Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.79 (hormone-sensitive lipase)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hormone-sensitive lipase, a key enzyme in fatty acid mobilization, overall energy homeostasis, and possibly steroidogenesis, is acutely controlled through reversible phosphorylation by catecholamines and insulin. The 757-amino acid sequence predicted from a cloned rat adipocyte complementary DNA showed no homology with any other known lipase or protein. The activity-controlling phosphorylation site was localized to Ser563 in a markedly hydrophilic domain, and a lipid-binding consensus site was tentatively identified. One or several messenger RNA species (3.3, 3.5, or 3.9 kilobases) were expressed in adipose and steroidogenic tissues and heart and skeletal muscle. The human hormone-sensitive lipase gene mapped to chromosome 19 cent-q13.3.
 ...
PMID:Hormone-sensitive lipase: sequence, expression, and chromosomal localization to 19 cent-q13.3. 342 Apr 5

Progressive weight loss and anorexia are frequent phenomena in cancer patients. Although cachexia is an expected occurrence in the terminal stages of nearly all malignancies, it may be a presenting sign when the tumor burden is quite small. Lipid depletion occurs out of proportion to the protein loss and accounts for most of the weight loss in cancer. Lipids, more specifically fatty acids, are the major source of fuel in mammals and may also be used in the synthesis of new cell products. Lipolysis and lipogenesis are under the influence of several important enzymes and peptide hormones that may be modulated by a variety of exogenous factors. There is evidence that cancer patients have lost the normal homeostatic responses to decreased energy intake or starvation that allow a decrease in oxygen consumption and protein sparing. An increase in Cori cycle activity or futile recycling of metabolic products occurs with a net energy expenditure rather than energy production. Clinical studies have shown that the body lipid depletion accompanying tumor progression is not solely secondary to decreased food intake and may be reproduced by the transplantation of certain noninvasive tumors to normal hosts. Elevated basal lipolysis has occasionally been seen early in tumor growth. Such findings suggest the presence of a tumor-associated factor responsible for this increase in lipid mobilization. Some of the potential mechanisms for the altered lipid metabolism seen in cancer have been discussed. Metabolic substrates may be remodeled and directed away from fuel-efficient into energy-requiring pathways. An increased energy expenditure may occur as a result of the energy costs of tumor synthesis, an uncoupling of oxidative phosphorylation, or energy-requiring futile cycling. An overall depletion of lipid may be the final outcome of the inhibition of lipid deposition. TNF/cachectin has recently been found to suppress the activity and synthesis of several key lipogenic enzymes, including lipoprotein lipase. Abnormalities in insulin secretion or sensitivity may be involved in the decrease of fat storage in malignancy. Insulin also exerts a significant antilipolytic effect by its antagonism of hormone-sensitive lipase. Mediators of lipolysis and abnormal lipid metabolism may occur in a number of clinical conditions and include ectopic hormone production, growth factors, and tumor-associated lipolytic factors (lipid mobilizing factor, toxohormone).
 ...
PMID:Fat metabolism and cancer. 353 75

A polyclonal rabbit antibody was used to detect hormone-sensitive lipase in rat organs other than white adipose tissue. Inhibition of tissue diacylglycerol lipase activity by the anti-hormone-sensitive lipase, and by NaF, Hg2+ and diisopropyl fluorophosphate, known inhibitors of the hormone-sensitive lipase, demonstrated its presence in the adrenals, ovaries, testes, heart and skeletal muscle, but not in the liver and kidneys. After enrichment by immunoprecipitation an immunoreactive protein, corresponding to the adipose tissue hormone-sensitive lipase 84 kDa subunit, and some additional, higher Mrapp proteins, were detected by Western blotting in the same tissues. The adipose tissue contained greater than 80% of the total hormone-sensitive lipase, with 5-10- and 50-100-fold lower specific activity in the steroid-producing and the muscle tissues, respectively.
 ...
PMID:Immunological evidence for the presence of hormone-sensitive lipase in rat tissues other than adipose tissue. 367 97

Experiments were conducted to examine the effects of dietary saturated fatty acids on the intracellular free fatty acid concentration and composition and on the kinetic parameters of hormone-sensitive lipase of rat adipocytes. Animals were fed for 4 wk 14% coconut oil, beef fat or safflower oil and 2% corn oil in a purified diet. Adipocytes of animals fed the coconut oil diet contained higher basal level of intracellular free fatty acids than those of animals fed other beef fat or safflower oil diets. Norepinephrine (10(-5) M) stimulated the basal intracellular free fatty acid concentration by 2.3-3.4-fold in adipocytes from animals fed saturated fatty acids, compared with 6.4-fold in those of animals fed the safflower oil diet. The concentrations of intracellular free fatty acids in adipocytes of experimental animals after stimulation with 10(-5) M norepinephrine, however, were not significantly different. The intracellular free fatty acid pool of adipocytes of animals fed the saturated fatty acids had more palmitic acid and less linoleic acid than those of safflower oil-fed animals. The results indicate that type of dietary fat had no effect on kinetic properties of hormone-sensitive lipase.
 ...
PMID:Effect of dietary saturated fatty acids on intracellular free fatty acids and kinetic properties of hormone-sensitive lipase of rat adipocytes. 372 4

Biological activities of estrogen molecules are altered by fluorination of ring A, and the resulting impairment to form catechols. 2-fluoroestradiol (2-F-E2) has been found to be devoid of carcinogenic action despite its high estrogenic potency; its metabolic effects are so far unknown. This study was designed to investigate the effects of 2-F-E2 on lipid metabolism, as compared to those of estradiol-17 beta(E2). Ovariectomized rats received E2 or 2-F-E2 by s.c. injection at a dose of 60 micrograms for three consecutive days. Parameters measured were weights of parametrial fat depots, fat cell volumes, levels of triacylglycerol and acylcholesterol in plasma, and enzymatic responses to the estrogens in isolated parametrial fat cells as evaluated in terms of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities. 2-F-E2 and E2 were found to produce comparable decreases in fat depots, cell volumes and plasma levels of acylcholesterol whereas plasma triacylglycerol was unchanged. Both estrogens decreased LPL, and increased HSL activities to the same extent. Thus, 2-F-E and E2 exhibited comparable effects on lipid metabolism. These effects appeared to depend mainly on the estrogenic potency of these molecules, and to be distinct from their carcinogenic action. Despite its high estrogenic potency, 2-F-E2 was found to be slightly less estrogenic than E2.
 ...
PMID:Effects of 2-fluoroestradiol on lipid metabolism in the ovariectomized rat. 377 28

Temperature-induced phase separation in Triton X-114 (Bordier, C. (1981) J. Biol. Chem. 256, 1604-1607) and charge-shift electrophoresis (Helenius, A., and Simons, K. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 529-532) were used to examine the amphiphilic character of hormone-sensitive lipase, purified from rat adipose tissue. In contrast to ATP-citrate lyase, a reference hydrophilic protein, the lipase was shown to partition predominantly (approximately 80%) into the detergent-rich phase upon phase separation in Triton X-114. Furthermore, its electrophoretic mobility was markedly shifted anodally and cathodally upon charge-shift electrophoresis in the presence of sodium taurodeoxycholate and cetyltrimethylammonium bromide, respectively. The results demonstrate that hormone-sensitive lipase possesses detergent-binding hydrophobic domain(s) and exhibits the same amphiphilicity as typical intrinsic membrane proteins.
 ...
PMID:Demonstration of the amphiphilic character of hormone-sensitive lipase by temperature-induced phase separation in Triton X-114 and charge-shift electrophoresis. 378 81

We have developed an improved method for purification of hormone-sensitive lipase from adipose tissue. The method employs two preparative high-performance ion-exchange chromatography steps on Mono Q and Mono S after detergent solubilization and partial fractionation of the enzyme by gradient sievorptive chromatography on QAE-Sephadex. About 0.2 mg of greater than 70% pure enzyme is prepared at 10% yield within 6-7 days from adipose tissue of 500 rats. This protocol is a major improvement over the previously established procedure in terms of accessibility, rapidity, enzyme purity, and yield.
 ...
PMID:Purification of hormone-sensitive lipase by high-performance ion exchange chromatography. 381 80

The newly described immunoglobulin G-binding streptococcal surface protein, protein G, was used to prepare and characterize rabbit antibodies. The antibodies were directed against rat hormone-sensitive lipase, the rate-limiting enzyme in the hydrolysis of the triacylglycerols stored in adipose tissue. Antiserum was obtained after two injections with 20 micrograms enzyme protein, and the immunoglobulin fraction was obtained using a protein G-based solid-phase radioimmunoassay. The hydrolysis of acylglycerols by the enzyme was inhibited by the antibodies, and the enzyme could be efficiently removed from a solution using the antibodies and heat-killed streptococci expressing surface protein G. By Western blot and detection with 125I-protein G, the antibodies were found to selectively bind to hormone-sensitive lipase and to a smaller extent to two minor contaminants, possibly proteolytic fragments of the lipase. The amount of 125I-labelled protein G bound to the lipase on the blot was quantitatively related to the amount of enzyme protein down to the detection limit 10 ng.
 ...
PMID:Use of protein G for preparation and characterization of rabbit antibodies against rat adipose tissue hormone-sensitive lipase. 381 38

The effects of purified salivary lysozyme (HSL) and hen egg white lysozyme (HEWL) on the surface structure of Streptococcus mutans BHT were studied with the aid of scanning electron microscopy. In parallel experiments bacteriolysis was monitored by liberation of 3H-thymidine incorporated into the bacteria. Control cells maintained their shape and had intact cell walls during the experimental period. Exposure of the cells to HSL (5.0 U/ml) or HEWL (5.0 micrograms/ml) for 3 and 18 h resulted in progressive destruction of cell structure. Some cells exhibited ruptures of the cell walls on top of spherical swellings, predominantly located at the ends of the bacteria. After 18 h the majority were disrupted in the septal area leaving numerous empty cup shaped cell walls in the preparations. The findings of the electron microscopic examination were confirmed in the biochemical assay.
 ...
PMID:Scanning electron microscopic study of Streptococcus mutans BHT lysed by lysozyme. 385 24

The effects of propranolol on lipid metabolism were studied in spontaneously hypertensive rats (SHR). Male SHR and corresponding Wistar Kyoto rats (WKY) were used at 5 weeks of age. The SHR were given 10 mg/kg/day of dl-propranolol . HCl by gavage for 10 weeks. Body weight gain in untreated SHR and propranolol-treated SHR (SHR-P) groups were low, as compared with those of the WKY group. Total cholesterol, phospholipid and total lipid of the serum and liver in the SHR-P group were higher than in the SHR group. In the early weeks of treatment, serum triglyceride and non-esterified fatty acid levels in the SHR-P group were slightly lower than those in the SHR group. Aortic lipid levels in the SHR-P group were lower than those in the SHR group. During the later weeks of treatment, blood glucose level in the SHR-P group was higher than in the SHR group. The serum immunoreactive insulin value in the SHR-P group was slightly lower than in the SHR group. These results may suggest that propranolol inhibits hormone-sensitive lipase activity in the early weeks of treatment and influences cholesterol biosynthesis and/or catabolism.
 ...
PMID:Effect of chronic treatment of propranolol on lipid metabolism in spontaneously hypertensive rats (SHR). 389 7


<< Previous 1 2 3 4 5 6 7 8 9 10