Fatty acids influx

Another observable difference between the diabetic and the fasting state is the high concentration of very low density lipoprotein (VLDL) and chylomicrons in the diabetic and their lowering in the prolonged fasting state. Insulin-dependent lipoprotein lipase is nonfunctional in the diabetic, resulting in an incomplete lipid clearance from the bloodstream. In addition, the liver may not be able to handle the enormous fatty acid influx in the diabetic, converting the excess to VLDL. 

Acetyl-CoA carboxylase is an allosteric enzyme and is activated by citrate, which increases in concentration in the well-fed state and is an indicator of a plentiful supply of acetyl-CoA. Citrate converts the enzyme from an inactive dimer to an active polymeric form, having a molecular mass of several milhon. Inactivation is promoted by phosphorylation of the enzyme and by long-chain acyl-CoA molecules, an example of negative feedback inhibition by a product of a reaction. Thus, if acyl-CoA accumulates because it is not esterified quickly enough or because of increased lipolysis or an influx of free fatty acids into the tissue, it will automatically reduce the synthesis of new fatty acid. Acyl-CoA may also inhibit the mitochondrial tricarboxylate transporter, thus preventing activation of the enzyme by egress of citrate from the mitochondria into the cytosol. 

What effect would the following have on the control of the citric acid cycle (a) a sudden influx of acetyl-CoA from the degradation of fatty acids, and... 

Rigoni M, Caccin P, Gschmeissner S, Koster G, Postle AD et al. (2005) Equivalent effects of snake pla2 neurotoxins and lysophospholipid-fatty acid mixtures. Science 310 1678-80 Rigoni M, Pizzo P, Schiavo G, Weston AE, Zatti G et al. (2007) Calcium influx and mitochondrial alterations at synapses exposed to snake neurotoxins or their phospholipid hydrolysis products. JBiolChem 282 11238-45... 

The effect different fatty acids have on cholesterolemia is well known. Whatever the kind of the effect (hyper- or hypocholesterolemic), it seems to be more pronounced when the fatty acids are esterified at the inner than at the outer positions of TAGs. The lower hypercholesterolemic effect of saturated fatty acids at the outer positions (64) can be the result of a combination of different factors such as reduced absorption by unabsorbable soap formation, which in turn interferes with cholesterol absorption in the intestinal lumen, partial desaturation and oxidation in the small intestinal cells, and reduced targeting into the fiver (63). The stronger hypocholesterolemic effect of polyunsamrated fatty acids at the i -2-position (65) could be the result of increased influx in the liver (66). 

Higher conversion of parent essential fatty acids into their longer and more unsaturated metabolites has been described when the parent essential fatty acids were esterified into the in-2-position (66). This may be explained by increased influx in the liver (66). 

Muitfay M, Rao GH, Robinson P, and Reddy R. (1995). Influx of extracellular calcium and agonist-coupling appear essoitial for the activation of thromboxane AfdepeadeiA phos dK>lipase A human platelets. Prostaglandin Leuk. Essen. Fatty Acids. 53,31-39. 

Liberation of fatty acids induced by phospholipases is connected with a decrease in the pH. We speculate therefore that this change in pH together with the change in cell wall organization induced by lysolecithins may cause the influx of Ca " ions into the cell, where Ca " -ions together with cAMP activate phosphorylation. 

Two widely accepted possible mechanisms for the induction of peroxisome proliferation are (1) activation of specific genes by the chemical or its metabolites, either directly or mediated by a specific receptor, and (2) substrate overload, either as a result of lipolysis occurring outside the liver and causing an influx of fatty acids into the liver or as a consequence of the peroxisome proliferators or their metabolites perturbing lipid metabolism. 

Chow SC, Ansotegui IJ, Jondal M. Inhibition of receptor-mediated calcium influx in T cells by unsaturated non-esterified fatty acids. Biochem J 1990 267 727-732. 

BAT, in its cold/epinephrine-activated state compared to an atrophied or quiescent state, demonstrates increases in blood flow, lipoprotein lipase activity, triacylglycerol synthesis, 5 -deiodinase activity, and triiodothyronine-enhanced UCP gene expression. The processes of fatty acid uptake and triacylglycerol synthesis are essentially the same in both BAT and WAT. However, norepinephrine release by the sympathetic nervous system in acute cold exposure stimulates BAT to enhance expression and secretion of lipoprotein lipase to its sites in the vascular epithelium. Lipoprotein lipase releases fatty acids from passing chylomicrons and very low-density lipoproteins (Chapter 20), causing an influx of fatty acids into the brown adipocytes. 

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