Acid lipase disease

Another example is acid lipase disease, which occurs when the enzyme acid lipase, needed to break down fats, is lacking or missing. The result is a toxic buildup of these fats in cells and tissues. These fatty substances are lipids and include waxes, oils, and cholesterol. 

Wolman s disease Cholesterol ester storage disease Acid lipase Cholesterol ester... 

Cholesterol esters Wolman disease, CESD (cholesterol ester storage disease) Acid lipase 10q23.2-q23.3... 

Once lipoprotein cholesterol enters the cell, the cholesteryl esters are hydrolyzed by lysosomal acid lipase. The lack or malfunction of this enzyme results in intracellular accumulation of cholesterol esters and produces a clinical disorder known as cholesteryl ester storage disease. 

H. Nakagawa, S. Matsubara, M. Kuri-YAMA, H. Yoshidome, J. Fujiyama, H. Yoshida, and M. Osame, Cloning of rat lysosomal acid lipase cDNA and identification of the mutation in the rat model ofWolmaris disease, J. Lipid Res., 1995, 36, 2212-2218. 

Cholesteryl ester storage disease is a less severe form of Wolman syndrome in which a residual amount (1-5%) of lysosomal acid lipase activity is expressed [108,109]. Patients with this disease may survive until young adulthood. 

Acid lipase (EC 3.1.3.2). Hepatic lipase about 25 % of normal. Cholesterol esters deposited in liver, spleen, intestinal mucosa, lymph nodes, aorta. Hepatomegaly, leading to hepatic fibrosis. Sometimes jaundice and/or splenomegaly. Relatively benign. Autosomal recessive. Wolman s disease (below) is probably the expression of a different mutant allele at the same locus. [J. M.Hoeg et al. Amer. J.Hum. Gen. 36 (1984) 1190-1203]... 

Acid lipase (EC 3.1.3.2). Cholesterol esters and triacylglycerols deposited in adrenals, liver, spleen, bone marrow, capillaries, endothelium, ganglion cells of mesenteric plexus and mucosa of small intestine. Plasma lipids mainly normal. Hepatosplenomegaly. Adrenal calcification and enlargement. Failure to thrive in infancy, rapid deterioration and death. Auto-somai recessive. See Cholesterol ester storage disease. 

Lysinuric protein intolerance Hereditary orotic aciduria Pyrimidine-5-nucleotidase def. Familial LCAT def. Wilson disease Acid lipase def. (Wolman disease) 3-Phosphoglycerate dehydrogenase deL Methylentetrahydrofolate reductase def. Methioninsynthase def. 

The anatomic sites (subcellularly) and the details of the enzymatic processes involved in the hydrolysis of chylomicron cholesteryl esters newly taken up by the liver have not been fully defined. It is clear that one of the major processes consists of receptor-mediated endocytosis of chylomicron remnants, followed by hydrolysis of cholesteryl esters and other remnant components within lysosomes. In rare genetic diseases characterized by lysosomal acid lipase deficiency (Wol-man s disease and cholesteryl ester storage disease), cholesteryl esters accumulate in liver cells and in other tissues as well [see Assmann and Frederickson (1983) for review and references]. An acid cholesteryl ester hydrolase from rat liver lysosomes has been partially purified and characterized (Brown and Sgoutas, 1980 Van Berkel etal., 1980). Enzymatic activity was found in preparations of both parenchymal and nonparenchymal liver cells (Van Berkel et al., 1980). Hydrolysis of chylomicron cholesteryl esters taken up by isolated rat hepatocytes was inhibited by chloroquine (Florin and Nilsson, 1977), an agent which inhibits the action of acid hydrolases in lysosomes. Finally, there is also evidence that the rate of cholesteryl ester hydrolysis may be limited by the rate at which internalized remnant particles are moved to the presumably lysosomal site of hydrolysis (Nilsson, 1977 Florin and Nilsson, 1977 Cooper and Yu, 1978). 

Other- Liver disease with impaired hemostasis severe renal disease. Hyperlipidemia Heparin may increase free fatty acid serum levels by induction of lipoprotein lipase. The catabolism of serum lipoproteins by this enzyme produces lipid fragments that are rapidly processed by the liver. Patients with dysbetalipoproteinemia (type III) are unable to catabolize the lipid fragments, resulting in hyperlipidemia. 

Figure 26-18 Exogenous lipoprotein metabolism pathway. TG, Triglyceride CE, cholesterol ester FC, free cholesterol Ft, phospholipids HDL, hIgh-density lipoproteins FA, fatty acid LPL, lipoprotein lipase 6, apolipoprotein B-48 A, apolipoprotein A-i C, apolipoprotein C-ll , apolipoprotein E. (From Rifai N. Lipoproteins and apolipoproteins Composition, metabolism, and association with coronary heart disease. Arch Pathol Lab Med 1986 10 694-701. Copyright 1986, American Medical Association.)...

FAs liberated from food during absorption are metabolized more easily if they are short or medium chain, i.e., C10 or below. The sn-2 monoacylglycerols can be absorbed directly. Therefore, essential or desired FAs are most efficiently utilized from the sn-2 position in acylglycerols. In accordance with this, TAGs with short-chain FAs (SCFAs) or MCFAs at the sn-1 and sn-3 positions and PEFAs at the sn-2 position are rapidly hydrolyzed with pancreatic lipase (sn-1,3-specific lipase) and absorbed efficiently into mucosal cells. SCFAs or MCFAs are used as a source of rapid energy for infants and patients with fat malabsorption-related diseases. LCFAs, especially DHA and arachidonic acid, are important in both the growth and development of an infant, while n-3 PEFAs have been associated with reduced risk of cardiovascular disease in adults (Christensen et al., 1995 Jensen et al., 1995). 

Fatty acid synthase deficiency Tay-Sachs disease Carnitine deficiency Biotin deficiency Lipoprotein lipase deficiency... 

Extensive studies on the endocannabinoid system have revealed a number of cannabinergic proteins involved in the inactivation and biosynthesis of endocannabinoids. These include fatty acid amide hydrolase (FAAH) (Di Marzo et al. 1994 Gaetani et al. 2003 Piomelli et al. 1999), monoglyceride lipase (MAG) (Dinh et al. 2002), and the anandamide transporter (ANT) (Beltramo et al. 1997 Di Marzo et al. 1994 Fegley et al. 2004 Hillard et al. 1997). The above three proteins and the two cannabinoid receptors have received considerable attention and show great promise as potential targets for the development of novel medications for various conditions, including pain, immunosuppression, peripheral vascular disease, appetite enhancement or suppression, and motor disorders. 

---