Reduction of pantethine in rabbit ocular lens homogenate

Fisher, Daniel H.; Szulc, Michael

doi:10.1016/s0731-7085(96)01878-x

Cited by 4 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…How, exactly, pantethine can be converted into CoA is currently unclear. Classic biochemical studies using cell extracts showed that pantethine can be reduced into pantetheine (25,26) and that this can be converted into 4′-phosphopantetheine (14). The latter is an intermediate of the canonical de novo biosynthesis pathway and thus here, upstream from PPAT, the CoA de novo synthesis pathways starting from vitB5 and from pantethine may converge (Fig.…”

Section: Discussionmentioning

confidence: 99%

Pantethine rescues a Drosophila model for pantothenate kinase–associated neurodegeneration

Rana

Seinen

Siudeja

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

142

165

View full text Add to dashboard Cite

Pantothenate kinase-associated neurodegeneration (PKAN), a progressive neurodegenerative disorder, is associated with impairment of pantothenate kinase function. Pantothenate kinase is the first enzyme required for de novo synthesis of CoA, an essential metabolic cofactor. The pathophysiology of PKAN is not understood, and there is no cure to halt or reverse the symptoms of this devastating disease. Recently, we and others presented a PKAN Drosophila model, and we demonstrated that impaired function of pantothenate kinase induces a neurodegenerative phenotype and a reduced lifespan. We have explored this Drosophila model further and have demonstrated that impairment of pantothenate kinase is associated with decreased levels of CoA, mitochondrial dysfunction, and increased protein oxidation. Furthermore, we searched for compounds that can rescue pertinent phenotypes of the Drosophila PKAN model and identified pantethine. Pantethine feeding restores CoA levels, improves mitochondrial function, rescues brain degeneration, enhances locomotor abilities, and increases lifespan. We show evidence for the presence of a de novo CoA biosynthesis pathway in which pantethine is used as a precursor compound. Importantly, this pathway is effective in the presence of disrupted pantothenate kinase function. Our data suggest that pantethine may serve as a starting point to develop a possible treatment for PKAN.coenzyme A | mitochondria | PKAN | oxidative stress | lifespan

show abstract

Section: Discussionmentioning

confidence: 99%

Pantethine rescues a Drosophila model for pantothenate kinase–associated neurodegeneration

Rana

Seinen

Siudeja

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

142

165

View full text Add to dashboard Cite

show abstract

“…It was reported that both pantothenate and pantethine could lead to the formation of coenzyme A via metabolic pathways in vertebrates (Ranganathan et al, 1982;Fisher & Szulc, 1997) and parasites such as Plasmodium falciparum (Saliba et al, 1998). These organisms synthesise coenzyme A from pantothenate and utilise it for their energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…As in the case of pantethine, this vitamin consists of two molecules of pantetheine (Fisher & Szulc, 1997), which is subsequently converted to coenzyme A. If the above biochemical processes could occur in the nematodes, then C. elegans could utilise pantethine alone for the synthesis of coenzyme A.…”

Section: Discussionmentioning

confidence: 99%

“…Caenorhabditis elegans was cultivated in the stock medium HS-YE-HLE, which consists of 4% Hi-Soy (from Shils and Young (1988) and Fisher and Szulc (1997)). …”

Section: Stock Medium and Culturementioning

confidence: 99%

“…Pantothenate serves as a metabolic precursor to the synthesis of coenzyme A and acyl carrier protein (ACP) (Fisher & Szulc, 1997;Saliba et al, 1998;Ottenhof et al, 2004;Zhang et al, 2004). Pantethine consists of two molecules of pantothenate, which are connected by a disulphide bond.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Nutritional requirements for pantothenate, pantethine or coenzyme A in the free-living nematode Caenorhabditis elegans

Balachandar¹,

Lu²

2005

Nematol

View full text Add to dashboard Cite

Caenorhabditis elegans is a free-living nematode cultured in an axenic medium, the Caenorhabditis elegans Maintenance Medium (CeMM), which contains B-vitamins, salts, amino acids, nucleic acid substituents, growth factors and glucose as an energy source. After initial experiments established that either pantothenate or pantethine would satisfy the vitamin B5 requirement in C. elegans, reproduction in the nematodes was measured in eight equimolar concentrations of calcium pantothenate, pantethine or coenzyme A. The optimal levels for pantothenate were found to be 7.5, 30 and 120 µg ml −1 . The optimal levels for pantethine and coenzyme A were found to be 35 µg ml −1 and 100 µg ml −1 , respectively. Among the three compounds, coenzyme A (at 100 µg/ml) supported a significantly greater population growth and, perhaps, is a more metabolically active form. Mild toxicity was demonstrated for pantothenate at 480 µg ml −1 , pantethine at 560 and 140 µg ml −1 , and coenzyme A was found to exhibit toxicity at 410 and 1700 µg ml −1 . Based on our results, we recommend that in the future the CeMM could be supplemented with pantothenate (7.5 µg ml −1 ) alone.

show abstract

Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease

Zizioli

Tiso

Guglielmi

et al. 2016

Neurobiology of Disease

View full text Add to dashboard Cite

Pantothenate Kinase Associated Neurodegeneration (PKAN) is an autosomal recessive disorder with mutations in the pantothenate kinase 2 gene (PANK2), encoding an essential enzyme for Coenzyme A (CoA) biosynthesis. The molecular connection between defects in this enzyme and the neurodegenerative phenotype observed in PKAN patients is still poorly understood. We exploited the zebrafish model to study the role played by the pank2 gene during embryonic development and get new insight into PKAN pathogenesis. The zebrafish orthologue of hPANK2 lies on chromosome 13, is a maternal gene expressed in all development stages and, in adult animals, is highly abundant in CNS, dorsal aorta and caudal vein. The injection of a splice-inhibiting morpholino induced a clear phenotype with perturbed brain morphology and hydrocephalus; edema was present in the heart region and caudal plexus, where hemorrhages with reduction of blood circulation velocity were detected. We characterized the CNS phenotype by studying the expression pattern of wnt1 and neurog1 neural markers and by use of the Tg(neurod:EGFP/sox10:dsRed) transgenic line. The results evidenced that downregulation of pank2 severely impairs neuronal development, particularly in the anterior part of CNS (telencephalon). Whole-mount in situ hybridization analysis of the endothelial markers cadherin-5 and fli1a, and use of Tg(fli1a:EGFP/gata1a:dsRed) transgenic line, confirmed the essential role of pank2 in the formation of the vascular system. The specificity of the morpholino-induced phenotype was proved by the restoration of a normal development in a high percentage of embryos co-injected with pank2 mRNA. Also, addition of pantethine or CoA, but not of vitamin B5, to pank2 morpholino-injected embryos rescued the phenotype with high efficiency. The zebrafish model indicates the relevance of pank2 activity and CoA homeostasis for normal neuronal development and functioning and provides evidence of an unsuspected role for this enzyme and its product in vascular development.

show abstract

Reduction of pantethine in rabbit ocular lens homogenate

Cited by 4 publications

References 14 publications

Pantethine rescues a Drosophila model for pantothenate kinase–associated neurodegeneration

Pantethine rescues a Drosophila model for pantothenate kinase–associated neurodegeneration

Nutritional requirements for pantothenate, pantethine or coenzyme A in the free-living nematode Caenorhabditis elegans

Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease

Contact Info

Product

Resources

About