Pantethine

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Not to be confused with pantetheine.
Pantethine
Pantethine structure.png
Names
IUPAC name
N-[2-[2-[2-[3-(2,4-Dihydroxy-3,3-dimethyl-butanoyl)aminopropanoylamino ]ethyldisulfanyl]ethylcarbamoyl]ethyl]-2,4-dihydroxy-3,3-dimethyl-butanamide
Other names
Bis-pantethine
Co-enzyme pantethine
Identifiers
16816-67-4 YesY
ChEMBL ChEMBL2104786 N
ChemSpider 4515 YesY
Jmol 3D model Interactive image
PubChem 4677
UNII 7K81IL792L YesY
Properties
C22H42N4O8S2
Molar mass 554.723 g/mol
Pharmacology
A11HA32 (WHO)
Hazards
NFPA 704
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oil Health code 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g., chloroform Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no codeNFPA 704 four-colored diamond
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Pantethine (bis-pantethine or co-enzyme pantethine) is a dimeric form of pantetheine, which is produced from pantothenic acid (vitamin B5) by the addition of cysteamine. Pantethine is composed of two molecules of pantetheine linked by a bridging disulfide. Pantetheine is an intermediate in the production of Coenzyme A by the body. Most vitamin B5 supplements are in the form of calcium pantothenate, a salt of pantothenic acid, with doses in the range of 5 to 10 mg/day. In contrast, pantethine is sold as a dietary supplement for lowering blood cholesterol and triglycerides at doses of 500 to 1200 mg/day

Dietary supplementation[edit]

Pantethine is available in the United States as a dietary supplement because of evidence of its health benefits for lowering elevated LDL-cholesterol and triglycerides, and raising HDL-cholesterol (the 'good' cholesterol). In multiple clinical trials of patients with elevated cholesterol and triglycerides, total and LDL cholesterol were decreased by an average of 12%, triglycerides decreased by 19%, and HDL cholesterol was increased by 9%.[1][2][3] These clinical trials were conducted with daily intakes ranging from 600 to 1200 mg/day. Within this dose range there is no evidence of a dose-effect relationship, i.e. changes in lipid concentrations overlapped across the range of doses. Direct dose-response evidence is not available because no trial tested more than one dose. A few trials conducted in Japan tested 300 mg/day and reported decreases in total cholesterol of about 4%, increases in HDL-cholesterol of 5% and inconsistent results for triglycerides.[4] Most of the literature on pantethine and lipids is 20–30 years old, but recent carefully controlled trials of 600 and 900 mg/d doses have shown similar statistically significant lowering of LDL cholesterol in individuals with greatly or moderately elevated levels of blood lipids.[5][6]

Physiological effects[edit]

Although pantethine can serve as a precursor for generation of vitamin B5 and consumption of therapeutic amounts of pantethine results in higher circulating concentrations of vitamin B5, this is not thought to be the mechanism of action. Vitamin B5 requirements are on the order of 5 mg/day. High doses of vitamin B5 do not result in the lipid changes seen with pantethine.

Two mechanisms of action are proposed for pantethine.[7] In the first, pantethine serves as the precursor for synthesis of coenzyme A. CoA is involved in the transfer of acetyl groups, in some instances to attach to proteins closely associated with activating and deactivating genes. By this theory, either the genes responsible for cholesterol and triglyceride synthesis are suppressed or the genes governing the catabolism of compounds are turned on. In the second theory, pantethine is converted to two pantetheine molecules which are in turn metabolized to form two pantethenic acid and two cysteamine molecules. Cysteamine is theorized to bind to and thus inactivate sulfur-containing amino acids in liver enzymes involved in the production of cholesterol and triglycerides. What is known is that high doses of the related vitamin - pantothenic acid - has no effect on lipids.

References[edit]

  1. ^ Binaghi, P; Cellina, G; Lo Cicero, G; Bruschi, F; Porcaro, E; Penotti, M (1990). "Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age". Minerva medica 81 (6): 475–9. PMID 2359503. 
  2. ^ Arsenio, L; Bodria, P; Magnati, G; Strata, A; Trovato, R (1986). "Effectiveness of long-term treatment with pantethine in patients with dyslipidemia". Clinical therapeutics 8 (5): 537–45. PMID 3094958. 
  3. ^ Chen, Ya-qin; Zhao, Shui-ping; Zhao, Yu-hong (2015). "Efficacy and tolerability of coenzyme A vs pantethine for the treatment of patients with hyperlipidemia: A randomized, double-blind, multicenter study". Journal of Clinical Lipidology 9 (5): 692–697. doi:10.1016/j.jacl.2015.07.003. ISSN 1933-2874. 
  4. ^ Gaddi, A; Descovich, GC; Noseda, G; Fragiacomo, C; Colombo, L; Craveri, A; Montanari, G; Sirtori, CR (1984). "Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipoproteinemia". Atherosclerosis 50 (1): 73–83. doi:10.1016/0021-9150(84)90009-1. PMID 6365107. 
  5. ^ Rumberger, JA; Napolitano, J; Azumano, I; Kamiya, T; Evans, M (2011). "Pantethine, a derivative of vitamin B(5) used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled investigation". Nutr Res 31 (8): 608–15. doi:10.1016/j.nutres.2011.08.001. PMID 21925346. 
  6. ^ Evans M, Rumberger JA, Azumano I, Napolitano JJ, Citrolo D, Kamiya T (2014). "Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation". Vasc Health Risk Manag 10: 89–100. doi:10.2147/VHRM.S57116. PMC 3942300. PMID 24600231. 
  7. ^ McCarty MF (2001). "Inhibition of acetyl-CoA carboxylase by cystamine may mediate the hypotriglyceridemic activity of pantethine". Medical Hypotheses 56 (3): 314–317. doi:10.1054/mehy.2000.1155.