Pantethine

Not to be confused with pantetheine.
Pantethine
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
ATC code A11HA32
16816-67-4 Yes
ChEMBL ChEMBL2104786
ChemSpider 4515 Yes
Jmol-3D images Image
PubChem 4677
UNII 7K81IL792L Yes
Properties
C22H42N4O8S2
Molar mass 554.723 g/mol
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
1
2
0
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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Infobox references

Pantethine (bis-pantethine or co-enzyme pantethine) is a dimeric form of pantothenic acid (vitamin B5). It is composed of two molecules of pantothenic acid linked by cysteamine bridging groups. The monomer of this compound is known as pantetheine and is an intermediate in the production of Coenzyme A by the body. Pantethine is considered the more biologically active form of vitamin B5, but it is less stable, decomposing over time if it is not kept refrigerated. Most vitamin B5 supplements are therefore in the form of calcium pantothenate, a salt of pantothenic acid.

Dietary supplementation

Pantethine is available as a dietary supplement because of evidence of its health benefits, and is used to treat acne and improve the blood-cholesterol profile. It is marketed as the main ingredient in OTC supplements for the treatment of acne, and is reportedly used to treat gout and chronic fatigue syndrome. There is no upper tolerable intake, according to the FDA.

In multiple clinical trials of patients with elevated cholesterol and triglycerides, total and LDL cholesterol were decreased by 12%, triglycerides decreased by 18%, and HDL cholesterol was increased by 9%.[1][2] 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 tested 300 mg/day with more modest but still statistically significant results.[3]

Further carefully controlled trials of 600 and 900 mg/d doses have shown statistically significant lowering of LDL cholesterol in individuals with greatly or moderately elevated levels of blood lipids.[4]

Physiological effects

Although pantethine can serve as a precursor for generation of vitamin B5, this is not thought to be the mechanism of action. Vitamin B5 requirements are on the order of 5 mg/day.

Two mechanisms of action are proposed for pantethine.[5] In the first, pantethine serves as the precursor for synthesis of coenzyme A. In the second, 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.

References

  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. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.