Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of ciprofibrate, a hypolipidemic drug, was examined in the metabolism of palmitic (C16:0) and lignoceric (C24:0) acids in rat liver. Ciprofibrate is a peroxisomal proliferating drug which increases the number of peroxisomes. The palmitoyl-CoA ligase activity in peroxisomes, mitochondria and microsomes from ciprofibrate treated liver was 3.2, 1.9 and 1.5-fold higher respectively and the activity for oxidation of palmitic acid in peroxisomes and mitochondria was 8.5 and 2.3-fold higher respectively. Similarly, ciprofibrate had a higher effect on the metabolism of lignoceric acid. Treatment with ciprofibrate increased lignoceroyl-CoA ligase activity in peroxisomes, mitochondria and microsomes by 5.3, 3.3 and 2.3-fold respectively and that of oxidation of lignoceric acid was increased in peroxisomes and mitochondria by 13.4 and 2.3-fold respectively. The peroxisomal rates of oxidation of palmitic acid (8.5-fold) and lignoceric acid (13.4-fold) were increased to a different degree by ciprofibrate treatment. This differential effect of ciprofibrate suggests that different enzymes may be responsible for the oxidation of fatty acids of different chain length, at least at one or more step(s) of the peroxisomal fatty acid beta-oxidation pathway.
Mol Cell Biochem 1991 Feb 02
PMID:Effect of ciprofibrate on the activation and oxidation of very long chain fatty acids. 200 77

Rabbit aortic smooth muscle cells take up lipid droplets when they are presented using an inverted culture technique. These droplets were localized in secondary lysosomes as demonstrated by staining for acid phosphatase. Initially, 69% of the cell volume was occupied by lipid, and 94% of the lipid was in lysosomes. After a 24-hr clearance period, the cell volume occupied by lipid decreased to 53%, although there was no change in the fraction of cell lipid that was in lysosomes. To confirm that hydrolysis of droplet lipid was occurring in lysosomes, cultures were exposed to medium containing Sandoz 58-035, an inhibitor of acyl CoA:cholesterol acyl transferase, for 24 hr in the presence and absence of chloroquine, ammonium chloride, or methylamine. Although the hydrolysis of cholesteryl oleate was sensitive to these lysosomotropic agents, the hydrolysis of triolein was not. Using reconstituted LDL containing cholesteryl oleate and triolein, we demonstrated that the hydrolyses of cholesteryl oleate and triolein were equally sensitive to the lysosomotropic agents when the cells were not loaded with droplet lipid. However, in cells loaded with lipid, hydrolysis of LDL cholesteryl ester was sensitive to the lysosomotropic agents but hydrolysis of triolein was not. We therefore conclude that both droplet lipids were hydrolyzed in lysosomes, and we attribute the failure of the lysosomotropic agents to inhibit fully the hydrolysis of droplet triolein to the presence of a large mass of free fatty acids in the lysosome that maintains a sufficiently low pH to sustain the triglyceridase activity, but not the cholesteryl esterase activity, of the lysosomal acid lipase.
Exp Mol Pathol 1991 Apr
PMID:Lysosomal hydrolysis of lipids in a cell culture model of smooth muscle foam cells. 202 36

The metabolism of biogenic amines by the filarial worm, Brugia pahangi, was investigated by incubating cut worms with radio-labelled amine substrates. Two-dimensional thin-layer chromatography and analysis on two high-performance liquid chromatography systems showed that [14C]5-hydroxytryptamine was metabolised to a less polar compound that was identified as N-acetyl 5-hydroxytryptamine. N-Acetyloctopamine and N-acetyldopamine were also formed when cut B. pahangi were incubated with [14C]octopamine and [3H]dopamine, respectively. N-Acetyltransferase activity towards 5-hydroxytryptamine was readily detected in nematode homogenates. This enzyme was localised in a 50,000 x g supernatant and required the addition of the co-substrate, acetyl CoA, for activity. No evidence was obtained for the involvement of monoamine oxidases in the metabolism of 5-HT in these filarial worms.
Mol Biochem Parasitol 1990 Dec
PMID:N-acetylation of serotonin, octopamine and dopamine by adult Brugia pahangi. 209 Sep 41

The presence of redox systems in microsomes of brown adipose tissue (BAT) in cold exposed rats was investigated and compared with liver. BAT microsomes showed high activity of lipid peroxidation measured both by the formation of malondialdehyde (MDA) and by oxygen uptake. NADH and NADPH dependent cytochrome c reductase activity were present in both BAT and liver microsomes. Aminopyrine demethylase and aniline hydroxylase activities, the characteristic detoxification enzymes in liver microsomes could not be detected in BAT microsomes. BAT minces showed very poor incorporation of [1-14C]acetate and [2-14C]mevalonate in unsaponifiable lipid fraction compared to liver. Biosynthesis of cholesterol and ubiquinone, but not fatty acids, and the activity of 3-hydroxy-3-methyl glutaryl CoA reductase appear to be very low in BAT. Examination of difference spectra showed the presence of only cytochrome b5 in BAT microsomes. In addition to the inability to detect the enzyme activities dependent on cytochrome P-450, a protein with the characteristic spectrum, molecular size in SDS-PAGE and interaction with antibodies in double diffusion test, also could not be detected in BAT microsomes. The high activity of lipid peroxidation in microsomes, being associated with large oxygen uptake and oxidation of NADPH, will also contribute to the energy dissipation as heat in BAT, considered important in thermogenesis.
Mol Cell Biochem 1990 Feb 09
PMID:Microsomal redox systems in brown adipose tissue: high lipid peroxidation, low cholesterol biosynthesis and no detectable cytochrome P-450. 210 21

Previous studies have shown that dietary provision of carbohydrate can alter cardiac isomyosin distribution in hormonally deficient rats. The main objective of this study was to determine if varying the heart's potential to utilize carbohydrate for energy provision can influence the cardiac isomyosin expression in normal weanling rats. Animals were assigned to one of five groups according to dietary and/or metabolic treatment: (1) mixed-control--(M); (2) high carbohydrate--(H); (3) low carbohydrate--(L); (4) mixed-diet supplemented with oxfenicine, a cardiospecific fatty acid oxidation inhibitor--(MO); and (5) high carbohydrate diet supplemented with oxfenicine--(HO). The results show that 4 weeks of dietary manipulations aimed to either increase or decrease carbohydrate supply to the heart, failed to induce any alterations in either cardiac myosin ATPase activity or isoenzyme pattern. However, extremes in carbohydrate provision altered the metabolic properties of both heart and skeletal muscle. A low carbohydrate diet increased 3-hydroxyacyl CoA dehydrogenase (P less than 0.05) and citrate synthase activities (P less than 0.05) and decreased glycogen content in both heart and soleus muscle; whereas, a high carbohydrate diet, in conjunction with oxfenicine, tended to increase hexokinase activity in these same tissues. These alterations provide indirect evidence that the contributions of both fat and carbohydrate to the energy balance of the heart and skeletal muscle were altered by the imposed dietary interventions. Collectively, these results suggest that although the substrate utilization patterns of the normal weanling heart can be modified via dietary manipulation, such shifts do not exert any regulatory influence on cardiac isomyosin expression.
J Mol Cell Cardiol 1990 Mar
PMID:Dietary effects on cardiac metabolic properties in rodents. 214 63

The penDE gene encoding acyl-CoA:6-amino penicillanic acid acyltransferase (AAT), the last enzyme of the penicillin biosynthetic pathway, has been cloned from the DNA of Aspergillus nidulans. The gene contains three introns which are located in the 5' region of the open reading frame. It encodes a protein of 357 amino acids with a molecular weight of 39,240 Da. The penDE gene of A. nidulans shows 73% similarity at the nucleotide level with the penDE gene of Penicillium chrysogenum. The A. nidulans gene was expressed in P. chrysogenum and complemented the AAT deficiency of the non-producer mutants of P. chrysogenum, npe6 and npe8. The penDE gene of A. nidulans is linked to the pcbC gene, which encodes the isopenicillin N synthase, as also occurs in P. chrysogenum. Both genes show the same orientation and are separated by an intergenic region of 822 nucleotides.
Mol Gen Genet 1990 May
PMID:Cloning, characterization of the acyl-CoA:6-amino penicillanic acid acyltransferase gene of Aspergillus nidulans and linkage to the isopenicillin N synthase gene. 216 27

The mechanism of transfer of long chain fatty acids across the myocardial sarcolemmal membrane was investigated in isolated, calcium-resistant, rat cardiomyocytes. The initial rate of 14C-palmitate uptake was determined at constant and increasing palmitate/albumin ratios. The latter condition led to a saturable dependence of uptake rate on palmitate concentration. At a constant palmitate/albumin ratio however, there was an almost constant rate of uptake even though the absolute concentration of palmitate increased. The enhanced metabolic rate resulting from electrically induced contractions of the myocytes decreased the apparent Km of uptake from 62 to 23 microM. Thirty seconds after administration, there was no further increase in the [14C]palmitate content of the myocytes. Moreover, from experiments using ghost membrane vesicles the concentration of palmitate in membranes increased almost linearly with increasing palmitate/albumin ratios. This concentration remained virtually constant if vesicles were pre-treated with diamide. Our results do not support the concept of an albumin receptor-mediated uptake but rather suggest that fatty acids are incorporated into cardiomyocytes by a simple diffusion process which is not rate-limiting. The rate of uptake is influenced both by the metabolic rate and by the concentration of fatty acids in the membranes. The rate-limiting step of fatty acid uptake is probably either the formation of acyl-CoA catalyzed by the membrane associated acyl-CoA synthetase, or the transfer of fatty acid carnitine esters across the mitochondrial matrix membrane.
J Mol Cell Cardiol 1990 Aug
PMID:Sarcolemmal fatty acid transfer in isolated cardiomyocytes governed by albumin/membrane-lipid partition. 217 57

Hepatic-FABP was labelled at cysteine-69 with the fluorescent environmentally sensitive reporter group AEDANS. The labelled protein had an emission maximum at 465 nm indicating that cysteine-69 was buried in a non-polar environment. The modified protein was still able to bind ligands such as oleic acid, oleoyl CoA and haem. The affinity of AEDANS-FABP for haem was unaltered as compared with the native protein indicating that cysteine-69 must be remote from the ligand binding site. The binding of oleic acid did not significantly perturb the fluorescence emission spectrum of the fluorescent reporter group suggesting that there are not large conformational changes in the region of cysteine-69 on fatty acid binding. The binding of stoichiometric amounts of oleoyl CoA was accompanied by a small fluorescence enhancement which suggests that fatty acyl CoAs may interact with other regions of the FABP molecule not involved in fatty acid binding.
Mol Cell Biochem
PMID:The chemical modification of cysteine-69 of rat liver fatty acid-binding protein (FABP): a fluorescence approach to FABP structure and function. 226 55

Although abundant in most biological tissues and chemically well characterized, the fatty acid-binding protein (FABP) was until recently in search of a function. Because of its strong affinity for long chain fatty acids and its cytoplasmic origin, this protein was repeatedly claimed in the literature to be the transcytoplasmic fatty acid carrier. However, techniques to visualize and quantify the movements of molecules in the cytoplasm are still in their infancy. Consequently the carrier function of FABP remains somewhat speculative. However, FABP binds not only fatty acids but also their CoA and carnitine derivatives, two typical molecules of mitochondrial origin. Moreover, it has been demonstrated and confirmed that FABP is not exclusively cytoplasmic, but also mitochondrial. A function for FABP in the mitochondrial metabolism of fatty acids plus CoA and carnitine derivatives would therefore be anticipated. Using spin-labelling techniques, we present here evidence that FABP is a powerful regulator of acylcarnitine flux entering the mitochondrial beta-oxidative system. In this perspective FABP appears to be an active link between the cytoplasm and the mitochondria, regulating the energy made available to the cell. This active participation of FABP is shown to be the consequence of its gradient-like distribution in the cardiac cell, and also of the coexistence of multispecies of this protein produced by self-aggregation.
Mol Cell Biochem
PMID:Role of fatty acid-binding protein in cardiac fatty acid oxidation. 226 57

Acyl-CoA-binding protein is a 10 Kd protein which binds medium- and long-chain acyl-CoA esters with high affinity. The concentration in liver is 2-4 times the acyl-CoA concentration. ACBP has much greater affinity for acyl-CoA than FABP. FABP from bovine heart and liver is unable to compete with multilamellar liposomes, Lipidex and microsomal membrane in binding acyl-CoA esters, whereas ACBP effectively extracts acyl-CoA from all those sources. Previously published results on the effect of FABP on acyl-CoA metabolism need to be reevaluated due to possible contamination with ACBP. Recently it was discovered that ACBP is identical to a putative neurotransmitter diazepam binding inhibitor. The possibility therefore exists that ACBP has more than one function.
Mol Cell Biochem
PMID:Acyl-CoA-binding protein (ACBP) and its relation to fatty acid-binding protein (FABP): an overview. 226 62


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