Sulphur amino acid metabolism, oxidative stress and pancreatitis

Abstract

The observation that mice fed a diet that blocks the recycling and metabolism of methionine develop fulminant pancreatitis, attests to the dependence of the pancreatic acinar cell on methionine transsulphuration.

S-adenosylmethionine (SAMe), the first intermediate of transsulphuration, is the principle metabolic methyl group donor.  Glutathione (GSH) a final product of transsulphuration is a vital intracellular antioxidant.  N-acetylcysteine (NAC), an antioxidant in its own right potentially bolsters GSH levels.  Thus, the combination of SAMe and NAC could be expected to ameliorate and/or accelerate recovery from acute pancreatitis.  However, intravenous SAMe and NAC for the first 24 hours of acute pancreatitis, proved to be of no advantage over optimal conventional care in a randomised trial.  Low blood folate levels were identified as a potential for treatment failure, as also was vitamin C.

Plasma methionine concentration was similar in healthy controls and patients with quiescent recurrent acute (RAP) or chronic (CP) pancreatitis.  Oral loading and methionine or NAC exposed no differences between these groups in methionine pharmacokinetics, or the concentration of (i) amino acids whose metabolism is linked with methionine or (ii) transsulphuration intermediates, except for plasma GSH, which is low in pancreatitis.  Serum selenium and vitamin C were low in patients with pancreatitis, as was urinary inorganic sulphate excretion in CP.  These vitamin deficiencies are corrected within 10 weeks by oral antioxidant supplementation therapy [Bioantox i.q.i.d. PharmaNord] (AOT).  AOT did not alter blood levels or pharmacokinetic characteristics of methionine, GSH or other amino acids measured.

Irrefutable evidence implicates oxidative stress and/or a disruption of methionine metabolism in the genesis of pancreatitis.  Further studies to elucidate the mechanisms that initiate and prevent/reverse these metabolic perturbations should facilitate the development of an antioxidant cocktail with prophylactic and therapeutic activity against this condition.

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