The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function

Flavonoids : old and new aspects of a class of natural therapeutic drugs

Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on the welfare and use of animals in cancer research. All experiments should incorporate the 3Rs: replacement, reduction and refinement. Focusing on animal welfare, we present recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models (e.g., genetically engineered, orthotopic and metastatic); therapy (including drugs and radiation); imaging (covering techniques, anaesthesia and restraint); humane endpoints (including tumour burden and site); and publication of best practice.

/pdf/guidelines-for-the-welfare-and-use-of-animals-in-cancer-zlrmenfril.pdf

Guidelines for the welfare and use of animals in cancer research

Chromatin proteins are covalently modified by at least five different processes; in no case has the precise physiological function been established. One of these post-synthetic, covalent modifications is effected by the enzyme poly(ADP-ribose) polymerase, which uses the coenzyme NAD+ to ADP-ribosylate chromatin proteins. The modification consists largely of mono(ADP-ribose), but long, homopolymer chains of (ADP-ribose) are also present. Various physiological functions have been suggested for (ADP-ribose)n. Here we demonstrate that one function of (ADP-ribose)n is to participate in the cellular recovery from DNA damage. Specific inhibitors of poly(ADP-ribose) polymerase prevent rejoining of DNA strand breaks caused by dimethyl sulphate and cytotoxicity is enhanced thereby. The rejoining of strand breaks is prevented also by nutritionally depleting the cells of NAD.

(ADP-ribose)n participates in DNA excision repair.

https://digitalcommons.andrews.edu/cgi/viewcontent.cgi?article=3516&context=pubs

Health-promoting properties of common herbs

Synchronous behavior pattern of key glycolytic enzymes: Glucokinase, phosphofructokinase, and pyruvate kinase

Increasing concentrations of sodium octanoate were progressively inhibitory to the activities of glucokinase, hexokinase, phosphofructokinase, and pyruvate kinase. Glucose-6-phosphate and 6-phosphogluconate dehydrogenases were also markedly inhibited. Other enzymes of carbohydrate metabolism such as lactate dehydrogenase, phosphohexose isomerase, and fructose-1,6-diphosphatase were not decreased. Among the key glycolytic enzymes, the inhibition of pyruvate kinase by the fatty acid was most marked. The biological significance of the inhibition of the key glycolytic enzymes is interpreted as a feedback inhibitory mechanism in regulation of fatty acid biosynthesis. The mechanism may function for rapid adaptation by which the organism can use the fatty acid level as a metabolic directional switch in decreasing glycolysis and turning on gluconeogenesis.

https://science.sciencemag.org/content/sci/154/3754/1357.full.pdf

Feedback Inhibition of Key Glycolytic Enzymes in Liver: Action of Free Fatty Acids

Regulation of gluconeogenesis and glycolysis: studies of mechanisms controlling enzyme activity.

Insulin secretion induced in vitro by glucose in pancreatic tissue of the rat is unaffected by addition of phloridzin and 3-0-methylglucose to the incubation media, suggesting that the beta-cells are freely permeable to glucose. D-glucosamine and mannoheptulose markedly inhibit the stimulant effect of glucose upon insulin secretion. The inhibitory effect of mannoheptulose is reversible and of the competitive type. Mannoheptulose also competitively inhibits the phosphorylation of glucose by isolated islet homogenates. Phosphorylation of glucose thus appears as a necessary step in the stimulation of insulin secretion by this sugar.

The effect of mannoheptulose on the phosphorylation of glucose and the secretion of insulin by islets of Langerhans

In previous studies, diallyl disulfide induced differentiation in DS19 mouse erythroleukemic cells. A mechanism mediated by increased histone acetylation was investigated. Diallyl disulfide caused increased acetylation of H4 and H3 histones in DS19 cells and K562 human leukemic cells. Diallyl disulfide was more effective than diallyl monosulfide and diallyl sulfone. Acetylation was also induced in rat hepatoma and human breast cancer cells by diallyl disulfide or its metabolite, allyl mercaptan. Allyl mercaptan was a more potent inhibitor of histone deacetylase than diallyl disulfide. Differentiation in erythroleukemic cells by diallyl disulfide and allyl mercaptan may be mediated through induction of histone acetylation.

Michael A. Lea

Papers

Synchronous behavior pattern of key glycolytic enzymes: Glucokinase, phosphofructokinase, and pyruvate kinase

Feedback Inhibition of Key Glycolytic Enzymes in Liver: Action of Free Fatty Acids

Regulation of gluconeogenesis and glycolysis: studies of mechanisms controlling enzyme activity.

The effect of mannoheptulose on the phosphorylation of glucose and the secretion of insulin by islets of Langerhans

Increased acetylation of histones induced by diallyl disulfide and structurally related molecules.