scholarly journals Effects of glucagon and insulin on fatty acid synthesis and glycogen degradation in the perfused liver of normal and genetically obese (ob/ob) mice

1978 ◽  
Vol 174 (3) ◽  
pp. 761-768 ◽  
Author(s):  
G Y Ma ◽  
C D Gove ◽  
D A Hems
Keyword(s):  
Fatty Acid ◽  
Food Deprivation ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Biosynthesis ◽  
Glycogen Metabolism ◽  
Acid Synthesis ◽  
Significant Inhibition ◽  
Perfused Liver ◽  
Glucagon And Insulin ◽  
Glycogen Breakdown

1. Rapid effects of hormones on glycogen metabolism and fatty acid synthesis in the perfused liver of the mouse were studied. 2. In perfusions lasting 2h, of livers from normal mice, glucagon in successive doses, each producing concentrations of 10(-10) or 10(-9)M, inhibited fatty acid and cholesterol synthesis. In perfusions lasting 40–50 min, in which medium was not recycled, inhibition of fatty acid synthesis was only observed with glucagon at concentrations greater than 10(-9)M. This concentration was about two orders of magnitude higher than that required for the stimulation of glycogen breakdown. Glucagon did not inhibit the activity of acetyl-CoA carboxylase, assayed 10 or 20 min after addition of glucagon (10(-9) or 10(-10)M). It is proposed that the action of glucagon on hepatic fatty acid biosynthesis could be secondary in time to depletion of glycogen. Insulin prevented the effect of glucagon (10(-10)M) on glycogenolysis, but not that of vasopressin. 3. Livers of genetically obese (ob/ob) mice did not show significant inhibition of lipid biosynthesis in response to glucagon, although there was normal acceleration of glycogen breakdown. This resistance to glucagon action was not reversed by food deprivation. Livers of obese mice exhibited resistance to the counteraction by insulin of glucagon-stimulated glycogenolysis, which was reversible by partial food deprivation.

scholarly journals Resistance to hepatic action of vasopressin in genetically obese (ob/ob) mice

1976 ◽  
Vol 160 (1) ◽  
pp. 23-28 ◽  
Author(s):  
D A Hems ◽  
G Y Ma
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Inborn Error ◽  
Cholesterol Synthesis ◽  
Acid Synthesis ◽  
Hepatic Glycogen ◽  
Perfused Liver ◽  
Obese Mice ◽  
Hepatic Action ◽  
Glycogen Breakdown

1. Fatty acid synthesis, measured in the perfused liver of genetically obese (ob/ob) mice with 3H2O or [14C]actate, did not show the inhibition by [8-arginine]vasopressin (antidiuretic hormone) that is observed in livers from normal mice. 2. Hepatic glycogen breakdown in obese mice was stimuulated by vasopressin, but not as extensively as in lean mice. 3. If obese mice received a restricted amount of food, then fatty acid synthesis still did not respond to vasopressin, but glycogen breakdown was fully stimulated. 4. Cholesterol synthesis was not inhibited by vasopressin in livers from obese mice. 5. Vasopressin inhibited fatty acid synthesis in intact lean mice, but not in obese animals. 6. These results suggest that genetic obesity could be due to an inborn error within the mechanisms (other than adenylate cyclase) which mediate responses to extracellular effectors.

scholarly journals Fatty acid synthesis in the perfused liver of adrenalectomized rats

1976 ◽  
Vol 156 (3) ◽  
pp. 593-602 ◽  
Author(s):  
C J Kirk ◽  
T R Verrinder ◽  
D A Hems
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Direct Action ◽  
Acid Synthesis ◽  
Diabetic Rats ◽  
Perfused Liver ◽  
Control Sham ◽  
Adrenalectomized Rats

1. Fatty acid synthesis, measured in the perfused liver of fed adrenalectomized rats with 3H2O and 14C-labelled precursors, was less than in control sham-operated rats. 2. This defect was more extensive for synthesis of fatty acids incorporated into triacylglycerols than into phospholipids. 3. There was impairment in desaturation and export of newly synthesized fatty acid. 4. Fatty acid synthesis and desaturation were restored to normal rates 5h after treatment with cortisol in vivo. 5. Fatty acid synthesis was seasonally variable, being highest in the winter; the impairment after adrenalectomy was observed in all seasons. 6. In perfusions with oleate (0.7 mM), no further impairment in fatty acid synthesis was discerned in livers from adrenalectomized rats, in which the rate resembled that in control livers. 7. No defect in the incorporation of oleate into glycerides was discerned in livers from adrenalectomized rats. 8. Cortisol exerted no stimulatory effect on fatty acid synthesis when added to perfusion media. 9. The impairment in hepatic lipogenesis, demonstrable after adrenalectomy, shows that adrenal glucocorticoids promote hepatic capacity for fatty acid synthesis de novo, at least in intact non-diabetic rats. It is suggested that this effect is mediated by insulin, perhaps through direct action on the liver.

Mechanistic diversity and regulation of Type II fatty acid synthesis

2002 ◽  
Vol 30 (6) ◽  
pp. 1050-1055 ◽  
Author(s):  
H. Marrakchi ◽  
Y.-M. Zhang ◽  
C. O. Rock
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Unsaturated Fatty Acid ◽  
Fatty Acid Synthase ◽  
Fatty Acid Biosynthesis ◽  
Specific Interaction ◽  
Acid Synthesis ◽  
Protein Crystal ◽  
Type Ii ◽  
Acid Biosynthesis

Fatty acid biosynthesis is catalysed in most bacteria by a group of highly conserved proteins known as the Type II fatty acid synthase (FAS) system. The Type II system organization is distinct from its mammalian counterpart and offers several unique sites for selective inhibition by antibacterial agents. There has been remarkable progress in the understanding of the genetics, biochemistry and regulation of Type II FASs. One important advance is the discovery of the interaction between the fatty acid degradation regulator, FadR, and the fatty acid biosynthesis regulator, FabR, in the transcriptional control of unsaturated fatty acid synthesis in Escherichia coli. The availability of genomic sequences and high-resolution protein crystal structures has expanded our understanding of Type II FASs beyond the E. coli model system to a number of pathogens. The molecular diversity among the pathway enzymes is illustrated by the discovery of a new type of enoyl-reductase in Streptococcus pneumoniae [enoyl-acyl carrier protein (ACP) reductase II, FabK], the presence of two enoyl-reductases in Bacillus subtilis (enoyl-ACP reductases I and III, FabI and FabL), and the use of a new mechanism for unsaturated fatty acid formation in S. pneumoniae (trans-2-cis-3-enoyl-ACP isomerase, FabM). The solution structure of ACP from Mycobacterium tuberculosis revealed features common to all ACPs, but its extended C-terminal domain may reflect a specific interaction with very-long-chain intermediates.

scholarly journals A Type II Pathway for Fatty Acid Biosynthesis Presents Drug Targets in Plasmodium falciparum

2003 ◽  
Vol 47 (1) ◽  
pp. 297-301 ◽  
Author(s):  
Ross F. Waller ◽  
Stuart A. Ralph ◽  
Michael B. Reed ◽  
Vanessa Su ◽  
James D. Douglas ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Drug Targets ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Acid Synthesis ◽  
Type I ◽  
Type Ii ◽  
Parasite Survival ◽  
Fatty Acid Biosynthetic Pathway

ABSTRACT It has long been held that the malaria parasite, Plasmodium sp., is incapable of de novo fatty acid synthesis. This view has recently been overturned with the emergence of data for the presence of a fatty acid biosynthetic pathway in the relict plastid of P. falciparum (known as the apicoplast). This pathway represents the type II pathway common to plant chloroplasts and bacteria but distinct from the type I pathway of animals including humans. Specific inhibitors of the type II pathway, thiolactomycin and triclosan, have been reported to target this Plasmodium pathway. Here we report further inhibitors of the plastid-based pathway that inhibit Plasmodium parasites. These include several analogues of thiolactomycin, two with sixfold-greater efficacy than thiolactomycin. We also report that parasites respond very rapidly to such inhibitors and that the greatest sensitivity is seen in ring-stage parasites. This study substantiates the importance of fatty acid synthesis for blood-stage parasite survival and shows that this pathway provides scope for the development of novel antimalarial drugs.

scholarly journals Lipogenic enzymes in rat maternal adipose tissue in the perinatal period

1980 ◽  
Vol 186 (3) ◽  
pp. 937-944 ◽  
Author(s):  
P A Sinnett-Smith ◽  
R G Vernon ◽  
R J Mayer
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Pyruvate Dehydrogenase ◽  
Fatty Acid Biosynthesis ◽  
Specific Activity ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Acid Biosynthesis

1. The specific activities of fatty acid synthetase, acetyl-CoA carboxylase and pyruvate dehydrogenase were measured in rat adipose-tissue extracts in pregnancy and lactation. Fatty acid synthetase specific activity correlates very closely with the rate of fatty acid synthesis, the enzyme specific activity decreasing after mid-pregnancy in a manner very similar to the rate of fatty acid synthesis. Acetyl-CoA carboxylase specific activity also decreases dramatically after mid-pregnancy. Initial pyruvate dehydrogenase specific activity shows a decrease between 2 days pre partum and 2 days post partum, but total enzyme activity shows no significant change in the same period. 2. Immunotitrations of fatty acid synthetase and pyruvate dehydrogenase activities were carried out; the titrations showed that the change in the fatty acid synthetase activity is due to a change in the enzyme amount; the amount of pyruvate dyhydrogenase does not change. Therefore the decrease in fatty acid biosynthesis in subcutaneous and parametrial adipose tissue in late pregnancy and early lactation is associated with a decrease in the amount of at least one of the enzymes involved in fatty acid biosynthesis. The correlation of these events with known hormonal changes is discussed.

scholarly journals Role and Regulation of Fatty Acid Biosynthesis in the Response of Shewanella piezotolerans WP3 to Different Temperatures and Pressures

2009 ◽  
Vol 191 (8) ◽  
pp. 2574-2584 ◽  
Author(s):  
Feng Wang ◽  
Xiang Xiao ◽  
Hong-Yu Ou ◽  
Yingbao Gai ◽  
Fengping Wang
Keyword(s):  
Fatty Acids ◽  
High Pressure ◽  
Fatty Acid ◽  
Low Temperature ◽  
Gene Cluster ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Biosynthesis ◽  
Acid Synthesis ◽  
Different Temperatures ◽  
Branched Chain

ABSTRACT Members of the genus Shewanella inhabit various environments; they are capable of synthesizing various types of low-melting-point fatty acids, including monounsaturated fatty acids (MUFA) and branched-chain fatty acids (BCFA) with and without eicosapentanoic acid (EPA). The genes involved in fatty acid synthesis in 15 whole-genome-sequenced Shewanella strains were identified and compared. A typical type II fatty acid synthesis pathway in Shewanella was constructed. A complete EPA synthesis gene cluster was found in all of the Shewanella genomes, although only a few of them were found to produce EPA. The roles and regulation of fatty acids synthesis in Shewanella were further elucidated in the Shewanella piezotolerans WP3 response to different temperatures and pressures. The EPA and BCFA contents of WP3 significantly increased when it was grown at low temperature and/or under high pressure. EPA, but not MUFA, was determined to be crucial for its growth at low temperature and high pressure. A gene cluster for a branched-chain amino acid ABC transporter (LIV-I) was found to be upregulated at low temperature. Combined approaches, including mutagenesis and an isotopic-tracer method, revealed that the LIV-I transporter played an important role in the regulation of BCFA synthesis in WP3. The LIV-I transporter was identified only in the cold-adapted Shewanella species and was assumed to supply an important strategy for Shewanella cold adaptation. This is the first time the molecular mechanism of BCFA regulation in bacteria has been elucidated.

scholarly journals Only One of the Five Ralstonia solanacearum Long-Chain 3-Ketoacyl-Acyl Carrier Protein Synthase Homologues Functions in Fatty Acid Synthesis

2011 ◽  
Vol 78 (5) ◽  
pp. 1563-1573 ◽  
Author(s):  
Juanli Cheng ◽  
Jincheng Ma ◽  
Jinshui Lin ◽  
Zhen-Chuan Fan ◽  
John E. Cronan ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Ralstonia Solanacearum ◽  
Fatty Acid Biosynthesis ◽  
Acyl Carrier Protein ◽  
Acid Synthesis ◽  
Carrier Protein ◽  
Phytopathogenic Bacterium ◽  
Content Type ◽  
Long Chain

ABSTRACTRalstonia solanacearum, a major phytopathogenic bacterium, causes a bacterial wilt disease in diverse plants. Although fatty acid analyses of total membranes ofR. solanacearumshowed that they contain primarily palmitic (C16:0), palmitoleic (C16:1) andcis-vaccenic (C18:1) acids, little is known regardingR. solanacearumfatty acid synthesis. TheR. solanacearumGMI1000 genome is unusual in that it contains four genes (fabF1,fabF2,fabF3, andfabF4) annotated as encoding 3-ketoacyl-acyl carrier protein synthase II homologues and one gene (fabB) annotated as encoding 3-ketoacyl-acyl carrier protein synthase I. We have analyzed this puzzling apparent redundancy and found that only one of these genes,fabF1, encoded a long-chain 3-ketoacyl-acyl carrier protein synthase, whereas the other homologues did not play roles inR. solanacearumfatty acid synthesis. Mutant strains lackingfabF1are nonviable, and thus, FabF1 is essential forR. solanacearumfatty acid biosynthesis. Moreover,R. solanacearumFabF1 has the activities of both 3-ketoacyl-acyl carrier protein synthase II and 3-ketoacyl-acyl carrier protein synthase I.

scholarly journals Fatty acid biosynthesis in rabbit mammary gland during pregnancy and early lactation

1972 ◽  
Vol 128 (5) ◽  
pp. 1303-1309 ◽  
Author(s):  
Christopher R. Strong ◽  
Raymond Dils
Keyword(s):  
Fatty Acids ◽  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Biosynthesis ◽  
Acid Synthesis ◽  
Decanoic Acid ◽  
Early Lactation ◽  
Wet Weight ◽  
Rabbit Milk

The pattern of fatty acids synthesized by mammary-gland explants from rabbits during pregnancy and early lactation has been studied. From day 12 to day 18 of pregnancy, long-chain (C14:0–C18:1) fatty acids were the major products. From day 18 to day 21 of pregnancy there was an increase of up to 12-fold in the rate of fatty acid synthesis per unit wet weight of tissue that was almost exclusively caused by the synthesis of octanoic fatty acid and decanoic fatty acid, which are characteristic of rabbit milk. These medium-chain fatty acids were mainly incorporated into triglycerides. From day 22 to day 27 of pregnancy there was little change in the rate of fatty acid synthesis and the proportions of fatty acids synthesized were essentially the same as those synthesized by the lactating gland, i.e. 80–90% octanoic acid plus decanoic acid. About 2–4 days before parturition a second lipogenic stimulus occurred, although the pattern of fatty acids synthesized did not change.

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