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Impact of mineral micronutrients upon COMT expression and
activity in rat liver and adrenal glands
Pedro Bastos 1,2 , João Araújo 1 , Maria João Martins 1 , Fátima Martel 1 , Laura Ribeiro 1
1 Department of Biochemistry, Faculty of Medicine, University of Porto, Portugal.
2 Department of Biology, School of Sciences, University of Minho, Portugal.
COMT is a magnesium dependent enzyme that catalyzes the methylation of catechol
substrates, as estrogens and polyphenols, performing a most important role in catecholamine
metabolism, mainly in adrenaline.[1] These amines play key roles in the regulation of
numerous physiological processes and are being implicated in an everexpanding array of
neurological, psychiatric, endocrine, and cardiovascular disorders. Magnesium, COMT
cofactor, although essential for several cell reactions, has a dietary intake in much of the
Western World population inferior to the recommended dietary allowances.[2] A relationship
between low COMT activity and various disorders has been suggested, and much attention
devoted to the impact of COMT polymorphisms on cardiovascular health.[3]
The aim of this study was to test the effect of a magnesium-deficient diet and of a high
magnesium intake in COMT activity. The effect of these different diets on COMT expression
was also evaluated.
Adult Wistar rats (weighting 270-300g) were treated for 7 weeks with three different diets
(group 1: standard; group 2: high sodium, low magnesium; group 3: high sodium, high
magnesium). At the end of the treatment, COMT expression in the liver and adrenal glands was
evaluated by RT-PCR, and COMT activity determined, by HPLC, in the same tissues, by
measuring metanephrine formation after exposure to adrenaline. Statistical analysis were
performed by one-way analysis of variance (ANOVA) followed by Newman-Neuls test for
multiple comparisons. Arithmetic means are given with S.E.M..
Liver COMT activity showed significant differences between the high magnesium intake and
the control groups (n= 4-6, p< 0.05), with a maximal enzyme activity 1.3-fold higher in the
high magnesium intake group (Vmax: 26.5 ± 2 nmol/h/mg protein) compared with the control
(Vmax: 20.0 ± 1.4 nmol/h/mg protein), as well as a 1.6-fold increased affinity towards
adrenaline (Km: 56.56 ± 18.03 vs 88.63 ± 22.40 µM). COMT mRNA expression in adrenal
glands significantly decreased with high magnesium intake, being about 46% lower in this
group compared with the standard diet group (n = 4-6, p< 0.05), while in the liver it remained
unchanged in response to the three different diets (n = 6).
These results suggest that diet may impact COMT expression and activity.
References:
[1] Männistö, P.T., Kaakkola, S. (1999). Catechol-O-methyltransferase (COMT): biochemistry,
molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors.
Pharmacological Reviews, 51: 593-628.
[2] Altura, B.M., Altura, B.T. (1996). Role of magnesium in patho-pysiological processes and the
clinical utility of magnesium ion selective electrodes. Scandinavian Journal of Clinical and Laboratory
Investigation, 56: 211-234.
[3] Annerbrink, K et al. (2008). Catechol O-methyltransferase val158-met polymorphism is associated
with abdominal obesity and blood pressure in men. Metabolism Clinical and Experimental, 57: 708-
711.
88 3 rd meeting of young researchers at UP