Muscle Carnitine Palmityltransferase Deficiency and Myoglobinuria

DiMauro, Salvatore; DiMauro, Paola M. Melis

doi:10.1126/science.182.4115.929

Cited by 441 publications

(120 citation statements)

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“…Creatine kinase myocardial band (CK-MB) is also increased. 2 Carnitine palmitoyltransferase deficiency was first described in 1973 by Di Mauro et al 3 It results in a defect of mitochondrial fatty acid oxidation which does not manifest until the patient is fasting and fatty acid oxidation begins to play a role in energy production. Fatty acids are activated to form CoA thioesters through acyl-CoA synthetases.…”

Section: Discussionmentioning

confidence: 99%

Anesthetic management of a parturient with carnitine palmitoyltransferase ii deficiency

Lilker

Kasodekar

Goldszmidt

2006

Can J Anesth/J Can Anesth

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Purpose: To report the anesthetic management of a patient with carnitine palmitoyltransferase II deficiency who presented for labour and delivery. Clinical features:A 30-yr-old primiparous woman with known carnitine palmitoyltransferase II deficiency and a past history of exercise induced muscle pain, weakness and myoglobinuria presented in active labour. Management consisted of an early epidural for labour and continuous dextrose infusion with frequent blood sugar monitoring. She had an uneventful spontaneous vaginal delivery. She experienced a single asymptomatic episode of hypoglycemia on the first postpartum day. Her serum creatine kinase was six times normal at 24 hr postdelivery and remained elevated for three days without evidence of rhabdomyolysis. The remainder of her postpartum course was uneventful. Conclusion:Labour and delivery is a potential precipitant of rhabdomyolysis in patients with carnitine palmitoyltransferase II deficiency. The normal postpartum creatine kinase elevation (two to four times baseline at 24 hr) must be taken into account when monitoring these patients. On the basis of the physiologic principles, institution of early epidural analgesia to blunt the stress response to labour and delivery, continuous dextrose infusion and frequent glucose monitoring during labour and postpartum are the mainstays of management. Objectif

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Section: Discussionmentioning

confidence: 99%

Anesthetic management of a parturient with carnitine palmitoyltransferase ii deficiency

Lilker

Kasodekar

Goldszmidt

2006

Can J Anesth/J Can Anesth

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“…The first recognized case of human FAO disease was described in 1973 as a CPT2 deficiency in muscle cells [102]. Since then, mutations in at least 19 transport proteins and enzymes involved in FAO have been identified (Table 2).…”

Section: Fao Diseasementioning

confidence: 99%

Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease

2016

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SynopsisMitochondria provide the main source of energy to eukaryotic cells, oxidizing fats and sugars to generate ATP . Mitochondrial fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are two metabolic pathways which are central to this process. Defects in these pathways can result in diseases of the brain, skeletal muscle, heart and liver, affecting approximately 1 in 5000 live births. There are no effective therapies for these disorders, with quality of life severely reduced for most patients. The pathology underlying many aspects of these diseases is not well understood; for example, it is not clear why some patients with primary FAO deficiencies exhibit secondary OXPHOS defects. However, recent findings suggest that physical interactions exist between FAO and OXPHOS proteins, and that these interactions are critical for both FAO and OXPHOS function. Here, we review our current understanding of the interactions between FAO and OXPHOS proteins and how defects in these two metabolic pathways contribute to mitochondrial disease pathogenesis.Key words: disease, mitochondria, protein complex assembly, protein interactions, supercomplex. MITOCHONDRIAL METABOLISMMitochondria occupy almost all human cell types and are involved in essential metabolic and cellular processes, including calcium and iron homoeostasis, apoptosis, innate immunity and haeme biosynthesis [1]. However, the primary function of mitochondria is the production of energy in the form of ATP [2][3][4]. ATP is the body's energy currency, playing vital roles in cell differentiation, growth and reproduction, thermogenesis and powering the contraction of muscles for movement [1]. In humans, ATP is produced by two different processes; through the breakdown of glucose or other sugars in Abbreviations: ACAD9, acyl-CoA dehydrogenase 9; BN-PAGE, blue native polyacrylamide gel electrophoresis; CACT, carnitine acylcarnitine translocase; CI, oxidative phosphorylation complex I (NADH: ubiquinone oxidoreductase, EC 1.6.5.3); CII, oxidative phosphorylation complex II (succinate: ubiquinone oxidoreductase, EC 1.3.5.1); CIII, oxidative phosphorylation complex III (ubiquinol: ferricytochrome c oxidoreductase, EC 1.10.2.2); CIV, oxidative phosphorylation complex IV (cytochrome c oxidase, EC 1.9.3.1); COPP , complex one phylogenetic profile; CPT1, carnitine O-palmitoyltransferase 1; CPT2, carnitine O-palmitoyltransferase 2; CV, OXPHOS complex V (FoF 1 -ATP synthetase, EC; 3.6.3.14); ECHS1, enoyl-CoA hydratase, short chain 1, mitochondrial; ECI1, enoyl-CoA delta isomerase, 1; ETF, electron transfer flavoprotein; ETFA, electron transfer flavoprotein alpha subunit; ETFB, electron transfer flavoprotein beta subunit; ETF-QO, electron transfer flavoprotein: ubiquinone oxidoreductase; FAD, flavin adenine dinucleotide; FADH 2 , reduced flavin adenine dinucleotide; FAO, fatty acid β-oxidation; H 2 O, water; HADH, hydroxyacyl-CoA dehydrogenase; KAT, 3-ketoacyl-CoA thiolase, mitochondrial; LCAD, long chain acyl-CoA dehydrogenase; LCEH, long chain enoyl-CoA hydra...

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“…However, all of this changed in the mid-1970s following two important developments. First, it became clear that inherited defects at the level of the mitochondrial CPT system form the basis of serious human disease [4]. Second, it was recognized that, at least in liver, CPT I plays a pivotal role in the regulation of fatty acid oxidation [S].…”

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confidence: 99%

The Mitochondrial Carnitine Palmitoyltransferase System — From Concept to Molecular Analysis

McGarry

Brown

1997

European Journal of Biochemistry

1,450

1,220

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First conceptualized as a mechanism for the mitochondrial transport of long-chain fatty acids in the early 1960s, the carnitine palmitoyltransferase (CPT) system has since come to be recognized as a pivotal component of fuel homeostasis. This is by virtue of the unique sensitivity of the outer membrane CPT I to the simple molecule, malonyl-CoA. In addition, both CPT I and the inner membrane enzyme, CPT 11, have proved to be loci of inherited defects, some with disastrous consequences. Early efforts using classical approaches to characterize the CPT proteins in terms of structure/function/regulatory relationships gave rise to confusion and protracted debate. By contrast, recent application of molecular biological tools has brought major enlightenment at an exponential pace. Here we review some key developments of the last 20 years that have led to our current understanding of the physiology of the CPT system, the structure of the CPT isofornis, the chromosomal localization of their respective genes, and the identification of mutations in the human population.

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Muscle Carnitine Palmityltransferase Deficiency and Myoglobinuria

Cited by 441 publications

References 16 publications

Anesthetic management of a parturient with carnitine palmitoyltransferase ii deficiency

Anesthetic management of a parturient with carnitine palmitoyltransferase ii deficiency

Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease

The Mitochondrial Carnitine Palmitoyltransferase System — From Concept to Molecular Analysis

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