Lipids peroxisomes

Reddy JK, Mannaerts GP Peroxisomal lipid metabolism. Annu RevNutr 1994 14 343. 

Hepatic peroxisome proliferation, characterized by liver enlargement due to hyperplasia and hypertrophy, has been proposed as a basis for differences in species susceptibility to trichloroethylene carcinogenicity. Peroxisomes are membrane-bound organelles which contain enzymes generally involved in lipid metabolism. 

With the exception of the acetyl-CoA thiolase, all these enzymes are located exclusively in the peroxisomes, whereas the enzymes that are involved in lipid synthesis are found in the microsomes and the mitochondrion. 

In their review some years ago, Reddy and Rao (1986) cited several lines of evidence for peroxisome-proliferation-mediated oxidative stress being associated with hepatocarcinogenesis. They mentioned the sustained increase in hydrogen peroxide production, the detectable increased levels of hydrogen peroxide in the livers of treated animals, increased lipid peroxidation associated with treatment and marked inhibition of hepatocarcinogenesis by antioxidant compounds. However, definitive studies remain to be carried out. 

Peroxisome-proliferator activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARa is implicated in the regulation of lipid metabolism, lipoprotein synthesis, and inflammatory response in liver and other tissues. 

Hajra, A. K. Glycerolipid biosynthesis in peroxisomes (microbodies). Prog. Lipid Res. 34 343-364,1995. 

Familial demyelinative/dysmyelinative neuropathies may be caused by impaired peroxisomal lipid metabolism. 

Other leukodystrophies are associated with the lysosomal and peroxisomal disorders in which specific lipids or other substances accumulate due to a deficiency in a catabolic enzyme - for example Krabbe s disease, meta-chromatic leukodystrophy (MLD) and adrenoleuko-dystrophy (ALD) [1,2]. (These are discussed in detail in Ch. 40.) Similarly, disorders of amino acid metabolism can lead to hypomyelination - for example phenylketonuria and Canavan s disease (spongy degeneration) [1, 2, 25] (Ch. 40). The composition of myelin in the genetically... 

Fatty acid utilized by muscle may arise from storage triglycerides from either adipose tissue depot or from lipid stores within the muscle itself. Lipolysis of adipose triglyceride in response to hormonal stimulation liberates free fatty acids (see Section 9.6.2) which are transported through the bloodstream to the muscle bound to albumin. Because the enzymes of fatty acid oxidation are located within subcellular organelles (peroxisomes and mitochondria), there is also need for transport of the fatty acid within the muscle cell this is achieved by fatty acid binding proteins (FABPs). Finally, the fatty acid molecules must be translocated across the mitochondrial membranes into the matrix where their catabolism occurs. To achieve this transfer, the fatty acids must first be activated by formation of a coenzyme A derivative, fatty acyl CoA, in a reaction catalysed by acyl CoA synthetase. 

Peroxisome proliferator-activated receptors (PPARs) PPREs Regulate multiple aspects of lipid metabolism Activated by fibrates and thiazolidinediones Zinc finger... 

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that bind to DNA response elements (PPREs) and control multiple aspects of lipid metabolism. Individual members of this family of zinc-finger proteins are activated by a variety of natural and xenobiotic dgands, including ... 

ASBT has a complex regulatory system reflecting the importance of this transporter to bile-acid pool size and bile-acid synthesis rates. Hepatic nuclear factor la (HNF-la) is necessary for expression of ASBT as knockout mice showed no expression and had defective bile-acid transport.Conversely, FXR-null mice showed no difference in expression of ASBT, showing that FXR plays no part in regulation of ASBT. In man, HNF-la controls baseline promoter activity of the ASBT gene as the minimal construct with full promoter activity was found to have 3 HNF-la binding sites. These authors also showed that the promoter construct bound peroxisome proliferator activated receptor a (PPARa)/9 cis retinoic acid receptor heterodimer, demonstrating a link between bile-acid absorption and hepatic lipid metabolism mediated by PPARa. 

Sharma AM, Staels B. Review peroxisome proliferator-activated receptor y and adipose tissue - understanding obesity-related changes in regulation of lipid and glucose metabolism. J Clin Endocrinol Metab 2007 92 386-95. 

Ruyter B., O. Andersen, A. Dehli, A.-K. Ostlrmd Farrants, T. Gjoen, and M.S. Thomassen (1997). Peroxisome proliferator activated receptors in Atlantic salmon Salmo solar)-. Effects on PPAR transcription and acyl-CoA oxidase activity in hepatocytes by peroxisome proliferators and fatty acids. BBA-Lipids and Lipid Metabolism 1348 331-338. 

The 3,4-dihydro-22/-l,3-benzoxazin-4-one derivative DRF-2519 587, bearing a 2,4-thiazolidinedione moiety in the side chain attached to the nitrogen atom, proved to be an activator of the a- and y-types of the peroxisome proliferator-activated receptors (PPAR-a and -7), which endowed it with antidiabetic and hypolipidemic potential. Compound 587 demonstrated significant plasma glucose-, insulin-, and lipid-lowering activity in mice and improvement in lipid parameters in fat-fed rats <2006BMC584>. 

Elliott, B.M. Elcombe, C.R. (1987) Lack of DNA damage or lipid peroxidation measured in vivo in the rat liver following treatment with peroxisomal proliferators. Carcinogenesis, 8, 1213-1218... 

Kombrast, D.J., Barfknecht, T.R. Ingram, P. (1984) Effect of di(2-ethylhexyl)phthalate on DNA repair and lipid peroxidation in rat hepatocytes and on metabolic cooperation in Chinese hamster V-79 cells. J. Toxicol, environ. Health, 13, 99-116 Kurata, Y., Kidachi, F., Yokoyama, M., Toyota, N., Tsuchitani, M. Katoh, M. (1998) Subchronic toxicity of di(2-ethylhexyl)phthalate in common marmosets lack of hepatic peroxisome proliferation, testicular atrophy, or pancreatic acinar cell hyperplasia. Toxicol. Sci., 42, 49-56... 

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