The following is an excerpt from the article,
Pantethine: A Review of their Biochemistry and Therapeutic Applications first published in Alternative Medicine Review, Volume 2, Number 5.

The biological functions of pantethine as an enzyme component is dependent on its degradation to pantetheine and its subsequent incorporation into CoA or ACP. Both CoA and ACP function as acyl or acetyl carriers. CoA performs this function by forming thioester linkages between its sulfhydryl group and available acyl or acetyl groups. In this manner, CoA facilitates the transfer of acetyl groups from pyruvate to oxaloacetate in order to initiate the tricarboxylic acid (TCA) cycle. Before pyruvate can be used in the TCA cycle, it must be converted to acetyl-CoA by oxidative carboxylation. Coenzyme-A, as well as thiamine, lipoic acid, riboflavin, niacin, and magnesium are all required.

The TCA cycle and CoA dependent pathways are diagrammed below.



Directly or indirectly, CoA is involved in the breakdown of the carbon skeleton of most amino acids. Alanine, cystine, cysteine, glycine, serine, threonine, and hydroxyproline are metabolized to pyruvate and then enter the TCA cycle with the help of CoA. CoA is directly involved with the breakdown of leucine, lysine, and tryptophan. The degradation of the pyrimidine bases, cytosine, uracil, and thymine, is also dependent on CoA.

Coenzyme-A can direct acetyl groups into the formation of all the polyisoprenoid containing compounds, which include Coenzyme-Q10 (CoQ10), dolichol, squalene, and cholesterol. Dolichol is a sugar carrier used in the synthesis of glycoproteins. In addition to this indirect role in the formation of glycoproteins, CoA is also used in the formation of N-acetylated derivatives of amino sugars, including N-acetylglucosamine, N-acetylgalactosamine, N-acetylmannosamine, and N-acetylneuraminic acid.

Because of the involvement of CoA in the initial steps of cholesterol synthesis, all down-stream metabolites of cholesterol, including steroids, Vitamin D, and bile acids, are indirectly impacted by CoA.

CoA is required for the acetylation of choline to form the neurotransmitter acetylcholine. It is also used for acetylation conjugations of phenol amines, sulfur amino, aliphatic amines, and hydrazines. The biosynthetic pathway of melatonin also requires an acetylation reaction.

Pantetheine has a wide array of functions which interact with fat metabolism, including synthesis, degradation, and transportation of fatty acids. The formation of fatty acids from excess amounts of glycogen involves CoA. In the first step in the synthesis of fatty acids, malonyl-CoA is formed by the carboxylation of acetyl-CoA. Fatty acid chain elongation is also dependent on CoA. The cytoplasmic fatty acid synthesizing system uses ACP, a protein analog of CoA derived from pantetheine to bind intermediates in the synthesis of long-chain fatty acids. CoA is also needed for the transport of long chain fatty acids into the mitochondria, a critical component of beta-oxidation, the process of converting fats to energy.

Before fatty acids can be attached to a glyceride backbone (e.g., triglycerides) they must first be converted to a CoA thioester. The acyl groups can then bond with the hydroxy group of glycerol. Additionally, the biosynthesis of phospholipids (phosphatidylcholine, ethanolamine, serine, inositol, cardiolipin), as well as plasmalogen, sphingenin, and ceramide, require CoA.

Toxicology and Dosage

Animal studies have documented the low toxicity and safety of pantethine. Although digestive disturbances have occasionally been reported in the literature, the majority of researchers have commented on the complete freedom from side effects and subjective complaints experienced by individuals taking pantethine.

The most common oral dosage used in the treatment of dyslipidemia has been 300 mg three times per day. Higher dosages can be utilized; however, in the majority of individuals this seems to be unnecessary. When utilizing pantethine for other clinical conditions, although information on dosage is limited, a similar schedule is advised.

Conclusion

Pantethine is a metabolically active substrate for CoA and ACP. Because it bypasses several of the enzymatic reactions required for incorporation of pantothenic acid into these molecules, pantethine is capable of exerting a therapeutic effect in conditions where pantothenic acid is ineffective.

Pantethine contains a sulfhydryl (SH) group from a cysteine derivative, while pantothenic acid must be supplied with this SH group prior to having vitamin activity. In vivo, availability of cysteine and SH groups is probably the limiting factor preventing biosynthesis of coenzymes from pantothenic acid. Pantethine offers a significant biochemical advantage by avoiding the need for this endogenous supply of cysteine.

Pantethine has consistently demonstrated an ability to favorably impact lipid parameters in a wide variety of clinical situations. Pantethine administration has been shown to favorably affect platelet lipid composition and cell membrane fluidity. Although supplementation with pantethine should not be expected to reverse existing opacities, administration has successfully prevented experimentally induced cataract formation. Evidence suggests pantethine might be beneficial in the treatment of hepatitis A. In addition to having lipotropic activity, pantethine seems to be very effective in reducing peroxidative damage and enhancing hepatic enzyme function. Pantethine might be capable of enhancing the function of the adrenal cortex; however, more research is needed to ascertain the exact nature of its impact on the adrenal gland and glucocorticoid production in humans. Clinical results of pantethine supplementation are impressive, and because the coenzymes which utilize pantethine for their metabolic activity are utilized in over 70 biochemical reactions affecting a wide variety of cellular functions, it is very likely that only the tip of the iceberg of the therapeutic potential of pantethine has been discovered.

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