Triglycerides, synthesis

A second patent application appeared in 2005, in which a series of pyrrolo[l,2-b]pyridazine-5,6-dicarboxylates was disclosed [31]. Several of the described compounds (exemplified by structure 8) were reported to have IC50 values of 0.5 iM against DGAT-1. Various hydrophobic and amino substitutions at positions 4 and 7, and 2, respectively, were tolerated on the heterocyclic ring, along with heterocyclic replacements for the 6-substituted ethyl carboxylate. 

A series of thiazole-based DGAT-l inhibitors typified by the highly lipophilic compound 10 was disclosed [33]. This report described a tail-vein injection assay wherein a test compound (10, 30, and lOOmg/kg) and 20% emulsion containing a fatty acid mix were orally administered to male C57BL/6N mouse at 0.3ml/mouse. After 1 h following test compound administration, mice were anaesthetized and 

Other related classes of small molecule DGAT-1 inhibitors have appeared [37,38], as well as a set of structures that showed modest pan-inhibition of DGAT-1, DGAT-2, and ACAT2 [39] 

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After each sequence of reactions the acyl group (C4 after one cycle, C6 after two cycles, C8 after three cycles, etc.) re-enters the process at step 3 and undergoes condensation with the next malonyl-CoA. When the final C16 palmitate molecule has been synthesized it is released but needs to be re-activated with CoA, to palmitoyl-CoA for desaturation, elongation into C18 fatty acid molecule or use for triglyceride synthesis (see Figures 6.12, 6.13 and 6.17). 

Dihydroxyacetone phosphate (DHAP) is used in liver and adipose tissue for triglyceride synthesis. 

Figure 1-15-2. Glycerol 3-P Dehydrogenase and Glycerol Kinase in Triglyceride Synthesis and Storage...

Wolfe has presented an excellent description of the systematic application of stable and radioactive isotope tracers in determining the kinetics of intestinal fat absorption, hepatic triglyceride synthesis, lipid mobilization, triglyceride-fatty acid recycling, and cholesterol turnover. 

ACTIN ASSEMBLY KINETICS MICROTUBULE ASSEMBLY KINETICS Triglyceride synthesis kinetics (hepatic), LIRID TRACER KINETICS 2,4,5-Trihydroxyphenylalanine quinone, REDOX-ACTIVE AMINO ACIDS TRIMOLECULAR MOLECUARITY ORDER... 

Il.f.l.1. Insulins. Insulin is the most effective of diabetes medications. Insulin has profound effects on carbohydrate, protein, fat metabolism and electrolytes. It has anabolic and anticatabolic actions. In a state of insulin deficiency, glycogenesis, glucose transport, protein synthesis, triglyceride synthesis, LPL activity in adipose tissue, cellular potassium uptake all decrease on the other hand, gluconeogene-sis, glycogenolysis, protein degradation, ketogene-sis, lipolysis increase. 

Increases triglyceride synthesis and very-low-density lipoprotein formation... 

This is the accumulation of triglycerides in hepatocytes, and there are a number of mechanisms underlying this response as is discussed below (see the sect. "Mechanisms of Toxicity"). The liver has an important role in lipid metabolism, and triglyceride synthesis occurs particularly in zone 3. Consequently, fatty liver is a common response to toxicity, often the result of interference with protein synthesis, and may be the only response as after exposure to hydrazine, ethionine, and tetracycline, or it may occur in combination with necrosis as with carbon tetrachloride. It is normally a reversible response, which does not usually lead to cell death, although it can be very serious as is the case with tetracycline-induced fatty liver in humans. Repeated exposure to compounds, which cause fatty liver, such as alcohol, may lead to cirrhosis. 

Rao, G. A. and Abraham, S. 1975. Stimulatory effect of glucose upon triglyceride synthesis from acetate, decanoate, and palmitate by mammary gland slices from lac-tating mice. Lipids 10, 409-412. 

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