REPLY

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JOP. J Pancreas (Online) 2010 Nov 9; 11(6):651.

Reply to 'Some More Comments on Folate Deficiency in Chronic Pancreatitis'

Joan M Braganza

Royal Infirmary. Manchester, United Kingdom

Dear Sir,

Dr Wagner’s erudite comments in the present issue of JOP. J Pancreas (Online) [1] further illuminate the complex interactions between micronutrient deficiency, electrophilic stress, and disrupted methionine homeostasis, that together seem to precipitate chronic pancreatitis by impairing the exocytosis of zymogen granules from pancreatic acinar cells [2, 3].

Dr Wagner’s studies and arguments [1] underline the essentiality of methyl moieties for exocytosis. They act directly (by carboxymethylating small G proteins in the apical membrane), and indirectly by incorporation into phosphatidylcholine for granule membrane-apical membrane fusion during the exocytosis process. Dietary methionine is the main source of methyl groups, delivered via its first metabolite S-adenosylmethionine (SAM). Dietary folic acid - in concert with vitamin B12 and ascorbic acid (bioactive fraction of vitamin C) - facilitates methionine regeneration from homocysteine. Dietary betaine and choline provide pre-formed methyl groups.

The ancillary methyl sources (folic acid, betaine, choline) could determine whether or not exocytosis can proceed when methionine intake falls short of need, as it does (along with insufficiency of vitamin C) in chronic pancreatitis wherein demand increases due to cytochrome P450 induction [4], with increased release of reactive oxygen and xenobiotic species [2]. The vulnerability to the ensuing electrophilic stress of enzymes such as that which catalyses the conversion of methionine to SAM [5] rationalizes both the surge in circulating level of methionine and SAM in an acute exacerbation of chronic pancreatitis [6, 7], and evidence that the methionine metabolic pathway remains fractured thereafter [8]. A supplement of methionine (or SAM) plus vitamin C curbs attacks, and additional choline (theoretically betaine alternatively [1]) is helpful when treatment fails [2]. All these observations indicate the clinical relevance of methionine plus/minus choline-deficient dietary models of pancreatic injury [9, 10, 11].

References

  1. Wagner C. Some more comments on 'Folate deficiency in chronic pancreatitis'. JOP. J Pancreas (Online) 2010; 11:646-7. [More details]

  2. Braganza JM, Dormandy TL. Micronutrient therapy for chronic pancreatitis: rationale and impact. JOP. J Pancreas (Online) 2010; 11:99-112. [More details]

  3. Girish BN, Vaidyanathan K, Rao NA, Rajesh G, Reshmi S, Balakrishnan V. Chronic pancreatitis is associated with hyperhomocysteinemia and derangements in transsulfuration and transmethylation pathways. Pancreas 2010; 39:e11-6. [More details]

  4. Uden S, Acheson DW, Reeves J, Worthington HV, Hunt LP, Brown S, Braganza JM. Antioxidants, enzyme induction, and chronic pancreatitis: a reappraisal following studies in patients on anticonvulsants. Eur J Clin Nutr 1988; 42:561-9. [More details]

  5. Corrales F, Giménez A, Alvarez L, Caballería J, Pajares MA, Andreu H, et al. S-adenosylmethionine treatment prevents carbon tetrachloride-induced S-adenosylmethionine synthetase inactivation and attenuates liver injury. Hepatology 1992; 4:1022-7. [More details]

  6. Mårtensson J, Bolin T. Sulfur amino acid metabolism in chronic relapsing pancreatitis. Am J Gastroenterol 1986; 81:1179-84. [More details]

  7. Uden S, Schofield D, Miller PF, Day JP, Bottiglier T, Braganza JM. Antioxidant therapy for chronic pancreatitis: biochemical profiles in a placebo-controlled trial. Aliment Pharmacol Ther 1992; 6:229-40. [More details]

  8. Syrota A, Dop-Ngassa M, Paraf A. 11C-L-methionine for evaluation of pancreatic exocrine function. Gut 1981; 22:907-15. [More details]

  9. Kahn DE, Carlson AB. On the mechanism of experimentally induced ethionine pancreatitis. Ann Surg 1959; 150:42-7. [More details]

  10. Veghelyi PV, Kemeny TT, Pozsonyi J, Sós J. Dietary lesions of the pancreas. Am J Dis Child 1950; 79:658-65. [More details]

  11. Lombardi B. Influence of dietary factors on the pancreatotoxicity of ethionine. Am J Pathol 1976; 84:633-48. [More details]

Article in PDF format

Received September 9th, 2010

Key words Ascorbic Acid, Exocytosis; Folic Acid; Methionine

Abbreviations SAM: S-adenosylmethionine

Conflict of interest None

Correspondence
Joan M Braganza
c/o Jenny Parr
Core Technology facility, 3rd floor
45 Grafton Street
Manchester M13 9NT
United Kingdom
Phone: +44-161.275.1191
Fax: +44-161.275.1183
E-mail: jenny.parr@manchester.ac.uk

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