Acute Myoglobinuria Research Articles

Identification of a soluble phosphatidate phosphohydrolase in the developing cotyledons of <i>Momordica</i> <i>charantia</i>

Phosphatidate phosphatase (EC 3.1.3.4), PAP, catalyzes the dephosphorylation of phosphatidate (PtdOH) to form diacylglycerol. In eukaryotes, PAP driven reaction is the committed step in the synthesis of triacylglycerol. A Mg2+ independent PAP activity was identified in the soluble extract of Momordica charantia cotyledons undergoing maturation. While the microsomal fraction of the extract gave only 10% of the PAP activity, the remaining 90% of the activity was associated with the soluble fraction. At pH 3.0, the soluble PAP was bound to S column and eluted with glycine-HCl buffer containing high salt. The pH and temperature optima of the PAP activity were 6.0 and 53℃, respectively. Under optimum assay condition, the Vmax and Km for dioleoyl phosphatidic acid were 1.89 ηkat/mg of protein and 142 μM, respectively. For the synthetic substrate, ρ-nitrophenylphosphate, ρ- NPP, the Vmax and Km were 10.4 ηkat/mg of protein and 107 μM, respectively. The inclusion of Mg2+ and β-mercaptoethanol into the reaction mix did not change the enzyme activity nor did the addition of N-ethylmaleimide and phenylglyoxal, which indicates that cysteine and arginine are not involved in catalysis of PtdOH. The addition of Mg2+ up to 10 mM also did not change the level of PAP activity. Triton X-100, however, inhibited the activity. This is the first documented case of an in vitro PAP activity in the developing cotyledons of Momordica charantia. The PAP described here could serve as a model for lipin-1 or lipin-2 in humans. Mutations in these genes lead to acute myoglobinuria in human infants.

Fluorescence spectroscopy measures yeast PAH1-encoded phosphatidate phosphatase interaction with liposome membranes

Phosphatidate (PA) phosphatase, the enzyme that catalyzes the penultimate step in triacylglycerol synthesis, is a cytosolic enzyme that must associate with the membrane where its substrate PA resides. Fluorescence spectroscopy was used to measure the interaction of yeast PAH1-encoded PA phosphatase with model liposome membranes. PA phosphatase contains five tryptophan residues and exhibited inherit fluorescence that increased upon interaction with phosphatidylcholine liposomes. The interaction was enhanced by inclusion of other phospholipids and especially the substrate PA. Interaction was dependent on both the concentration of phosphatidylcholine-PA liposomes as well as the surface concentration of PA in liposomes. Mg(2+) ions, which were required for catalysis, did not affect PA phosphatase interaction with phosphatidylcholine-PA liposomes. PA phosphatase was a substrate for protein kinase A, protein kinase C, and casein kinase II, and these phosphorylations decreased PA phosphatase interaction with phosphatidylcholine-PA liposome membranes.

The lipin family: mutations and metabolism

The family of three lipin proteins act as phosphatidate phosphatase (PAP) enzymes required for glycerolipid biosynthesis, and also as transcriptional coactivators that regulate expression of lipid metabolism genes. The genes for lipin-1, lipin-2 and lipin-3 are expressed in key metabolic tissues, including adipose tissue, skeletal muscle and liver, but the physiological functions of each member of the family have not been fully elucidated. Here we examine the most recent studies that provide information about the roles of lipin proteins in metabolism and human disease. Recent studies have identified mutations that cause lipin-1 or lipin-2 deficiency in humans, leading to acute myoglobinuria in childhood or the inflammatory disorder Majeed syndrome, respectively. The effects of lipin-1 deficiency appear to include both the loss of glycerolipid building blocks and the accumulation of lipid intermediates that disrupt cellular function. Several studies have demonstrated that polymorphisms in the LPIN1 and LPIN2 genes are associated with metabolic disease traits, including insulin sensitivity, diabetes, blood pressure and response to thiazolidinedione drugs. Furthermore, lipin-1 expression levels in adipose tissue and/or liver are positively correlated with insulin sensitivity. Studies of lipin-1 in adipocytes have shed some light on its relationship with insulin sensitivity. Lipin-1 and lipin-2 are required for normal lipid homeostasis and have unique physiological roles. Future studies, for example using engineered mouse models, will be required to fully elucidate their specific roles in normal physiology and disease.

LeaPIN’ toward the cause of myoglobinuria in childhood

Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood Zeharia et al. (2008) The American Journal of Human Genetics 83: 1–6

Mutations in LPIN1 Cause Recurrent Acute Myoglobinuria in Childhood

Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using homozygosity mapping, we identified six deleterious mutations in the LPIN1 gene in patients who presented at 2-7 years of age with recurrent, massive rhabdomyolysis. The LPIN1 gene encodes the muscle-specific phosphatidic acid phosphatase, a key enzyme in triglyceride and membrane phospholipid biosynthesis. Of six individuals who developed statin-induced myopathy, one was a carrier for Glu769Gly, a pathogenic mutation in the LPIN1 gene. Analysis of phospholipid content disclosed accumulation of phosphatidic acid and lysophospholipids in muscle tissue of the more severe genotype. Mutations in the LPIN1 gene cause recurrent rhabdomyolysis in childhood, and a carrier state may predispose for statin-induced myopathy.

Thrombotic Microangiopathy and Renal Failure Exacerbated by ε-Aminocaproic Acid

w c v t i e s -Aminocaproic acid (EACA) is used to treat bleeding associated with systemic brinolysis, as well as hematuria resulting rom urinary tract procedures or tumors. EACA nhibits urokinase and other activators of plasinogen, decreasing the formation of plasmin nd inhibiting the breakdown of fibrin. ACA-associated renal failure may be caused y obstruction of the upper urinary system by lood clots, hypotension with acute tubular ecrosis, renal infarction, and myoglobinuria. his is the first report of EACA causing renal ailure by accelerating a preexisting thromotic microangiopathic process.

Cytochrome c oxidase deficiency presenting as recurrent neonatal myoglobinuria

Markedly reduced cytochrome c oxidase (COX) activity was found in cultured skin fibroblasts of an infant with recurrent episodes of acute myoglobinuria, hypertonia, muscle stiffness and elevated plasma levels of sarcoplasmic enzymes (creatine kinase 96950 U/1, normal below 150) since the age of 3 weeks (COX activity: 36 nmol/min/mg protein; normal 65–440; COX/succinate cytochrome c reductase ratio: 1.4, normal 3.0 ± 0.4). The expression of the disease in cultured fibroblasts allowed us to carry out a prenatal diagnosis during the next pregnancy.Hitherto, mitochondrial respiratory chain deficiency has not been established as a cause of recurrent myoglobinuria in childhood. Since most cases of myoglobinurias remain poorly understood, we suggest giving consideration to respiratory chain deficiency in elucidating the origin of unexplained recurrent myoglobinuria in childhood, especially when seemingly unrelated symptoms are present.

Rhabdomyolysis following life‐threatening acute asthma attack

The authors report a life-threatening, acute asthmatic attack in a young man, which was followed by rhabdomyolysis and acute myoglobinuria. A discussion of the possible rôle of the pharmacological treatment of asthma in initiating muscle damage is included, based on a review of the current literature.

Muscle Carnitine Contents in Severely Handicapped Children with Acute Myoglobinuria

Muscle Carnitine Contents in Severely Handicapped Children with Acute Myoglobinuria

Acute Myoglobinuria as a Fatal Complication of Heroin Addiction

A fatal case of myoglobinuria complicating heroin addiction is described. Clinically the patient had no overt symptoms of rhabdomyolysis. Pathologists should be alerted to this rare complication in heroin addicts who die of no apparent cause. The antimyoglobin immunoperoxidase technique is useful in confirming the diagnosis.

Acute Tubular Necrosis After Inhalation Exposure to Methylene Chloride. Report of a Case

• Nephrotoxic reaction occurred after inhalation exposure to methylene chloride. This exposure is associated with acute renal failure, myoglobinuria, hypocomplementemia, and liver enzyme elevations. Pathologic specimens, both light and electron microscopic, demonstrate renal tubular damage. We conclude that methylene chloride may have potential as both a hepatotoxic and nephrotoxic agent when inhaled at high concentrations over an extended period of time. ( Arch Intern Med 1985;145:145-146)

Acute myoglobinuria and heroin snorting

ACUTE rhabdomyolysis with myoglobinuria has been associated with hereditary enzyme deficiencies, severe exertion, metabolic derangements, trauma, and toxins, most notably alcohol. In recent years, intravenous heroin injection has been reported increasingly as a cause of acute rhabdomyolysis. This report details a case of myoglobinuria associated with inhalation of a heroin mixture as snuff. <h3>Report of a Case</h3> A 20-year-old man was hospitalized because of muscle pain of four days' duration. He was in good health until five days previously, when he noted tea-colored urine. The following day he experienced cramping pain in both thighs that was aggravated by movement. Attempts to relieve the pain by exercising increased the discomfort. Over the next several days, the pain worsened and spread to involve the calves and upper arms. He denied recent trauma or strenuous exercise. He admitted occasional use of alcohol and marijuana but denied the use of any other drugs. He

Acute Myoglobinuria and Heroin Snorting

ACUTE rhabdomyolysis with myoglobinuria has been associated with hereditary enzyme deficiencies, severe exertion, metabolic derangements, trauma, and toxins, most notably alcohol. In recent years, intravenous heroin injection has been reported increasingly as a cause of acute rhabdomyolysis. This report details a case of myoglobinuria associated with inhalation of a heroin mixture as snuff. Report of a Case A 20-year-old man was hospitalized because of muscle pain of four days' duration. He was in good health until five days previously, when he noted tea-colored urine. The following day he experienced cramping pain in both thighs that was aggravated by movement. Attempts to relieve the pain by exercising increased the discomfort. Over the next several days, the pain worsened and spread to involve the calves and upper arms. He denied recent trauma or strenuous exercise. He admitted occasional use of alcohol and marijuana but denied the use of any other drugs. He

Influenza a viral infection associated with acute renal failure

The clinical and laboratory findings in four cases of acute renal failure following the onset of influenza A viral Infection (Port Chalmers/1/73) are presented. Although the pathophysiologic mechanisms affecting the kidney in these cases varied, the ensuing renal failure in each patient was severe. Findings suggestive of acute myoglobinuria developed in one patient, and disseminated intravascular coagulation (DIC) occurred in another. The role of viruses in the pathogenesis of renal disease is reviewed. Despite inconclusive evidence that the influenza virus can cause human renal disease, the secondary pathways that can be triggered by viral infections may be even more significant in producing various degrees of renal dysfunction. The occurrence of renal failure during an episode of influenza represents a serious complication which may influence significantly the morbidity and mortality of patients with this viral infection.

Acute Myoglobinuria in an Infant with Picorna-virus like Crystals; A Case Report

Acute Myoglobinuria in an Infant with Picorna-virus like Crystals; A Case Report

Myoglobinuria Precipitated by Viral Infection

A 30-year-old man had an episode of acute myoglobinuria in association with infection due to type A2 (Hong Kong) influenza virus in December 1968. He was well until he again experienced myoglobinuria in July 1972. This episode was in association with a coxsackievirus B5 infection. The occurrence of two separate instances of myoglobinuria with demonstrated virus infections is interpreted as clear evidence that virus infections can precipitate rhabdomyolysis.

Exercise myoglobinuria.

Letters, Comments, and Corrections1 November 1972Exercise MyoglobinuriaM. C. KOSHY, M.D., DONALD SILVERMAN, M.D., JAMES M. GRANT, M.D.M. C. KOSHY, M.D.Search for more papers by this author, DONALD SILVERMAN, M.D.Search for more papers by this author, JAMES M. GRANT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-77-5-817_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: A case of exercise-induced myoglobinuria reported by Robert W. Hamilton and associates (77:77-82, 1972) prompts us to report a similar case of our own.A 25-year-old white man was admitted to St. Vincent's Hospital, Bridgeport, with rhabdomyolysis. He rapidly developed respiratory paralysis and acute renal failure. There were no apparent precipitating causes except a probable attack of viral respiratory infection (1). However, a year ago he was treated here for rhabdomyolysis after muscular exercise in a football game, but without renal tubular necrosis or other complications.The laboratory data included persistent hyperkalemia, which required K+ free peritoneal...Reference1. SIMONROVNERBERLIN NRB: Acute myoglobinuria associated with type A2 (Hong Kong) influenza. JAMA 212: 1704-1705, 1970 CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: M. C. KOSHY, M.D.; DONALD SILVERMAN, M.D.; JAMES M. GRANT, M.D.Affiliations: Bridgeport Hospital 267 Grant Street Bridgeport, Conn. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byRhabdomyolysis And Myoglobinuria in ChildhoodExercise Myoglobinuria 1 November 1972Volume 77, Issue 5Page: 817-818KeywordsAcute renal failureExerciseGamesNecrosisParalysisResearch laboratoriesRhabdomyolysisUpper respiratory tract infections ePublished: 1 December 2008 Issue Published: 1 November 1972 PDF downloadLoading ...

Acute myoglobinuria with or without drug usage

<h3>To the Editor.—</h3> The report of Richter et al on myoglobinuria associated with heroin addiction (<b>216</b>:1172 1971) described four patients with a syndrome involving skeletal muscles which was both clinically and pathologically distinctive. In each instance, onset of illness followed heroin use. Two of the four developed renal failure, presumably related to myoglobinuria. In one, death followed ten days of coma. With these exceptions, dysfunction of other organ systems was not striking, nor were there notable alterations in blood chemistry values (excluding, of course, elevation of enzyme levels reflecting muscle necrosis). Since May 1970, I have personally seen 17 patients with rhabdomyolysis and myoglobinuria,¹15 at the Queens Hospital Center, two at the Long Island Jewish Medical Center. The diffuse inflammation of muscle described by Richter was the same, and the microscopic abnormalities in my patients were identical to those illustrated in their article. In no case could

Acute Myoglobinuria Associated With Heroin Addiction

Acute rhabdomyolysis was observed as a new complication of intravenous heroin-adulterant injections in four men. Clinical features included generalized muscle tenderness, edema, and profound weakness. Myoglobinuria was detected by a specific immunological method which measured levels up to 3.25 mg/ml. Serum myoglobin levels as high as 0.310 mg/ml were found, with serum creatine phosphokinase levels up to 14,000 units. Needle electromyography showed myopathic motor unit potentials in all muscles tested, most marked proximally. Histologic examination demonstrated acute myolysis, and in one case an unusual picture consistent with tubular aggregates. Renal failure occurred in two patients, one of whom survived. Resolution of weakness varied from two to six weeks. The process recurred in one patient following a subsequent heroin injection.

Acute myoglobinuria associated with heroin addiction

Acute myoglobinuria associated with heroin addiction