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R A Coleman

Publications and source records attributed to R A Coleman.

At least 91 records · Page 5Linked to original sources
PubMed1994

Galactose consumption, metabolism, and follicle-stimulating hormone concentrations in women of late reproductive age.

OBJECTIVE: To test the hypothesis that high galactose consumption and low activity of galactose-1-phosphate uridyl transferase (transferase) is associated with early ovarian senescence among nongalactosemic women. DESIGN: Cross-sectional study. Data collection consisted of a self-administered questionnaire with sections on diet (food frequency data to measure galactose consumption), reproductive, and medical histories. One blood sample was collected to measure FSH and transferase activity; FSH was used as a measure of ovarian senescence. Among women who were having menstrual periods at least every 8 weeks, the blood sample was drawn in the early follicular phase (days 2 to 4) of a menstrual cycle. PARTICIPANTS: Two hundred ninety-five women volunteers ages 38 to 49 years who had not had a hysterectomy or oophorectomy were recruited through posters and advertisements. MAIN OUTCOME MEASURE: Serum FSH concentrations. RESULTS: Controlling for age, smoking, and body mass, transferase activity and FSH were unrelated. However, FSH levels were 29% higher (95% confidence intervals, 9% to 52%) among women who reported consuming > or = 6 g galactose/d. CONCLUSION: These data do not support the hypothesis that low transferase activity represents a genetic predisposition for early ovarian senescence, as measured by FSH levels in women ages 38 to 49 years. However, the hypothesized positive association between galactose consumption and FSH was supported.

Adult↗
PubMed1994

Characterization of dilator prostanoid receptors in the fetal rabbit ductus arteriosus.

The purpose of this study was to determine which receptors mediate the dilator effects of prostaglandins (PGs) on the ductus arteriosus of the fetal rabbit. Isolated rings of the vessel from fetal New Zealand White rabbits were precontracted with indomethacin (1 microM) and potassium (25 mM) in 100 to 110 mmHg oxygen, and the dilator effects of a range of synthetic prostanoids were quantified by cumulative relaxant concentration-effect curves. The potencies of agonists were quantified with reference to PGE2 by the equieffective molar ratio (EMR): EC50 test agonist/EC50 PGE2. The effects on these responses of available antagonists were also studied. None of a range of synthetic prostanoids with selective agonism of EP1, EP2 or EP3 receptors was as potent as PGE2. The rank order of potency was as follows: PGE2 (EC50 = 0.36 nM [95% confidence intervals [CI] = 0.32-0.41, n = 44], EMR = unity) >> misoprostol (EMR 145, 95% CI 73-217) > [1R-[1 alpha (Z),2 beta (R*),3 alpha]]-4-(benzoyl-amino)phenyl 7-[3 hydroxy-2(2-hydroxy-3-phenoxypropoxy)-5- oxocyclopentyl]-4-heptenoate, single enantiomer (GR 63799K) (EMR 685, 95% CI 427-944) >> ((+/-)-trans-2-[4[(1-hydroxphenyl) phenyl]-5-oxocylopentaneheptanoic acid (AH13205) (EMR > 100,000) > or = sulprostone (EMR > 10,000) > or = 0. The EP1 antagonists, 6-isopropoxy-9-oxoxanthine-2-carboxylic acid (AH6809) (10 microM) and 8-clorodi-benz[b,f][1,4]oxazepine-10 (11H)-carboxylic acid, 2-acetylhydrazide (SC19220) (30 microM), had no significant effect on the sensitivity of the ductus to PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Increased hepatic monoacylglycerol acyltransferase activity in streptozotocin-induced diabetes: characterization and comparison with activities from adult and neonatal rat liver.

Hepatic monoacylglycerol acyltransferase (EC 2.3.1.22) (MGAT) is a developmentally-expressed activity associated with physiological periods characterized by high rates of lipolysis and dependence on fatty acids for energy production. During these periods, MGAT may help to retain essential fatty acids selectively. In streptozotocin-diabetes, mean MGAT-specific activity increased 11.8-fold. We characterized microsomal MGAT activity from diabetic and control adult rats, and compared these adult activities with the high neonatal activity. Compared with the activity in neonatal liver, adult MGAT activity was more thermolabile, had a markedly different pH profile, and responded differently to incubation with bovine serum albumin, phospholipids, and MnCl2. Adult diabetic MGAT activity was also stimulated 2-fold by albumin and was markedly thermolabile, but was not inhibited by phospholipid. Diabetic MGAT activity had some properties that combined characteristics observed in adult and neonatal microsomes: a pH dependence that was optimal at pH 7.0 but that plateaued between pH 7.0 and 9.5, and neither stimulation nor inhibition after incubation with MnCl2. Diabetic MGAT acylated monoalkylglycerols more readily than did either the neonatal or the adult MGAT activities. The enhanced expression of hepatic MGAT activity in diabetes is consistent with its postulated role in retaining essential fatty acids during lipolysis.

Acyltransferases↗
PubMed1993

Characterization of choline metabolism and secretion by human placental trophoblasts in culture.

Choline is an essential nutrient for fetal development and may be utilized to form phospholipids such as phosphatidylcholine and sphingomyelin; to synthesize the neurotransmitter, acetylcholine; and to donate methyl groups after being oxidized to betaine. Since the majority of choline required for fetal growth must be transported by the placenta from the maternal circulation, we examined the ability of isolated human trophoblasts to metabolize choline and to release choline and its metabolites into culture medium. Cytotrophoblasts were isolated from normal, full-term human placentas and incubated with [14C]choline for 3 h; the cells were washed to remove extracellular radiolabel, and the changes in intracellular and medium choline pools were followed for an additional 24 h. During the incubation, choline rapidly reached steady state intracellularly and label was incorporated into betaine, phosphocholine, cytidylyldiphosphocholine, phosphatidylcholine, glycerophosphocholine, lysophosphatidylcholine, and sphingomyelin. All labeled choline metabolites in cells, except glycerophosphocholine, decreased at 6 and 27 h of incubation (3 and 24 h, respectively, after labeled choline was removed), and labeled metabolites appeared in media. By 24 h after labeled choline was removed, the major labeled metabolites in the media were choline (82%), betaine (11%), and glycerophosphocholine (5%). Small amounts of phosphatidylcholine (1%), and lysophosphatidylcholine (1%) were found. Acetylcholine was a very minor choline metabolite in these cells. When placental cells were incubated for 66 h after isolation, they formed syncytiotrophoblasts, which incorporated labeled choline into metabolites in a similar pattern to cytotrophoblasts. These data indicate that isolated trophoblast cells can metabolize choline to form all of its major metabolites and that several metabolites are released to the medium in significant amounts. Thus, our data suggest that the major metabolite supplied to the fetus may be choline, but that betaine and glycerophosphocholine may also be vehicles for transfer of choline equivalents from mother to fetus.

Betaine↗
PubMed1993

Solubilization and partial purification of neonatally expressed rat hepatic microsomal monoacylglycerol acyltransferase.

Rat hepatic microsomal monoacylglycerol acyltransferase (MGAT) is a developmentally expressed enzyme that catalyzes the formation of sn-1,2-diacylglycerol from sn-2-monoacylglycerol and fatty acyl-CoA. Treatment of suckling rat liver microsomes with various detergents showed that 0.3% Triton X-100, a nonionic detergent, solubilized a maximum amount of both protein (66%) and MGAT activity (56%). After solubilization with Triton X-100, MGAT was then purified 205-fold by sequential chromatography on QAE-Sephadex, CM-Sepharose (Fast Flow), and hydroxylapatite. Addition of phospholipids to the reaction mixture stimulated the purified enzyme activity more than 1.8-fold. sn-1,2-DiC18: 1-glycerol activated purified MGAT activity. Purified MGAT activity was specific for sn-2-monoacylglycerol; the activity with rac-1-monoC18:1-glycerol and rac-1- and sn-2-monoC18:1-glycerol ethers was less than 4% of the activity with sn-2-monoC18:1-glycerol. The purified MGAT had an isoelectric point of 9.7. The apparent Km and Vmax values of the purified enzyme for sn-2-monoC18:1-glycerol were 21 microM and 1036 nmol/min/mg, respectively. The apparent Km value for palmitoyl-CoA was 6.5 microM. Purified MGAT activity acylated sn-2-monoC18:2-glycerol and sn-2-monoC18:3-glycerol in preference to sn-2-monoC18:1-glycerol, consistent with a role for the monoacylglycerol pathway in retaining essential fatty acids.

Acyltransferases↗
PubMed1993

Hepatic monoacylglycerol acyltransferase activity in HA1 and HA7 hepatoma/hepatocyte hybrid cells: regulation by insulin and dexamethasone and by cell density.

Hepatic monoacylglycerol acyltransferase (MGAT) (EC 2.3.1.22) is a developmentally-expressed enzyme that catalyzes the stereospecific synthesis of sn-1,2-diacylglycerol from sn-2-monoacylglycerol and long-chain fatty acyl-CoA. In order to study the regulation of MGAT, we developed a rapid assay that can be performed directly on permeabilized HA rat hepatocyte/hepatoma hybrid cells, a line that expresses levels of hepatic MGAT activity and a lipogenic program characteristic of fetal hepatocytes. In permeabilized HA cells, MGAT activity was proportional to the time of incubation and was highly dependent on added sn-2-monoacylglycerol and palmitoyl-CoA. The apparent Km values were 16.6 and 12.7 microM for palmitoyl-CoA and 2-monooleoylglycerol, respectively. Activity was low with the 1(3)- and sn-2-ether analogs of monooleoylglycerol, supporting the conclusion that the cells express the hepatic isoenzyme of MGAT. MGAT activity increased directly with cell density and was unrelated to the number of days in culture. Long-term incubation (2-4 days) of HA cells with various hormones (including triiodothyronine, human placental lactogen, epidermal growth factor, glucagon and growth hormone) showed that only a combination of dexamethasome and insulin resulted in significantly decreased MGAT activity. None of these hormones affected MGAT activity in short-term (0.5-4 h) incubations. These studies suggest that the developmental decline in rat hepatic MGAT activity may be regulated by glucocorticoids and insulin, hormones that increase during and after the second postnatal week.

Acyltransferases↗
PubMed1993

Seasonal changes in critical enzymes of lipogenesis and triacylglycerol synthesis in the marmot (Marmota flaviventris).

Fatty acid metabolism and triacylglycerol synthesis are critical processes for the survival of hibernating mammals that undergo a prolonged fasting period. Fatty acid synthase, fatty-acid-CoA ligase, diacylglycerol acyltransferase, and monoacylglycerol acyltransferase activities were measured in liver and in white and brown adipose tissue, in order to determine whether enzymes of lipogenesis and triacylglycerol synthesis vary seasonally during hibernation in the yellow-bellied marmot (Marmota flaviventris). Compared with mid-winter hibernation, fatty acid synthase activity was higher in all three tissues during early spring when marmots emerged from hibernation and in mid-summer when they were feeding, consistent with the synthesis of fatty acids from the carbohydrate-rich summer diet. Fatty-acid-CoA ligase and diacylglycerol acyltransferase activities were highest in summer in white adipose tissue when triacylglycerol synthesis would be expected to be high; diacylglycerol acyltransferase activity was also high in brown adipose tissue during spring and summer. In liver, however, diacylglycerol acyltransferase specific activity was highest during hibernation, suggesting that triacylglycerol synthesis may be prominent in liver in winter. Monoacylglycerol acyltransferase activity, which may aid in the retention of essential fatty-acids, was 80-fold higher in liver than in white or brown adipose tissue, but did not vary seasonally. Its dependence on palmitoyl-CoA suggests that a divalent cation might play a role in enzyme activation. The high hepatic diacylglycerol acyltransferase activity during hibernation suggests that the metabolism of very low density lipoprotein may be important in the movement of adipose fatty acids to brown adipose tissue and muscle during the rewarming that occurs periodically during hibernation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyltransferases↗
PubMed1993

Type I glycogen storage disease: nine years of management with cornstarch.

Long-term effects of cornstarch (CS) therapy on biochemical values and physical growth in children with type I glycogen storage disease (GSD I) were compared to those of children receiving continuous nocturnal nasogastric glucose feedings (CNG). Only patients who had received more than 5 years of dietary therapy (either CS or CNG) were evaluated. Six patients (five female, age 13.5 years +/- 1.3, range 11.7-16.5 years) received CS (1.75-2.5 g/kg, four times daily) and seven patients (five female, age 9.6 +/- 2.5 years, range 7.3-14.8 years) received CNG. Blood glucose, lactate, cholesterol and triglyceride levels were not significantly different between the two methods of treatment. All patients maintained linear growth rates normal for their age. The standard deviation score of height after 6.7 +/- 1.6 years (range 5-9 years) of CS treatment was -1.29 +/- 0.59 and after 8.8 +/- 2.4 years (range 7-14 years) of CNG was -1.24 +/- 0.63. These values did not differ significantly from each other or from the target height, an estimate of genetic potential for height as determined from parental heights. With the exceptions of diarrhea, increased flatulence and excess weight gain, there were no adverse effects of CS after 9 years of treatment. Our data suggests that cornstarch is a simple, effective and safe therapy for GSD I.

Adolescent↗
PubMed1993

The pharmacology of salmeterol.

Salmeterol was developed to provide prolonged bronchodilatation to control nocturnal symptoms and improve maintenance therapy in asthmatic patients. Salmeterol is > 10,000 times more lipophilic than salbutamol and has greater affinity for the beta 2-adrenoceptor. Membrane binding is non-competitive and dissociation is slow so that its effects last for many hours. Despite this, salmeterol does not accumulate in tissues. Its mechanism of action can be explained by binding to a specific exo-site domain of the beta 2-receptor protein to produce continuous stimulation of the active site of the receptor, which gives salmeterol a profile of pharmacological activity unlike that of other beta 2-agonists. Due to its potent and prolonged activation of beta 2-adrenoceptors in airway smooth muscle cells, endothelial cells, mast cells and epithelial cells, salmeterol induces prolonged bronchodilatation, reduced vascular permeability, inhibition of inflammatory mediators, stimulation of ciliary function and modulation of ion and water transport across the bronchial mucosa.

Adrenergic beta-Agonists↗
PubMed1993

Investigations into factors determining the duration of action of the beta 2-adrenoceptor agonist, salmeterol.

1. This study has explored the mechanism underlying the long duration of action of the beta 2-adrenoceptor agonist, salmeterol. 2. Salmeterol, salbutamol and isoprenaline caused a concentration-related inhibition of electrically-induced contractile responses of the guinea-pig superfused trachea preparation. The effects of both isoprenaline and salbutamol were rapid in onset and rapidly reversed upon removal of the agonist. In contrast, the effects of salmeterol were slower in onset and could not be reversed by superfusion of the tissue with agonist-free Krebs solution even for periods of up to 10 h. 3. The effects of salmeterol were, however, readily reversed by a number of beta-adrenoceptor blocking drugs, as was the effect of a continuous infusion of isoprenaline. Upon removal of the antagonist, however, the effects of salmeterol and of the isoprenaline infusion were reasserted at a rate which was inversely related to the lipophilicity of a beta-adrenoceptor blocking drugs. 4. Salmeterol inhibited the binding of [125I]-(-)-iodopindolol (100 pM) to rat lung membranes (pIC50 7.1), with isoprenaline (pIC50 6.2) and salbutamol (pIC50 5.1) having lower potencies. The inhibition of binding by salmeterol was apparently non-competitive, whereas that produced by salbutamol and isoprenaline was competitive in nature. 5. Isoprenaline and salbutamol rapidly dissociated from their binding sites, whereas in marked contrast, the binding of salmeterol showed no dissociation for periods of up to 1 h. 6. These data are consistent with the mechanism in which salmeterol binds adjacent to the active site of the beta 2-adrenoceptor, such that the drug cannot be washed out of the tissue, yet can interact with and activate the receptor. This latter property is susceptible to antagonism by beta-adrenoceptor blocking drugs but is reassured when the antagonists are removed.

Adrenergic beta-Agonists↗
PubMed1993

Effects of beta-adrenoceptor agonists in human bronchial smooth muscle.

1. We have investigated the potency and duration of action of isoprenaline and a range of beta-adrenoceptor agonists as relaxants of inherent tone in human superfused, isolated bronchial smooth muscle, a tissue reported to contain a homogeneous population of beta 2-adrenoceptors. 2. All of the beta-adrenoceptor agonists caused concentration-related inhibition of inherent tone, with isoprenaline having an EC50 of 27 nM. The rank order of agonist potency was: formoterol > or = -salmeterol > or = clenbuterol > fenoterol = isoprenaline > terbutaline > or = salbutamol > quinprenaline. 3. Relaxant responses to salmeterol were fully reversed by the selective beta 2-adrenoceptor blocking drug, ICI 118551, demonstrating the involvement of beta 2-adrenoceptors. 4. Rt50, i.e. the time taken for 50% recovery from the effects of an EC50 concentration of agonist, differed considerably between the different beta 2-adrenoceptor agonists. Most agonists were short-acting, having Rt50 values less than 13 min. Quinprenaline was of moderate duration, with an Rt50 value of > or = 20 min. In contrast, salmeterol was extremely long-acting, with no sign of recovery within 4 h. 5. Estimates of relative potency and duration of action were similar to those previously determined for these agonists in the guinea-pig isolated trachea. These results suggest, therefore, that guinea-pig trachea is a suitable alternative to human bronchus for the evaluation of the actions of beta-adrenoceptor agonists on airways smooth muscle.

Adrenergic beta-Agonists↗
PubMed1993

The action of Hoe 140 on the bradykinin-induced splenic pressor reflex of the anaesthetized cat.

1. Intrasplenic injection of bradykinin (BK) induced a dose-dependent pressor response in the anaesthetized cat, with an ED50 of 0.98 +/- 0.43 nmol. In contrast, intrasplenic administration of desArg9bradykinin (desArg9BK) was without significant effect at doses of up to 200 nmol. 2. Intravenously administered BK induced a dose-dependent depressor response in the anaesthetized cat, with an ED50 of 0.86 +/- 0.09 nmol kg-1. desArg9BK was again without significant effect in this system at doses of up to 200 nmol kg-1. 3. Both the pressor and depressor responses to BK were antagonized to a similar degree in a dose-dependent manner by Hoe 140 (10 and 100 nmol kg-1, i.v.). 4. At these doses, Hoe 140 appears to be a specific BK antagonist as it was ineffective against pressor responses to intrasplenic injection of capsaicin (5 nmol), while blocking those to an approximately equieffective dose of BK (1 nmol) in a dose-dependent fashion. 5. Both the pressor response to intrasplenic BK and the depressor response to intravenous BK in the anaesthetized cat appear to be mediated by B2-receptors. This model may be useful in the quantitative determination of the antinociceptive potency of BK antagonists.

Animals↗
PubMed1993

Lincosamide antibiotics stimulate dissociation of peptidyl-tRNA from ribosomes.

At nonpermissive temperatures the peptidyl-tRNA hydrolase of pth(Ts) bacterial mutants is inactivated, and cells accumulate peptidyl-tRNA and die. Doses of erythromycin, lincomycin, or clindamycin that inhibited the growth of antibiotic-hypersensitive DB-11 pth+ cells accelerated the killing of DB-11 pth(Ts) cells at nonpermissive temperatures. Erythromycin and lincomycin also stimulated the accumulation of peptidyl-tRNA. Lincomycin and clindamycin stimulated peptidyl-tRNA dissociation from ribosomes.

Anti-Bacterial Agents↗
PubMed1993

Selective retention of essential fatty acids: the role of hepatic monoacylglycerol acyltransferase.

In the suckling rat, chick embryo, and hibernating marmot, fatty acids provide the major source of energy, and despite the high rate of hepatic beta-oxidation, these animals selectively retain long-chain polyunsaturated derivatives of C18:2n-6 and C18:3n-3. To determine whether the hepatic microsomal activity monoacylglycerol acyltransferase (MGAT) (EC 2.3.1.22) could provide a mechanism to selectively acylate monoacylglycerols that contain essential fatty acids, we tested the ability of MGAT activity from each of the three species to acylate sn-2-monoC18:1-, sn-2-monoC18:2-, sn-2-monoC18:3-, and sn-2-monoC20:4-glycerols. Hepatic MGAT activity acylated sn-2-monoC18:3-glycerol and sn-2-monoC18:2-glycerol in preference to sn-2-monoC18:1-glycerol in each of the three different lipolytic animals. MGAT's acyl group specificity could not be explained by invoking differences in membrane fluidity because the apparent affinity for sn-2-monoC20:4-glycerol was not increased. Further, sn-2-monoC18:3-glycerol remained a preferred substrate under assay conditions when both the C18:3 and C18:1 species were present in equal amounts. As would be predicted in the presence of high activity of a selective MGAT, the hepatic glycerolipids from neonatal rats showed increases in dienoic, trienoic, and C22:6 fatty acids and relative decreases in monoenoic, saturated, and C20:4 fatty acids. We hypothesize that, during lipolysis, the reacylation of sn-2-monoacylglycerols by MGAT may provide a mechanism by which essential fatty acids are retained within specific tissues.

Acylation↗
PubMed1992

Diacylglycerol metabolism in neonatal rat liver: characterization of cytosolic diacylglycerol lipase activity and its activation by monoalkylglycerols.

Diacylglycerol lipase (glycerol ester hydrolase, EC 3.1.1.3) activities were investigated in subcellular fractions from neonatal and adult rat liver in order to determine whether one or more different lipases might provide the substrate for the developmentally expressed, activity monoacylglycerol acyltransferase. The assay for diacylglycerol lipase examined the hydrolysis of sn-1-stearoyl,2- [14C]oleoylglycerol to labeled monoacylglycerol and fatty acid. Highest specific activities were found in lysosomes (pH 4.8) and cytosol and microsomes (pH 8). The specific activity from plasma membrane from adult liver was 5.8-fold higher than the corresponding activity in the neonate. In other fractions, however, no developmental differences were observed in activity or distribution. In both lysosomes and cytosol, 75 to 90% of the labeled product was monoacylglycerol, suggesting that these fractions contained relatively little monoacylglycerol lipase activity. In contrast, 80% of the labeled product from microsomes was fatty acid, suggesting the presence of monoacylglycerol lipase in this fraction. Analysis of the reaction products strongly suggested that the lysosomal and cytosolic diacylglycerol lipase activities hydrolyzed the acyl-group at the sn-1 position. The effects of serum and NaCl on diacylglycerol lipase from each of the subcellular fractions differed from those effects routinely observed on lipoprotein lipase and hepatic lipase, suggesting that the hepatic diacylglycerol lipase activities were not second functions of these triacylglycerol lipases. Cytosolic diacylglycerol lipase activity from neonatal liver and adult liver was characterized. The apparent Km for 1-stearoyl,2-oleoylglycerol was 115 microM. There was no preference for a diacylglycerol with arachidonate in the sn-2 position. Bovine serum albumin stimulated the activity, whereas dithiothreitol, N-ethylmaleimide, and ATP inhibited the activity. Both sn-1(3)- and 2-monooleylglycerol ethers stimulated cytosolic diacylglycerol lipase activity 2-3-fold. The corresponding amide analogs stimulated 28 to 85%, monooleoylglycerol itself had little effect, and 1-alkyl- or 1-acyl-lysophosphatidylcholine inhibited the activity. These data provide the first characterization of hepatic subcellular lipase activities from neonatal and adult rat liver and suggest that independent diacylglycerol and monoacylglycerol lipase activities are present in microsomal membranes and that the microsomal and cytosolic diacylglycerol lipase activities may describe an ambipathic enzyme. The data also suggest possible cellular regulation by monoalkylglycerols.

Aging↗
PubMed1992

Glycogen storage disease type III (glycogen debranching enzyme deficiency): correlation of biochemical defects with myopathy and cardiomyopathy.

OBJECTIVE: To determine whether a specific subtype of glycogen storage disease type III is associated with myopathy and cardiomyopathy. DESIGN: Case series. SETTING: Three referral medical centers. PATIENTS: All patients with glycogen storage disease type III who were followed in 1990 and for whom both immunoblot analysis and clinical data were available. MAIN OUTCOME MEASURES: Evaluation for myopathy and cardiomyopathy included determinations of serum creatine kinase activity; muscle strength testing; ischemic exercise testing; nerve conduction studies; and electromyographic, electrocardiographic, and echocardiographic studies. RESULTS: Three patients with deficient debranching enzyme activity and deficient immunoreactive material in liver but normal debranching enzyme activity in muscle (glycogen storage disease IIIb) had no clinical evidence of myopathy or cardiomyopathy. Serum creatine kinase activity, muscle strength, ischemic exercise testing, electrocardiograms, and echocardiograms were normal in these patients. These studies and electromyograms were abnormal in seven patients with total debranching enzyme deficiency and an absence of immunoreactive material in both liver and muscle (glycogen storage disease IIIa) and in three patients who had debranching enzyme transferase deficiency but normal glucosidase activity in both liver and muscle (glycogen storage disease IIId). All 10 of these patients had progressive myopathy, and 6 had progressive cardiomyopathy. CONCLUSION: Clinical features of glycogen storage disease type III correlate with the particular biochemical defect seen with the disorder. Assessments of debranching enzyme or debranching enzyme transferase activity in muscle can be used to predict whether patients with glycogen storage disease type III will develop myopathy and cardiomyopathy.

Adolescent↗
PubMed1992

2-Bromopalmitoyl-CoA and 2-bromopalmitate: promiscuous inhibitors of membrane-bound enzymes.

2-Bromopalmitate and 2-bromopalmitoyl-CoA have been shown to inhibit a variety of enzymes and proteins associated with lipid metabolism. We found that both of the brominated compounds were non-competitive inhibitors of two microsomal activities of triacylglycerol biosynthesis, the mono- and diacylglycerol acyltransferases. With both compounds, the calculated Ki values were lower than the Km value for the palmitoyl-CoA substrate. In addition to inhibiting two other lipid synthetic activities, fatty acid CoA ligase and glycerol-3-P acyltransferase, 2-bromopalmitate and 2-bromopalmitoyl-CoA also inhibited two microsomal enzyme activities that are not related to lipid metabolism, NADPH cytochrome-c reductase and glucose-6-phosphatase. Inhibition of the three acyltransferases and fatty acid CoA ligase could be overcome by the addition of phospholipid vesicles, and 2-bromo[14C]palmitate readily labeled a large number of membrane-bound proteins as well as cytosolic proteins that had been solubilized in SDS. Thus, it appears likely that the inhibitory properties of the brominated compounds strongly depend on the effective concentration of the inhibitor within membranes rather than on any specific affinity for an acyl-chain binding region of the enzyme.

Acyltransferases↗