol was much larger than before therapy. These results suggest a synergistic effect of GH on ACTH action on the biosynthesis of cortisol in the adrenals. Variations in the levels of 11-deoxycortisol and cortisol during hormonal manipulations lead to the identification of the mitochondrial hydroxylation of 11-deoxycortisol as one of the possible sites of action of GH.


Assuntos
17-Hidroxicorticosteroides/sangue , Cortodoxona/sangue , Hormônio do Crescimento/uso terapêutico , Hidrocortisona/sangue , Hipopituitarismo/tratamento farmacológico , Adolescente , Hormônio Adrenocorticotrópico/farmacologia , Criança , Pré-Escolar , Sinergismo Farmacológico , Feminino , Humanos , Hidroxiprogesteronas/sangue , Hipopituitarismo/sangue , Masculino , Progesterona/sangue
13.
Lipids ; 17(3): 129-35, 1982 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7087688

RESUMO

The effects of zinc deficiency and testosterone on fatty acid composition of plasma lipids and microsomes of liver, intestine and testes were studied. The activities of fatty acid desaturase (delta 6 and delta 5) in rat liver and testes were also measured. A significant decrease in the level of arachidonic acid was observed in plasma of normal rats fed the zinc-deficient diet. Castration significantly decreased arachidonic acid but increased 20:3 fatty acid, which is negligible in normal rats. Testosterone and zinc administration restored arachidonic acid to normal values. Zinc deficiency does not significantly change the fatty acid profile in liver, but castration decreased both arachidonic and 22:6 fatty acid. Intestinal mucosal microsomes showed that the predominant fatty acid in this tissue, palmitic acid, is independent of zinc status, whereas polyunsaturated fatty acids 18:2 and 20:4 were decreased by zinc-deficient diet or castration. Zinc deficiency sharply decreased 22:5 fatty acid and to some extent, other polyunsaturated fatty acids in testis microsomes. These changes in fatty acids are in agreement with increased delta 9 desaturation and decreased delta 5 desaturase activity. In testes, both delta 6 and delta 5 desaturase activities are decreased in zinc deficiency. It appears that zinc influences the conversion of linoleic to arachidonic acid, whereas testosterone influences delta 6 desaturase activity. The data suggest that zinc deficiency may be one of the important factors in the causation of polyunsaturated fatty acid deficiency, which, in turn, may induce serum hypertriglyceridemia.


Assuntos
Castração , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos/metabolismo , Zinco/deficiência , Animais , Ácidos Graxos/sangue , Mucosa Intestinal/metabolismo , Masculino , Microssomos/metabolismo , Microssomos Hepáticos/metabolismo , Ratos , Ratos Endogâmicos , Testículo/metabolismo , Testosterona/farmacologia
14.
Biochim Biophys Acta ; 678(2): 250-6, 1981 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-7317451

RESUMO

The effects of hypophysectomy and subsequent administration of growth hormone and/or L-thyroxine on thermotropic properties of State 3 respiration (ADP-induced), cholesterol, phospholipid and fatty acid composition of phospholipid fraction were examined in myocardial mitochondria of rats. Temperature-dependence of 1-anilino-8-naphthalene sulfonate fluorescence was determined in vesicles prepared from lipids of heart mitochondria. Transition temperature obtained from the Arrhenius plots of respiration occurred at 21 and 24 degrees C for heart mitochondria of normal and hypophysectomized rats, respectively. Most notably, after hypophysectomy the rate of respiration was lower below 24 degrees C, but was progressively higher above that temperature when compared to normal rats. The energy of activation was 148 and 36% larger below and above the transition temperature, respectively. Growth hormone restored almost completely the energy of activation and respiratory rates to normal levels. Administration of L-thyroxine, with or without growth hormone, did not significantly change the rate of respiration but decreased the transition temperature to 17.7-17.9 degrees C. Lipid and phospholipid content, as well as percent distribution of phospholipids and their fatty acid composition were not statistically different among the different groups of rats. Only cholesterol content was increased after hypophysectomy. Administration of growth hormone and thyroxine did not significantly change the total unsaturation index of fatty acids, but growth hormone increased the content of arachidonic acid (20 : 4) by 70% but decreased the docosahexaenoic acid (22 : 6) three times which may have a beneficial effect on mitochondrial membranes. These and other results suggest that hormones exert different effects on subcellular organelles in different tissues, like heart and liver.


Assuntos
Hormônio do Crescimento/farmacologia , Membranas Intracelulares/metabolismo , Lipídeos de Membrana/metabolismo , Mitocôndrias Cardíacas/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Tiroxina/farmacologia , Naftalenossulfonato de Anilina , Animais , Corantes Fluorescentes , Hipofisectomia , Membranas Intracelulares/efeitos dos fármacos , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Termodinâmica
15.
Am J Obstet Gynecol ; 141(7): 788-91, 1981 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-6172037

RESUMO

gamma-Glutamyl transpeptidase (GGTP) activity in normal amniotic fluids and corresponding maternal sera obtained at various gestational periods was measured. The ontogenic pattern of enzyme activity in amniotic fluid is very similar to alpha fetoprotein (AFP). However, the levels of these two proteins behaved differently in corresponding maternal sera. Also, in amniotic fluids obtained from pregnancies with neural tube defects (NTD), only AFP concentration was abnormally high whereas GGTP activity was normal.


Assuntos
Líquido Amniótico/enzimologia , Defeitos do Tubo Neural/enzimologia , alfa-Fetoproteínas/análise , gama-Glutamiltransferase/análise , Líquido Amniótico/análise , Feminino , Glutationa/análise , Humanos , Oxirredutases/análise , Gravidez
17.
Lipids ; 16(6): 454-60, 1981 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7266269

RESUMO

The effects of zinc deficiency and/or castration on the lipid composition of microsomal membranes of liver, small intestine and testes were studied in rats. The result showed that feeding a zinc-deficient diet to castrated rats decreased phospholipid content and consequently increased the cholesterol-to phospholipid ratio in liver microsomes. An increase in cholesterol-to phospholipid ration occurred also in small intestine and testes microsomes from rats fed the zinc-deficient diet. It is postulated, therefore, that zinc deficiency alters the lipid composition and fluidity of microsomal membranes. Zinc deficiency also affected tha activities of the enzymes involved in the formation of triglycerides and phospholipids. There was a large increase in total and specific activity of phosphatidate phosphatase and the changes in the total activity of choline phosphotransferase correlated well with the changes observed in serum or liver triglycerides and phospholipids. Stearoyl CoA desaturase, which is a control enzyme for hepatic lipogenesis, was also increased by more than 200% in zinc-deficient states, as was the diglyceride content of hepatic microsomes. These results indicate that the increased synthesis of triglycerides and phospholipids in zinc deficiency may be due to the increased availability of substrates as well as to increased activities of the enzymes involved in these processes.


Assuntos
Intestino Delgado/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Testículo/metabolismo , Zinco/deficiência , Animais , Castração , Colesterol/metabolismo , Membranas Intracelulares/metabolismo , Lipídeos/biossíntese , Fígado/enzimologia , Masculino , Microssomos/metabolismo , Microssomos Hepáticos/metabolismo , Fosfolipídeos/metabolismo , Ratos
19.
Am J Dis Child ; 135(4): 322-5, 1981 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7211791

RESUMO

Zinc levels were measured in hair and serum of boys with constitutional growth delay and familial short status and in several boys before and after oral administration of methyltestosterone. These results show the following: (1) zinc levels in boys beyond stage 3 of genital development are significantly higher than in stage 1 and 2; (2) there is a linear relationship between zinc levels and serum testosterone concentration (up to 250 ng/dL); and (3) methyltestosterone administration raised the zinc concentration in serum and hair, especially in boys with constitutional growth delay. Therefore, increased endogenous production or exogenous supply of testosterone are associated with increased zinc levels. We speculate that the relative testosterone deficiency and hypogonadotropism seen in constitutional growth delay may result in decreased zinc levels, which in turn could cause a further delay in the appearance of secondary sexual characteristics and greater growth retardation.


Assuntos
Transtornos do Crescimento/fisiopatologia , Testosterona/fisiologia , Zinco/fisiologia , Adolescente , Criança , Genitália Masculina/crescimento & desenvolvimento , Transtornos do Crescimento/tratamento farmacológico , Cabelo/análise , Humanos , Masculino , Metiltestosterona/uso terapêutico , Testosterona/sangue , Zinco/sangue
20.
Biochim Biophys Acta ; 657(1): 106-21, 1981 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-6260194

RESUMO

Thermotropic effects on the kinetics of glucose-6-phosphatase (D-glucose-6-phosphate phosphohydrolase, EC 3.1.3.9) activity of hepatic microsomes from normal and alloxan-diabetic rat liver were investigated by determining V, Km and Ki (substrate inhibition) values. Influence of deoxycholate (0.1%) and 1-anilino-8-naphthalene sulfonate (2.5 mM) on the kinetics was also evaluated. 1. Substrate inhibition occurred at 0.06 M for the enzyme from normal rats and at 0.0-0.025 M for the enzyme from diabetic rats. 2. The enzyme from diabetic rats showed a transition that extended between 22.7 and 27 degrees C in the Arrhenius plot (log V vs. T-1) instead of at 19.5 degrees C. 3. Deoxycholate increased the V value of both enzymes without affecting substrate inhibition at all the temperatures but did not completely abolish the transition in the Arrhenius plot of the enzyme from diabetic rats. 4. 1-Anilino-8-naphthalene sulfonate eliminated substrate inhibition and activated the enzyme of normal rats above 27.5 degrees C by increasing both V and Km values. Below this temperature, the enzyme showed biphasic or allosteric kinetics. At low substrate concentrations it was activated as both V and Km values were increased. The enzyme from diabetic rats, on the other hand, was activated at all the temperatures and exhibited linear kinetics. 5. Binding of 1-anilino-8-naphthalene sulfonate to the microsomal fraction increased with decreasing temperature as revealed by the increase of relative fluorescence. The microsomal fraction of diabetic rats showed a more anomalous fluorescence response between 13-18 degrees C. 6. Enthalpy changes for glucose 6-phosphate binding to the inhibition site were slightly larger than binding to the active site. Calculated entropies of activation for transition state complex of glucose-6-phosphatase reaction were fairly large and negative. The free energy of activation (28-30 kcal/mol) was independent of temperature and experimental conditions. 7. In the microsomal fraction (total as well as rough), phospholipid content and fatty acid unsaturation index of phospholipids were decreased after diabetes. The level of free cholesterol remained unchanged but the molar ratio of cholesterol to phospholipid increased. The different thermal response and 1-anilino-8-naphthalene sulfonate interaction to the enzyme from diabetic rat and liver could be ascribed to the altered lipid environment of the enzyme on the endoplasmic reticulum membrane.


Assuntos
Naftalenossulfonato de Anilina/farmacologia , Ácido Desoxicólico/fisiologia , Diabetes Mellitus Experimental/enzimologia , Glucose-6-Fosfatase/metabolismo , Microssomos Hepáticos/enzimologia , Temperatura , Animais , Ácidos Graxos/análise , Técnicas In Vitro , Cinética , Masculino , Fluidez de Membrana , Lipídeos de Membrana/análise , Ratos
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