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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At least three different proteins are implicated in the cellular transport of fatty acid moieties: a plasmalemmal membrane and a cytoplasmic fatty acid-binding protein (FABPPM and FABPC, respectively) and cytoplasmic acyl-CoA binding protein (ACBP). Their putative main physiological significance is the assurance that long-chain fatty acids and derivatives, either in transit through membranes or present in intracellular compartments, are largely complexed to proteins. FABPC distinguishes from the other proteins in that distinct types of FABPC are found in remarkable abundance in the cytoplasmic compartment of a variety of tissues. Although their mechanism of action is not yet fully elucidated, current knowledge suggests that the function of this set of proteins reaches beyond simply aiding cytoplasmic solubilization of hydrophobic ligands, but that they can be assigned several regulatory roles in cellular lipid homeostasis.
Mol Cell Biochem
PMID:Cellular fatty acid-binding proteins: current concepts and future directions. 226 65

A cytosolic protein, able to facilitate intermembrane movements of phospholipids in vitro, has been purified to homogeneity from sunflower seedlings. This protein, which has the properties of a lipid-transfer protein (LTP), is also able to bind oleoyl-CoA, as shown by FPLC chromatography. This finding, in addition to previous observations suggesting that a lipid-transfer protein from spinach leaves can bind oleic acid and that oat seedlings contain a fatty acid-binding protein with similar features than lipid transfer proteins, provides a clear demonstration that plant cells contain bifunctional fatty acid/lipid transfer proteins. These proteins can play an active role in fatty acid metabolism which involves movements of oleyl-CoA between intracellular membranes.
Mol Cell Biochem
PMID:Bifunctional lipid-transfer: fatty acid-binding proteins in plants. 226 69

In the presence of Mg2+, pure glutamate dehydrogenase is more reactive with NADPH than with NADH and is markedly activated by elevations in the ADP/ATP ratio or the addition of leucine. Because these are properties of glutamate dehydrogenase in mitochondria but not properties of the pure enzyme studied in the absence of Mg2+, Mg2+ could be a ligand that confers upon glutamate dehydrogenase the regulatory properties of this enzyme found in situ. In the absence of the allosteric activators ADP, leucine, or succinyl-CoA, Mg2+ is an inhibitor and increases product inhibition by alpha-ketoglutarate in the forward reaction and substrate inhibition by alpha-ketoglutarate in the reverse reaction. However, the allosteric activators convert Mg2+ from an inhibitor into an activator of the forward reaction. In the reverse reaction, ADP also converts Mg2+ from an inhibitor into an activator and leucine eliminates inhibition by Mg2+. Because Mg2+ is an inhibitor in the absence of activator that also increases inhibition by alpha-ketoglutarate, whereas in the presence of activator Mg2+ has no effect or is itself an activator, Mg2+ magnifies the effect of the activator, and magnification increases with increases in the concentration of alpha-ketoglutarate. Leucine and its analog 2-aminobicyclo (2.2.1) heptane 2-carboxylic acid (BCH) have almost identical effects on both human and bovine glutamate dehydrogenase in both the presence and absence of Mg2+. However, advantages of BCH over leucine as a potential pharmacological activator of glutamate dehydrogenase are that BCH is not metabolized and, unlike leucine, BCH does not inhibit ornithine transcarbamylase. Isoleucine and valine alone have little effect on human glutamate dehydrogenase, but isoleucine slightly inhibits the enzyme in the presence of leucine.
Mol Pharmacol 1990 Jun
PMID:Regulation of glutamate dehydrogenase by Mg2+ and magnification of leucine activation by Mg2+. 235 6

Insertion of the fusion-generating phage Mud1 (Ap, lacZ) yielded two similar isolates, DC511 and DC512, which were unable to grow aerobically on acetate or alpha-ketoglutarate but which could use succinate, malate, fumarate, glycerol, and various sugars. These mutants were unable to grow anaerobically on most sugars unless provided with methionine, lysine, and delta-aminolevulinic acid, all of which require succinyl-CoA for their synthesis. The insertions of both mutants mapped at 17 min, in the suc operon. Enzyme assays indicated a lack of succinyl-CoA synthetase; however, full activity of the alpha-ketoglutarate dehydrogenase was retained. Beta-galactosidase expression by strains containing these gene fusions was reduced under anaerobic conditions. In aerobically grown cultures, both fusions were induced about fivefold in the presence of acetate. This type of regulation would be expected of a Krebs cycle enzyme.
Mol Gen Genet 1989 Jan
PMID:Anaerobic growth defects resulting from gene fusions affecting succinyl-CoA synthetase in Escherichia coli K12. 249 97

Two genes, pcbC and penDE (also named ips and aat, respectively) encoding the enzymes isopenicillin N synthase and acyl-CoA:6-amino penicillanic acid (6-APA) acyltransferase, which are involved in the penicillin biosynthetic pathway in Penicillium chrysogenum, were cloned. Both genes are clustered together in a 5.1 kb SalI DNA fragment and are separated by a nontranscribed intergenic region of 1.5 kb. These genes are transcribed from different promoters in two separate transcripts of about 1.15 kb each. The penDE gene complements mutants of P. chrysogenum deficient in acyltransferase and the pcbC gene increases the level of isopenicillin N synthase in strains containing low levels of this enzyme. The clustering of penicillin biosynthetic genes is of great interest in the light of previous claims of horizontal transfer of the pcbC gene from beta-lactam producing Streptomyces to filamentous fungi.
Mol Gen Genet 1989 Sep
PMID:Two genes involved in penicillin biosynthesis are linked in a 5.1 kb SalI fragment in the genome of Penicillium chrysogenum. 251 25

In-vitro translation of anglerfish islet mRNA revealed three glucagon precursors (preproglucagons): one with Mr 16,000 and two with Mr 14,000. The two Mr 14,000 precursors were well separated upon isoelectric focusing gels (pI values of 7.2 and 7.3), but had identical peptide maps. Translation of hybrid-selected Mr 14,000 preproglucagon mRNA in the presence of microsomal vesicles revealed that both precursors were processed to the same proglucagon. Northern blot analysis detected two mRNA species encoding Mr 14,000 precursor. A full-length Mr 14,000 preproglucagon cDNA was subcloned into a transcription vector, and coupled in-vitro transcription-translation was performed; surprisingly, both Mr 14,000 precursors were synthesized. To test whether acetylation of the free amino terminus generated the more acidic precursor, acetylase activity was partially inactivated with the inhibitor S-acetonyl-CoA, and acetyl-CoA was depleted by addition of oxaloacetate and citrate synthetase. Under these conditions, the level of the most basic preproglucagon was greatly enhanced, but when exogenous acetyl-CoA was added, the acidic form predominated. We conclude that acetylation generates the acidic precursor, and we discuss the implications of our findings for the biogenesis of other peptide hormones.
J Mol Endocrinol 1989 Mar
PMID:In-vitro biosynthesis of multiple preproglucagons results from acetylation of the primary translation products. 267 84

Translocation of lipids inside mammalian cells is considered to be facilitated by a number of low-molecular weight lipid binding proteins. An overview of these proteins is given, with particular reference to the heart. Three distinct phospholipid transfer proteins specifically stimulate the net transfer of individual phospholipid classes between membrane structures. In rat cardiac muscle their content is 15-140 pmol/g ww. Fatty acid-binding proteins (FABP) are abundantly present in tissues actively involved in the uptake or utilization of long-chain fatty acids, such as intestine, liver and heart. The four distinct FABP types now identified show a complex tissue distribution with some tissues containing more than one type. Heart (H-) FABP comprises about 5% of the cytosolic protein mass; its content in rat heart is 100 nmol/g ww. Immunochemical evidence has been obtained for the presence of H-FABP in several other tissues, including red skeletal muscle, mammary gland and kidney. Beside long-chain fatty acids FABP binds with similar affinity also fatty acyl-CoA and acyl-L-carnitines. In heart the latter compound may be the primary ligand, since normoxic acyl-L-carnitine levels are several fold higher than those of fatty acids. In addition, H-FABP was found to modulate cardiac energy production by controlling the transfer of acyl-L-carnitine to the mitochondrial beta-oxidative system. H-FABP may also protect the heart against the toxic effects of high intracellular levels of fatty acid intermediates that arise during ischemia.
Mol Cell Biochem
PMID:Intracellular transport of lipids. 267 66

We have constructed hybrid dihydrofolate reductase (DHFR) genes which are controlled by the sterol-responsive hamster 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase promoter. Stable transfection frequencies of these chimeric templates into a DHFR-deficient Chinese hamster cell line indicate that the HMG CoA reductase promoter fragment confers DHFR transformation irrespective of its orientation relative to a downstream murine DHFR cDNA. Sterol-regulated levels of DHFR RNA and protein are detected from hybrid genes which carry a properly oriented promoter fragment. Constructions which invert this HMG CoA reductase promoter, however, generate DHFR RNA levels which do not respond to sterols. In the context of these transfected fusion genes, we present evidence of divergent opposite-strand transcription initiating from the HMG CoA reductase 5' fragment. In contrast, the endogenous HMG CoA reductase promoter region shows no apparent evidence of such bidirectional activity.
Mol Cell Biol 1989 Feb
PMID:Chimeric 3-hydroxy-3-methylglutaryl coenzyme A reductase-dihydrofolate reductase genes display bidirectional expression and unidirectional regulation in stably transfected cells. 271 Jan 19

Regulation of beta-oxidation under various metabolic conditions and energy loads was studied by employing a newly developed method for assaying 3-hydroxyacyl-CoA and 2-trans-enoyl-CoA intermediates of fatty acid oxidation. A 66% inhibition of oleate oxidation with a concomitant 68% inhibition of oxygen consumption resulted in a 81% decrease in the carnitine/acyl-carnitine ratio, but the concentrations of 2-trans-enoyl-CoA and 3-hydroxyacyl-CoA esters did not change significantly and the acid-insoluble acyl-CoA content did not change. The acetyl-CoA concentration increased three-fold, however, and there was a simultaneous tendency for the NADH/NAD+ ratio to shift towards oxidation. The results suggest that the main regulatory site of fatty acid oxidation resides at an early step in the pathway. Since the concentrations of the acyl-CoA derivatives identified did not undergo major changes even though the acyl-carnitine concentration changed some rate limitation must already occur at the steps of acyl transport into the mitochondria or the carnitine acyltransferase II.
J Mol Cell Cardiol 1989 Aug
PMID:Energy-linked regulation of mitochondrial fatty acid oxidation in the isolated perfused rat heart. 277 13

The energy-linked processes (transmembrane potential and oxidative phosphorylation) resulted in impaired mitochondria isolated from ischemic perfused rat hearts. Addition of 1.5 mM L-propionyl-carnitine to the perfusate significantly reduced the ischemic damage and ameliorated mitochondrial Ca2+ homeostasis. In both normoxic and ischemic hearts perfused with L-propionyl-carnitine a consistent amount of propionyl-CoA-otherwise undetectable-was produced. L-propionyl-carnitine treatment also prevented the decrease of succinyl-CoA associated with the ischemic condition. These results and the decrease of myocardial acetyl-CoA induced by exogenous L-propionyl-carnitine points to the anaplerotic effect of this ester. The consequently improved flux in the tricarboxylic-acid cycle may account for the observed protection of mitochondrial functions afforded by L-propionyl-carnitine in the ischemic perfused hearts.
Mol Cell Biochem
PMID:L-propionyl-carnitine protection of mitochondria in ischemic rat hearts. 277 36


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