Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Saturated and monounsaturated fatty acids are mainly synthetized in the brain, but some of them could originate from the diet; in contrast polyunsaturated fatty acids are derived from dietary linoleic and linolenic acid. Saturated fatty acid biosynthesis occurs via three main pathways in mammalian cells. One is de novo synthesis of fatty acids from acetyl-CoA via malonyl-CoA; this system has been isolated in soluble form (the soluble system) from various animal tissues including brain. The second and third pathways involve elongation: in the mitochondrial system, acetyl CoA is the principal substrate in extracts from all organs, even brain; in the microsomal system, however, malonyl-CoA acts as donor of the 2 carbon fragments. In vivo studies in brain have shown that very long chain fatty acids are synthesized by elongation rather than by a than by a de novo mechanism. Feeding animals with oils that have a low n-3 acid content (linolenic series) results in all brain cells and organelles reduced amounts of 22:6 n-3 which is compensated for by an increase in 22:5 n-6. The speed of recuperation from these anomalies is extremely slow for brain cells, organelles and microvessels, in contrast with other organs. Essential fatty acids for the brain could be those with very long chains as shown with cell culture. They are probably synthesized in the liver from linolenic acid. They can also be supplied directly by food. During the period of cerebral development there is a linear relation between the n-3 acid content of the brain and that of food until linolenic acid represents approx. 200 mg per 100 g of food (for 1200 mg linoleic acid). A decrease in acids of the linolenic series in the membranes results in a 40% reduction of Na-K-ATPase in nerve terminals and a 20% reduction in 5'-nucleotidase in whole brain homogenate. A diet low in linolenic acid leads to anomalies in the electroretinogram which disappear partially with age, it seriously affects learning tasks. The presence of linolenic acid in the diet confers a greater resistance to certain neurotoxic agents.
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PMID:Control of brain fatty acids. 207 91

A procedure for the purification of the enzyme bile acid:CoA ligase from guinea pig liver microsomes was developed. Activity toward chenodeoxycholate, cholate, deoxycholate, and lithocholate co-purified suggesting that a single enzyme form catalyzes the activation of all four bile acids. Activity toward lithocholate could not be accurately assayed during the earlier stages of purification due to a protein which interfered with the assay. The purified ligase had a specific activity that was 333-fold enriched relative to the microsomal cell fraction. The purification procedure successfully removed several enzymes that could potentially interfere with assay procedures for ligase activity, i.e. ATPase, AMPase, inorganic pyrophosphatase, and bile acid-CoA thiolase. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis the purified ligase gave a single band of approximately 63,000 Mr. A molecular size of 116,000 +/- 4,000 daltons was obtained by radiation inactivation analysis of the ligase in its native microsomal environment, suggesting that the functional unit of the ligase is a dimer. The purified enzyme was extensively delipidated by adsorption to alumina. The delipidated enzyme was extremely unstable but could be partially stabilized by the addition of phospholipid vesicles or detergent. However, such additions did not enhance enzymatic activity. Kinetic analysis revealed that chenodeoxycholate, cholate, deoxycholate, and lithocholate were all relatively good substrates for the purified enzyme. The trihydroxy bile acid cholate was the least efficient substrate due to its relatively low affinity for the enzyme. Bile acid:CoA ligase could also be solubilized from porcine liver microsomes and purified 180-fold by a modification of the above procedure. The final preparation contains three polypeptides as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The three peptides range in size from 50,000 to 59,000, somewhat smaller than the guinea pig enzyme. The functional size of the porcine enzyme in its native microsomal environment was determined by the technique of radiation inactivation analysis to be 108,000 +/- 5,000 daltons. Thus, the functional form of the porcine enzyme also appears to be a dimer.
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PMID:Bile acid: CoASH ligases from guinea pig and porcine liver microsomes. Purification and characterization. 355 96

Acyl-CoA:cholesterol O-acyltransferase (EC 2.3.1.26) was in microsomal fractions from atherosclerotic rabbit aortic tissue. Activity was increased over 70-fold following 8-11 weeks of cholesterol feeding. Comparison of the lipid composition of aortic microsomal fractions from control and cholesterol-fed animals showed a 2-fold increase in the molar ratio of unesterified cholesterol to phospholipid in the cholesterol-fed group, although no change in phospholipid content or composition was found. Aortic microsomes were fractionated by sucrose density gradient centrifugation. Acyl-CoA:cholesterol O-acyltransferase was localized in fractions containing neutral alpha-glucoside activity but was clearly separated from 5'-nucleotidase activity. The cholesteryl ester formed during in vitro incubation of incubations of microsomes with either [1-14C]-oleoyl CoA or [7-3H]cholesterol was localized in the same region of the density gradient as acyl-CoA:cholesterol O-acyltransferase. The studies indicate that the increased acyl-CoA:cholesterol O-acyltransferase activity found in cells from aortic atherosclerotic lesions is due to both an increased amount of enzyme and to an expanded pool of microsomal cholesterol which is available for esterification.
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PMID:Properties of acyl-CoA:cholesterol O-acyltransferase in aortic microsomes from atherosclerotic rabbits. 737 Feb 90

Narcolepsy is a chronic sleep disorder with a yet unknown cause, but the specific loss of hypocretin-producing neurons together with a strong human leukocyte antigen (HLA) association has led to the hypothesis that autoimmune mechanisms might be involved. Here, we describe an extensive effort to profile autoimmunity repertoires in serum with the aim to find disease-related autoantigens. Initially, 57 serum samples from vaccine-associated and sporadic narcolepsy patients and controls were screened for IgG reactivity towards 10 846 fragments of human proteins using planar microarrays. The discovered differential reactivities were verified on suspension bead arrays in the same sample collection followed by further investigation of 14 antigens in 176 independent samples, including 57 narcolepsy patients. Among these 14 antigens, methyltransferase-like 22 (METTL22) and 5'-nucleotidase cytosolic IA (NT5C1A) were recognized at a higher frequency in narcolepsy patients of both sample sets. Upon sequence analysis of the 14 proteins, polymerase family, member 3 (PARP3), acyl-CoA-binding domain containing 7 (ARID4B), glutaminase 2 (GLS2) and cyclin-dependent kinase-like 1 (CDKL1) were found to contain amino acid sequences with homology to proteins found in the H1N1 vaccine. These findings could become useful elements of further clinical assays that aim towards a better phenotypic understanding of narcolepsy and its triggers.
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PMID:Autoantibody targets in vaccine-associated narcolepsy. 2720 86