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PubMed1981

Effect of cimetidine on deoxyribonucleic acid biosynthesis in gastrointestinal mucosa of rats.

Using oxyntic and duodenal rat tissues, we investigated the effects of cimetidine, an antisecretagogue and a H2-receptor antagonist, on deoxyribonucleic acid (DNA) biosynthesis, determined according to the 3H-thymidine incorporation into DNA fraction. Serum gastrin concentration and DNA biosynthesis in the tissues increased significantly in the fed rats, and administration of cimetidine significantly increased both serum gastrin concentration and the DNA biosynthesis in the oxyntic tissues. There was a significant correlation between the oxyntic DNA biosynthesis and the serum gastrin concentration. Cimetidine in concentrations of 0.01 to 1.0 mM, added to the incubation mixture, had no stimulatory effect on the DNA biosynthesis in the oxyntic tissues. These results support the hypothesis that DNA biosynthesis in oxyntic mucosa of rats may be regulated by the circulating gastrin.

Animals↗
PubMed2003

Apolipoprotein C-III isofocusing in the diagnosis of genetic defects in O-glycan biosynthesis.

BACKGROUND: Defects in the biosynthesis of N-glycans may be found by isoelectric focusing (IEF) of plasma transferrin. No test is available to demonstrate O-glycan biosynthesis defects. METHODS: We used isoforms of apolipoprotein C-III (apoC-III) as a marker for the biosynthesis of core 1 mucin type O-glycans. Plasma samples from patients with primary defects and secondary alterations in N-glycan biosynthesis were studied by apoC-III isofocusing. RESULTS: Age-related reference values for apoC-III were determined. Plasma samples from patients with the primary congenital disorders of glycosylation (CDG) types Ia-Ic, Ie, If, IIa, and IId all showed a normal apoC-III isofocusing profile. Plasma from two patients with CDG type IIx were tested: one showed a normal apoC-III distribution, whereas the other showed a hypoglycosylation profile. In plasma from patients with hemolytic uremic syndrome (HUS), a hypoglycosylation profile was obtained. CONCLUSIONS: IEF of apoC-III is a rapid and simple technique that may be used as a screening assay for abnormalities in core 1 mucin type O-glycans. Evidence that a patient in this study has a primary genetic defect affecting both N- and O-glycosylation provides the first example of an inborn error of metabolism affecting the biosynthesis of core 1 mucin type O-glycans. Our data narrow the options for the position of the primary defect in this patient down to a step in the biosynthesis, activation, or transfer of galactose or N-acetylneuraminic acid to both N- and O-glycans. Circulating neuraminidase excreted by Streptococcus pneumoniae caused the high percentage of asialo apoC-III in two HUS patients.

Adolescent↗
PubMed2006

Transferrin and apolipoprotein C-III isofocusing are complementary in the diagnosis of N- and O-glycan biosynthesis defects.

BACKGROUND: Apolipoprotein C-III (apoC-III) isoelectric focusing (IEF) can be used to detect abnormalities in the biosynthesis of core 1 mucin-type O-glycans. METHODS: We studied plasma samples from 55 patients with various primary defects in N- and/or O-glycosylation, 21 patients with secondary N-glycosylation defects, and 6 patients with possible glycosylation abnormalities. Furthermore, we analyzed 500 plasma samples that were sent to our laboratory for selective screening for inborn errors of metabolism. RESULTS: Plasma samples from patients with congenital disorders of glycosylation (CDG) types -IIe and -IIf showed a hypoglycosylated apoC-III isoform profile, as did plasma samples from 75% of the patients with an unspecified CDG type II. Hyposialylated O-glycan profiles were also seen in plasma from 2 patients with hemolytic-uremic syndrome. In the 500 plasma samples from the selective screening, 3 patients were identified with a possible isolated defect in the biosynthesis of core 1 mucin-type O-glycans. CONCLUSIONS: To our knowledge this is the first study in which use of a plasma marker protein has identified patients in whom only O-glycan biosynthesis might be affected. The primary defect(s) remain as yet unknown. Plasma apoC-III IEF is complementary to transferrin isofocusing. In conjunction both tests identify biosynthesis defects in N-glycan and mucin-type core 1 O-glycan biosynthesis. The apoC-III IEF assay is likely to help metabolic laboratories to identify and unravel further subtypes of inborn errors of glycan biosynthesis.

Adolescent↗
PubMed1998

PACAP activates calcium influx-dependent and -independent pathways to couple met-enkephalin secretion and biosynthesis in chromaffin cells.

Pituitary adenylate cyclase activating polypeptide-27 (PACAP-27) caused a dose-dependent increase in met-enkephalin secretion and increased production of met-enkephalin peptide and proenkephalin A (PEnk) mRNA in bovine chromaffin cells, at concentrations as low as 300 pM. PACAP-38 was less potent than PACAP-27, but had similar effects. Vasoactive intestinal polypeptide (VIP) (1-100 nM) was without appreciable effect on either enkephalin secretion or biosynthesis, implicating PACAP type I receptors in PACAP-stimulated enkephalin secretion and synthesis. PACAP type I receptors can activate adenylate cyclase and stimulate phospholipase C through heterotrimeric G protein interactions, leading to increased intracellular cyclic AMP (cAMP), inositol triphosphate (IP3)-mediated calcium mobilization, and calcium- and diacylglycerol (DAG)-mediated protein kinase C (PKC) activation. Enkephalin secretion evoked by 10-100 nM PACAP-27 was not inhibited by 1 microM (-)-202-791, an L-type specific dihydropyridine calcium channel blocker, but was inhibited 65-80% by the arylalkylamine calcium channel blocker D600. Forty mM potassium-evoked secretion was inhibited > 90% by both D600 and (-)-202-791, 25 microM forskolin-induced secretion was blocked < 50% by D600 and was unaffected by (-)-202-791, and 100 nM phorbol myristate acetate (PMA)-induced secretion was unaffected by either D600 or (-)-202-791. Enkephalin biosynthesis was increased by 10 nM PACAP-27, as measured by increased met-enkephalin pentapeptide content and PEnk A mRNA levels. PACAP-, forskolin-, and PMA-stimulated enkephalin synthesis were not blocked by D600 or (-)-202-791. Elevated potassium-induced enkephalin biosynthesis upregulation was completely blocked by either D600 or (-)-202-791 at the same concentrations. PACAP acting through type I PACAP receptors couples calcium influx-dependent enkephalin secretion and calcium influx-independent enkephalin biosynthesis in chromaffin cells. Restriction of the effects of enhanced calcium influx to stimulation of secretion, but not of biosynthesis, is unique to PACAP. By contrast, potassium-induced enkephalin biosynthesis upregulation is completely calcium influx dependent, specifically via calcium influx through L-type calcium channels. We propose that subpopulations of voltage-dependent calcium channels are differentially linked to intracellular signal transduction pathways that control neuropeptide gene expression and secretion in chromaffin cells.

Adrenal Glands↗
PubMed1975

[The relations between lactation and cyclic-AMP -- The influences of adenyl cyclase activity on casein biosynthesis ability in the organ culture of the mouse mammary gland (author's transl)].

The relationships between hormonal action and cyclic AMP as the second messenger of hormones have recently been discussed on many hormones. Lactation is influenced by various hormone, especially, insulin, prolactin, and hydrocortisone. Whether adenyl cyclase activity in the mammary gland of mouse epithelial cells has parallel relations with casein biosynthesis ability or not was examined using the mammary gland organ culture method. Female, mid-pregnant (11-14 days), mice of DDY strain were used. Organ culture was done by the Chen's floating lens' paper method, using the hormone-added MEM media and non-added ones. Casein biosynthesis ability was measured by observing 32P incorporation into the casein molecules. Adenyl cyclase activity was estimated by the amount of 14-C-cyclic AMP produced out of adenine-8-14C by the Kuo and Krishna's method. Radio isotope compounds were pulsed for 4 hours in the medium. The experiments revealed that the added hormones had a remarkable effect on caein biosynthesis ability, but none on adenyl cyclase activity. No parallel fluctuation was observed between adenyl cyclase activity and casein biosynthesis ability, that is, the change of adenyl cyclase activity was found to have nothing to do with casein biosynthesis ability. Consequently, the cyclic AMP addition to the media showed no effect on casein biosynthesis ability.

Adenylyl Cyclases↗
PubMed2003

Enediyne natural products: biosynthesis and prospect towards engineering novel antitumor agents.

This review gives a brief account on the current status of enediyne biosynthesis and the prospective of applying combinatorial biosynthesis methods to the enediyne system for novel analog production. Methods for cloning enediyne biosynthetic gene clusters are first reviewed. A unified paradigm for enediyne biosynthesis, characterized with (a) the enediyne PKS, (b) the enediyne PKS accessory enzymes, and (c) tailoring enzymes, is then presented. Strategies and tools for novel enediyne analog production by combinatorial biosynthesis are finally discussed. The results set the stage to decipher the molecular mechanism for enediyne biosynthesis and lay the foundation to engineer novel enediynes by combinatorial biosynthesis for future endeavors.

Antineoplastic Agents↗
PubMed2003

Insulin does not mediate glucose stimulation of proinsulin biosynthesis.

It has recently been suggested that insulin augments its own production by a physiologically important feed-forward autocrine loop. We studied the kinetics of glucose-regulated proinsulin gene expression and proinsulin biosynthesis in normal rat islets with emphasis on the potential role of insulin as a mediator of the glucose effect. There was a time-dependent increase in steady-state proinsulin mRNA in islets cultured at 16.7 mmol/l compared with 3.3 mmol/l glucose; no early (1-3 h) increase in proinsulin gene expression was observed. In contrast, there was a threefold increase in proinsulin biosynthesis within 1 h of glucose stimulation that was not affected by inhibition of glucose-stimulated proinsulin gene transcription with actinomycin D. In addition, inhibition of glucose-stimulated insulin secretion with diazoxide had no effect on glucose-stimulated proinsulin mRNA or biosynthesis. Furthermore, addition of different concentrations of insulin to islets cultured in low glucose failed to affect proinsulin biosynthesis. Taken together, our data suggest that the early glucose-dependent increase in proinsulin biosynthesis is mainly regulated at the translational level, rather than by changes in proinsulin gene expression. Moreover, we could not demonstrate any effect of insulin on islet proinsulin mRNA level or rate of proinsulin biosynthesis. Thus, if insulin has any effect on the proinsulin biosynthetic apparatus, it is a minor one. We conclude that the secreted insulin is not an important mediator of insulin production in response to glucose.

Animals↗
PubMedDate not supplied

Evidence that the effect of soya bean phosphatidylinositol-cholesterol-cyclosporin liposomes on the biosynthesis of acidic phospholipids in isolated subcellular membranes from rat liver and heart is attributable to the soya bean phosphatidylinositol-cholesterol liposomes.

This study examined the effect of adding soya bean phosphatidylinositol-cholesterol (2:1 molar ratio) liposomes and soya bean phosphatidylinositol-cholesterol (2:1 molar ratio)-cyclosporin liposomes on the biosynthesis of [3H]polyglycerophosphatides (phosphatidylglycerolphosphate, phosphatidyl-glycerol and cardiolipin) and [3H]phosphatidylinositol in mitochondria and microsomes, respectively, isolated from rat liver and heart. The results obtained with liposomes, and liposomes containing cyclosporin, established that cyclosporin did not participate in the metabolism of acidic phospholipids. In rat liver and heart mitochondria the amount of biosynthesized [3H]polyglycerophosphatides fell to one-third and a half respectively in comparison with the amounts found when liposomes were not added. The composition of [3H]polyglycerophosphatides in both mitochondria showed an increased accumulation of [3H]phosphatidylglycerolphosphate with a concomitant decrease of about 30 per cent in [3H]phosphatidylglycerol. The biosynthesis of [3H]phosphatidylinositol in both rat liver and rat heart microsomes fell to one-third of that found in the absence of liposomes. Under similar conditions the biosynthesis of [3H]cardiolipin decreased by 50 per cent in both mitochondria. The incubation of the same liposomes and liposomes containing cyclosporin with isolated rat liver mitochondria and microsomes released about 5-7 per cent of the linoleic acid. When a corresponding amount of linoleic acid was added to the incubation mixture, the biosynthesis of [3H]polyglycerophosphatides in rat liver did not change significantly, whereas in rat heart mitochondria this biosynthesis decreased by about 33 per cent. Under these conditions, the accumulation of [3H]phosphatidylglycerolphosphate and the decrease of [3H]phosphatidylglycerol was established. The biosynthesis of [3H]phosphatidylinositol in the presence of linoleic acid in rat liver and rat heart microsomes was significantly reduced. Under similar conditions the addition of stearic acid did not significantly affect the level or composition of biosynthesized [3H]polyglycerophosphatides or biosynthesized [3H]phosphatidylinositol.

Animals↗
PubMed2000

Inborn errors of cholesterol biosynthesis.

Disorders of cholesterol biosynthesis have recently emerged as important errors of metabolism that collectively have taught us many new genetic and biochemical lessons. Whereas most metabolic diseases are characterized by exclusively or largely postnatal biochemical toxicities or deficiencies, disorders of cholesterol biosynthesis are notable for their severe effects on prenatal development. The remarkable embryonic consequences of abnormal cholesterol biosynthesis are exemplified by Smith-Lemli-Opitz syndrome (SLOS), a well-known multiple congenital anomaly syndrome only recently discovered to be caused by a deficiency in the last step in cholesterol biosynthesis. Equally surprising has been the discovery that primary defects of cholesterol biosynthesis cause several different forms of congenital skeletal dysplasia, most notably X-linked dominant chondrodysplasia punctata, or Conradi-Hünermann syndrome. Yet another sterol disorder, desmosterolosis, caused by defective activity of desmosterol reductase, combines a severe osteosclerotic skeletal dysplasia with multiple embryonic malformations similar to those of SLOS. The discovery of the biochemical basis of these diverse genetic disorders has provided not only accurate biochemical methods for their diagnosis and prenatal diagnosis, but also new insights into the biochemistry of vertebrate embryonic development. Among the lessons we have learned from the study of inborn errors of cholesterol biosynthesis, one of the most important is that the abnormal cholesterol metabolism of SLOS impairs the function of "Sonic hedgehog" and other related embryonic "signaling proteins" that help determine the vertebrate body plan during the earliest weeks of embryonic development. Most significant clinically has been the realization that many of the postnatal clinical problems of patients with SLOS are direct consequences of the inability to synthesize the large amounts of cholesterol needed for growth and for the synthesis of compounds derived from cholesterol, such as steroid hormones. In addition to the important finding that supplementary cholesterol eliminates or ameliorates many of the feeding and growth problems of SLOS, the discovery that the autistic behaviors of children with SLOS can be reduced or even eliminated by treatment with supplementary dietary cholesterol has been one of the most startling. Moreover, clinical and basic research on prenatal cholesterol nutrition in SLOS and various animal model systems has delineated a previously unrecognized system for the delivery of low-density lipoprotein cholesterol from the mother to the developing embryo. The many discoveries engendered by these experiments of nature argue that there are heretofore unrecognized beneficial effects of cholesterol, especially in children, and that we should consider very carefully possible adverse effects that the popular war against cholesterol may have on the prenatal and postnatal development of children.

Autistic Disorder↗
PubMed1975

[Effect of vitamin B6 group on cholesterol and fatty acid biosynthesis (author's transl)].

The effect of vitamin B6 groups, pyridoxine, pyridoxamine, pyridoxal (pyridoxal phosphate and pyridoxal phosphate Ca) on hepatic cholesterol and fatty acid biosynthesis in mice were studied. 1. Acetate-14C incorporation rate into cholesterol and fatty acid in pyridoxal phosphate supplement in vitro increased remarkably, relative to pyridoxine or pyridoxamine. 2. When daily subcutaneous injection of pyridoxal phosphate or pyridoxal phosphate Ca were given to normal mice, pyridoxal phosphate produced the decrease of liver cholesterol biosynthesis and cholesterol levell and the increase of fatty acid biosynthesis and fatty acid level, while pyridoxal phosphate Ca did not produce any significant changes, relative to the normal groups. 3. The dietary cholesterol supplement given pyridoxine fed mice did not produce any changes in liver cholesterol and fatty acid synthesis, and liver cholesterol level, while the increase of liver fatty acid and blood cholesterol biosynthesis were seen. Pyridoxal phosphate Ca plus cholesterol feeding did not produce any changes in liver cholesterol and fatty acid biosynthesis, and liver fatty acid levels and blood cholesterol biosynthesis, while the increase of liver cholesterol leve was seen, relative to the cholesterol fed group.

Animals↗
PubMed1991

[The effect of steroid sex hormones on the biosynthesis of alpha 2-macroglobulin and pregnancy-associated alpha 2-glycoprotein in cultures of peripheral blood mononuclear cells].

The peripheral blood mononuclears are capable of intense biosynthesis of alpha 2-macroglobulin and of weak biosynthesis of pregnancy-associated alpha 2-glycoprotein. Sex hormones of men and non-pregnant women exert no influence on the protein biosynthesis. During pregnancy alpha 2-macroglobulin biosynthesis is shortly activated, although it does not depend on the influence of sex hormones. All the steroid sex hormones provide a short-term biosynthesis of this protein during the II trimester of pregnancy, while testosteron inhibits it during the III trimester. Possible mechanisms of control of biosynthesis of these proteins are discussed.

Cells, Cultured↗
PubMed1990

Effect of a novel anti-inflammatory drug, 2-(10, 11-dihydro-10-oxo-dibenzo[b,f]-thiepin-2-yl)propionic acid (CN-100), on the proteoglycan biosynthesis in articular chondrocytes and prostaglandin E2 production in synovial fibroblasts.

The effect of a novel nonsteroidal anti-inflammatory drug, 2-(10,11-dihydro-10-oxo-dibenzo[b,f]thiepin-2-yl)propionic acid (CN-100), on the biosynthesis of proteoglycans in chondrocytes of rat femoral head articular cartilage was studied. Sodium salicylate and hydrocortisone inhibited significantly the biosynthesis proteoglycans, but CN-100 did not affect the biosynthesis of glycosaminoglycan chains nor their sulfation. The effect of CN-100 on the interleukin 1-induced biosynthesis of prostaglandin E2 (PGE2) and tissue collagenase in rabbit and human rheumatoid synovial fibroblasts was also examined. CN-100 did not inhibited directly the collagenase production, but significantly prevent the biosynthesis of PGE2 known as an inflammatory mediator. The 50% inhibitory concentration (IC50) of CN-100 on PGE2 of rabbit and human fibroblasts were 3.8 x 10(-9) M and 2.4 x 10(-8) M, respectively; an inhibitory effect of CN-100 was equivalent to that of a control drug, hydrocortisone (2.0 x 10(-9) M and 1.7 x 10(-8) M, respectively). These results indicate that CN-100 is a potent anti-inflammatory drug without affecting the proteoglycan biosynthesis.

Animals↗
PubMed1989

BioSYNTHESIS: bridging the information gap.

BioSYNTHESIS is a prototype intelligent retrieval system under development as part of the IAIMS project at Georgetown University. The aim is to create an integrated system that can retrieve information located on disparate computer systems. The project work has been divided in two phases: BioSYNTHESIS I, development of a single menu to access various databases which reside on different computers; and BioSYNTHESIS II, development of a search component that facilitates complex searching for the user. BioSYNTHESIS II will accept a user's query and conduct a search for appropriate information in the IAIMS databases at Georgetown. For information not available at Georgetown, such as full text, it will access selected remote systems and translate the search query as appropriate for the target system. The search through various computer systems and different databases with unique storage and retrieval structures will be transparent to the user. BioSYNTHESIS I is complete and available to users. The design work for BioSYNTHESIS II is under development and will continue as a multiyear technical research effort of the proposed Georgetown IAIMS implementation project.

Computer Communication Networks↗
PubMed1988

Profiles of prostaglandin biosynthesis in normal lung and tumor tissue from lung cancer patients.

prostaglandin (PG) biosynthetic profiles from endogenous arachidonic acid were determined by capillary gas chromatography-mass spectrometry in matched fresh normal lung (NL) and lung cancer (LC) tissue fragments obtained from 42 individual LC patients at the time of diagnostic thoracotomy. The histological diagnoses represented were squamous cell carcinoma (N = 20), adenocarcinoma (N = 7), small cell carcinoma (N = 4), mixed cell carcinoma (N = 2), bronchioloalveolar cell carcinoma (N = 2), large cell undifferentiated carcinoma (N = 3), bronchial carcinoid (N = 1), and metastatic tumors (N = 3). When PG biosynthesis was determined in NL tissue separately, low mean levels of PGE2 and PGF2 alpha (less than 2 pmol/mg protein/15 min), intermediate levels of PGD2 and 6-keto-PGF1 alpha (6KPGF1 alpha) (2-7 pmol/mg protein/15 min), and high levels of thromboxane B2 (TXB2) (greater than 7 pmol/mg protein/15 min) were observed. There was no particular correlation with cigarette smoking history and PG biosynthesis in NL. When PG production in LC tissue was evaluated separately, high levels of PGE2, PGF2 alpha, and 6KPGF1 alpha as well as TXB2 and low levels of PGD2 were noted. In addition, LC tissue from cigarette smokers demonstrated elevated levels of PGE2, 6KPGF1 alpha, and TXB2 when compared to current nonsmokers with LC (P less than 0.05 in all instances). Simultaneous comparison of PG production in matched LC and NL tissue from individual patients indicated increased biosynthesis of PGE2 and PGF2 alpha and low levels of PGD2 in LC compared to NL tissue (P less than 0.05 in all instances; paired, two-tailed, Student's t test). Individual comparison of PG biosynthesis according to LC histological cell type revealed that PGE2 and PGF2 alpha were consistently elevated in all four common primary LC histological cell types, the only exception being large cell undifferentiated carcinoma. Interestingly, this latter LC histological cell type presented a unique profile with lower levels of PGE2 and PGD2 in LC than in NL tissue (P less than 0.05 in both instances). In addition, the biosynthesis of all 5 PGs studied was consistently higher in primary than metastatic adenocarcinomas of the lung (P less than 0.05 in all instances). No differences were observed in NL and LC tissue for the major LC histological cell types when PGD2, TXB2, or 6KPGF1 alpha biosyntheses were compared. These findings indicate that the profiles of PG biosynthesis in LC and NL tissue from individual patients may differ substantially. These differences may reflect, in part, contributions to the PG biosynthetic profile unique to malignant cells.

Arachidonic Acid↗
PubMed1988

Plasmalogen biosynthesis in peroxisomal disorders: fatty alcohol versus alkylglycerol precursors.

In recent years a growing number of inherited diseases have been recognized to originate from an impairment in one or more peroxisomal functions. Since it is well established that the first two steps in the biosynthesis of plasmalogens proceed in peroxisomes, we studied the biosynthesis of plasmalogens in cultured skin fibroblasts from patients with different peroxisomal and related disorders. When de novo plasmalogen biosynthesis was studied by growing the cells in the presence of [14C]hexadecanol, impaired plasmalogen biosynthesis was found in rhizomelic chondrodysplasia punctata, cerebrohepatorenal (Zellweger) syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease. In all these cases, alkyl-acyl phospholipids, the precursors of plasmalogens, did not accumulate and 1-O-[9,10-3H2]octadecylglycerol was converted into plasmalogens with equal efficiency as in controls. This indicated that impaired de novo plasmalogen biosynthesis as measured by [14C]hexadecanol incorporation was due to a deficient formation of the glycero-ether bond. Using this procedure, normal de novo plasmalogen biosynthesis was found in X-linked adrenoleukodystrophy, adrenomyeloneuropathy, X-linked chondrodysplasia punctata, adult Refsum disease, as well as in heterozygotes for Zellweger syndrome and infantile Refsum disease. The data have indicated that the average extent of the deficiency in glycero-ether bond formation is different in Zellweger syndrome, chondrodysplasia punctata, neonatal adrenoleukodystrophy, and infantile Refsum disease.

Cells, Cultured↗
PubMed1981

[Activities of 3-hydroxy-3-methylglutaryl-CoA reductase and acetyl-CoA carboxylase and rate of biosynthesis of mevalonic acid, squalene, sterols and fatty acids from [1-14C]acetyl-CoA and [2-14C]malonyl-CoA in rat liver: changes induced by daily rhythm].

The activity of 3-hydrosy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and the rate of mevalonic acid (MVA) synthesis from [I-14C]acetyl-CoA and [2-14C]malonyl-CoA in the soluble (X140000 g) and microsomal fractions of rat liver and in a reconstituted system containing the soluble and microsomal fractions were studied. The changes in the activity of HMG-CoA reductase and the rate of MVA biosynthesis in the fractions at different times of the day were analyzed. The daily rhythms of the rate of acetyl-CoA and malonyl-CoA incorporation into squalene, sterols and fatty acids in the postmitochondrial fraction and the daily changes in the acetyl-CoA carboxylase activity of the soluble fraction of rat liver were compared. The incorporation of labelled acetyl-CoA and malonyl-CoA into MVA showed that the latter can be synthesized from these two substrates both in the soluble and microsomal fractions. Malonyl-CoA is a preferable substrate for MVA synthesis in the soluble fraction. MVA synthesis from acetyl-CoA proceeds fastr in the intact and solubilized microsomes than in the soluble fraction. The activity of HMG-CoA reductase was found in the soluble and microsomal fractions in practically equal amounts. The enzyme activity was increased in the microsomal fraction after its solubilization. The rate of MVA biosynthesis from acetyl-CoA and the activity of HMG-CoA reductase in the soluble fraction are practically unaffected by day-to-night changes. The activity of HMG-CoA reductase and MVA biosynthesis from acetyl-CoA in the intact and solubilized microsomal fractions reached their maximal values in the middle of the dark period. The rate of MVA biosynthesis from malonyl-CoA was decreased in the middle of the dark period in all fractions studied and reached its maximum in the middle of the light period. The daily rhythms of the acetyl-CoA carboxylase activity in the soluble fraction and the rate of MVA biosynthesis from malonyl-CoA in all fractions show a coincidence. a comparison of incorporation by the postmitochondrial fractions of acetyl-CoA and malonyl-CoA into the total non-saponified lipid fraction and its components, e. g. squalene, lanosterol and cholesterol, as well as into sterols precipitated by digitonin, showed that malonyl-CoA incorporation into the total non-saponified lipid fraction was more intensive than that of acetyl-CoA. However, acetyl-CoA was far more efficiently incorporated into sterols precipitated by digitonin or isolated by TLC than malonyl-CoA. The rate of acetyl-CoA incorporation into the total non-saponified lipid fraction and into squalene, lanosterol and cholesterol was maximal in the middle of the dark period and minimal in the middle of the light period. On the contrary, the rate of malonyl-CoA incorporation into these products was minimal in the middle of the dark period and maximal in the middle of the light period. The rate of fatty acid biosynthesis from acetyl-CoA was increased in the middle of the light and dark periods...

Acetyl Coenzyme A↗
PubMed1980

Studies on inhibition of nucleic acid biosynthesis by isoniazid and its possible prevention.

Effect of isoniazid on nucleic acid biosynthesis was studied in Swiss mice. It was observed that i.p. injection of isoniazid stimulated activities of nuclease. Isoniazid also inhibits RNA biosynthesis in lung and liver tissue of 3-weeks old mice but has no inhibitory effect on the same in 6 weeks old mice. It inhibits DNA biosynthesis in lung tissue of 3- and 6-week old mice. With the decrease in nucleic acid biosynthesis and increased activities of nucleases the nucleotide pool is increased. I.p. injection of ammonium chloride produces inhibition of nucleic acid biosynthesis to a similar extent. Administration of amino acids L-arginine or L-Na-glutamate or of vitamins pyridoxine or folic acid along with isoniazid prevents the inhibitory effect of isoniazid on nucleic acid biosynthesis.

Animals↗
PubMedDate not supplied

[Extracellular protease biosynthesis in Aspergillus candidus in the absence of carbon or sulfur sources].

The absence of carbon, nitrogen and sulfur sources in the medium was shown to be a prerequisite for the production of exocellular proteases by Aspergillus candidus. The biosynthesis of proteases stops as soon as a limiting substrate is added to the medium. The rate of protease biosynthesis noticeably decreases if proline, alanine, glycine, valine, phenylalanine, serine, threonine, aspartic and glutamic acids are added, particularly during the first hours of incubation. Cysteine increases the delay in the onset of protease biosynthesis. Tryptophan, leucine, asparagine and glutamine considerable decrease the rate of exoprotease biosynthesis throughout the experiment. Arginine, histidine, lysine, ornithine and methionine added to the medium without a carbon source almost entirely inhibit the biosynthesis of exoproteases. A sulfur-deficient fungal mycelium synthesizes exoproteases at a high rate in the medium without a sulfur source whereas sulfate, methionine and cysteine suppress the process. Protein, being the only source of carbon, nitrogen or sulfur in the medium, abruptly decreases the rate of exoprotease biosynthesis.

Amino Acids↗