Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The liver cells lose the major part of their carnitine during the commonly used isolation procedure by the collagenase-perfusion method. 2. The cells take up carnitine and the carnitine precursor butyrobetaine when these substances are added to the medium. The carnitine content of isolated liver cells can increase to about 15 mM with no apparent harm to the cells. 3. The data indicate the existence of a common carrier in the plasma membrane which mediates the uphill transport of both carnitine and butyrobetaine. The carrier has a high affinity for butyrobetaine (Km=0.5 mM) and a lower one for carnitine (Km=5.6 mM). 4. The intracellular butyrobetaine is hydroxylated to carnitine with a rate of approximately 0.33 mumol-g wet weight-1-h-1 which is sufficient to cover the turn over of carnitine in the whole rat. Carnitine is effectively esterified in the liver cells to acetylcarnitine and long-chain acylcarnitines. 5. Both carnitine and acetylcarnitine are released from the cells. The release of both compounds is probably physiological since it was found that acetylcarnitine constitutes a similar fraction of the total acid soluble carnitine both in the blood and liver of the intact rat.
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PMID:Active transport of butyrobetaine and carnitine into isolated liver cells. 97 47

Palmitate oxidation in rat skeletal muscle was investigated with a suspension of intact isolated cells. M. flexor digitorum brevis was dissociated by a 6 h collagenase treatment to yield single myofibers of which 76% were viable. The contributions of 14CO2 and 14C-labeled acid-soluble intermediates to total oxidation products from palmitate were evaluated. The myofiber suspension exhibited a higher total oxidation rate than the isolated whole muscle, due to improved transport of palmitate to the sarcolemma. Addition of cytoplasmic cofactors L-carnitine, CoASH and ATP did not increase the palmitate oxidation. 14CO2 amounted to about 37% of oxidation products. With [1(-14)C]- and [16(-14)C]palmitate, the oxidation rates were equal. These findings indicate that the cellular integrity was well preserved. The oxidation rates were sharply decreased in fibers with damaged sarcolemmas, and in intact fibers when rotenon and antimycin A were applied. The damaged fibers restored the production of acid-soluble intermediates in the presence of cofactors. The results indicate that suspended skeletal myofibers are an adequate in vitro system for measurements of metabolic activities in the resting muscle.
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PMID:Palmitate oxidation in suspended skeletal muscle fibers from the rat. 609 70

Carnitine-mediated prevention of ethanol-induced hepatic steatosis is related to the attenuation of ethanol metabolism by carnitine in the intact rat. Although carnitine retards ethanol oxidation in the intact animal, the in vitro activities of ethanol-metabolizing enzymes remain unaltered. Therefore, hepatocytes were targeted to understand the mechanism of carnitine effect on ethanol metabolism. Rat hepatocytes were isolated by a collagenase-perfusion technique and incubated in albumin-containing medium with ethanol in the presence or absence of added carnitine or related compounds. Ethanol oxidation was determined by the loss of ethanol as well as by the products formed. The rate of ethanol oxidation in the presence of carnitine was one-half the rate in the absence of carnitine (14 vs. 25 nmol.min-1.million-1 cells). It took 100 times the concentration of carnitine to equal the maximal inhibition produced by acetylcarnitine and the effect of acetylcarnitine was without a lag time. It is concluded that acetylcarnitine is the mediator of carnitine inhibition of ethanol oxidation.
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PMID:Acetylcarnitine-mediated inhibition of ethanol oxidation in hepatocytes. 763 64

Peyronie's disease is a localised, fibrosing condition of the penis that occurs in up to 9% of men. Although its aetiology has not been elucidated, Peyronie's disease probably results from the presence of a predisposing genetic susceptibility combined with an inciting event, most probably trauma. Following appropriate clinical evaluation, initial treatment consists of a trial of oral and/or intralesional pharmacotherapy. Oral therapies most commonly employed include para-aminobenzoate (Potaba) and tocopherol (vitamin E), with colchicine, tamoxifen, propoleum and acetyl-L-carnitine being used less frequently. Placebo-controlled studies examining these agents have failed to show a consistent beneficial effect on Peyronie's disease, with the exception of para-aminobenzoate, which may decrease plaque size and curvature, and acetyl-L-carnitine, which may reduce erectile pain and inhibit disease progression. Intralesional injection therapy for Peyronie's disease is commonly used as a first-line therapy along with oral medications. The current standard of care involves injection with interferon-alpha-2a or -2b, verapamil or collagenase over 2-week intervals for a period of 5-6 months. Interferon-alpha-2b, in particular, has been documented in a large, multicentre, placebo-controlled study to be significantly more effective than placebo in decreasing penile curvature, plaque size, penile pain and plaque density. However, interferon treatment is also associated with significant adverse effects, including fever and other flu-like symptoms. Other available therapies that have not consistently shown efficacy in placebo-controlled studies include corticosteroids and orgotein. Surgery is considered in patients with Peyronie's disease who have not responded to a trial of conservative medical therapy for 1 year and who are precluded from sexual intercourse. Procedures commonly performed include the Nesbit procedure (or variations of the Nesbit), penile plaque incision/excision with or without grafting, and implantation of a penile prosthesis. Further basic scientific research in Peyronie's disease is likely to identify additional targets for future pharmacotherapy.
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PMID:Pharmacological Management of Peyronie's Disease. 1735 13

Peyronie's disease (PD) is a wound-healing disorder in which a fibrotic plaque forms in the tunica albuginea layer of the penis. It clinically presents as any combination of penile pain, angulation, and erectile dysfunction. Recent studies indicate that PD has a prevalence of 3%-9% in adult men. Although the exact etiology has not been established, PD likely results from a predisposing genetic susceptibility combined with an inciting event such as microtrauma during intercourse. During the initial acute phase (6-18 months), the condition may progress, stabilize, or regress. For this reason authorities recommend a more conservative treatment approach, with a trial of oral and/or intralesional pharmacotherapy, before surgical reconstruction is considered. Oral therapies most commonly employed include tocopherol (vitamin E) and paraaminobenzoate (Potaba), with colchicine, tamoxifen, propoleum, and acetyl-L-carnitine being used less often. There are a limited number of long-term placebo-controlled studies with these oral agents, and for the most part, studies have failed to show a consistent beneficial effect. Intralesional injection therapy for PD is more commonly used as a first-line therapy. The current standard of care includes injection with interferon-alpha-2b, verapamil, or collagenase. Interferon-alpha-2b, in particular, has been documented in a large, multicenter, placebo-controlled study to show significant benefit over placebo in decreasing penile curvature, plaque size, penile pain, and plaque density. However, intralesional interferon is associated with posttreatment flu-like symptoms unless patients are premedicated with a nonsteroid anti-inflammatory agent. Other available therapies that have not consistently shown efficacy in placebo-controlled studies include corticosteroids, orgotein, radiation, and extracorporeal shockwave therapy. Surgery is considered when men with PD do not respond to conservative or medical therapy for approximately 1 year and cannot perform satisfactory sexual intercourse. Ongoing basic research in PD will likely identify future targets for medical exploitation.
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PMID:Medical management of Peyronie's disease. 1897 22

Statins are widely used as anti hyperlipidemic agents. Hepatotoxicity is one of their adverse effects appearing in some patients. No protective agents have yet been developed to treat statins-induced hepatotoxicity. Different investigations have suggested L-carnitine as a hepatoprotective agent against drugs-induced toxicity. This study was designed to evaluate the effect of L-carnitine on the cytotoxic effects of statins on the freshly-isolated rat hepatocytes. Hepatocytes were isolated from male Sprague-Dawley rats by collagenase enzyme perfusion via portal vein. Cells were treated with the different concentrations of statins (simvastatin, lovastatin and atorvastatin), alone or in combination with L-carnitine. Cell death, reactive oxygen species (ROS) formation, lipid peroxidation, and mitochondrial depolarization were assessed as toxicity markers. Furthermore, the effects of statins on cellular reduced and oxidized glutathione reservoirs were evaluated. In accordance with previous studies, an elevation in ROS formation, cellular oxidized glutathione and lipid peroxidation were observed after statins administration. Moreover, a decrease in cellular reduced glutathione level and cellular mitochondrial membrane potential collapse occurred. L-carnitine co-administration decreased the intensity of aforementioned toxicity markers produced by statins treatment. This study suggests the protective role of L-carnitine against statins-induced cellular damage probably through its anti oxidative and reactive radical scavenging properties as well as its effects on sub cellular components such as mitochondria. The mechanism of L-carnitine protection may be related to its capacity to facilitate fatty acid entry into mitochondria; possibly adenosine tri-phosphate or the reducing equivalents are increased, and the toxic effects of statins toward mitochondria are encountered.
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PMID:Mitigation of statins-induced cytotoxicity and mitochondrial dysfunction by L-carnitine in freshly-isolated rat hepatocytes. 2648 91