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Evidence for altered methionine methyl-group utilization in the diabetic rat's brain

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Abstract

The methionine (MET) derivative, S-adenosylmethionine (SAM), provides methyl-groups for methylation reactions in many neural processes. In rats made diabetic with streptozotocin (SZ), brain SAM levels were generally lower (10–20%) than in controls, with a constant decrease being observed five weeks after onset of diabetes. This decrease in SAM levels may be due to reduced precursor (MET) availability because greatly elevating plasma MET concentrations in SZ diabetic rats by dietary manipulation increased their neural SAM concentrations to be approximately or even greater than (5–20%) those of controls. In contrast, neural levels of SAM's demethylated product, S-adenosylhomocysteine (SAH), were reduced to a greater extent (17–44%) than SAM levels in all groups of SZ diabetic rats independent of their plasma MET concentrations or brain SAM levels. This indicates that the decrease in SAH levels is not simply due to substrate (SAM) restriction. These changes in MET metabolites appear to be a general effect of diabetes rather than a non-pancreatic side-effect of SZ, because genetically diabetic BB Wistar rats also exhibited reduced brain SAM (25%) and brain SAH (46%) levels. These results indicate that methyl-groups from MET are handled differently in the brain of the diabetic rat, which considering the variety and importance of neural methylation reactions, could have important consequences for the diabetic.

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Abbreviations

MET:

methionine

SAM:

S-adenosylmethionine

SAH:

S-adenosylhomocysteine

SZ:

streptozotocin

BBW:

BB Wistar

LNAA:

large neutral amino acids

BCAA:

branchedchain amino acids

MET:BCAA:

methionine to branched-chain amino acid ratio

MET:LNAA:

methionine to large neutral amino acid ratio

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Authors and Affiliations

  1. Dept. of Nutritional Sci., Faculty of Medicine, University of Toronto, M5S 1A8, Toronto, Ontario, Canada

    J. R. Dyer & C. E. Greenwood

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  1. J. R. Dyer
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  2. C. E. Greenwood
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Dyer, J.R., Greenwood, C.E. Evidence for altered methionine methyl-group utilization in the diabetic rat's brain. Neurochem Res 13, 517–523 (1988). https://doi.org/10.1007/BF00973290

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