VITAMINS

This article reviews possible preventive effects on cancer by micronutrients on the basis of worldwide epidemiological investigations in humans. Cohort and case-control studies indicate clearly that vegetable and fruit consumption decreases the risk for most sites of cancer. The risk reduction is observed not only for gastrointestinal tract cancers, but also for other sites (e.g. breast) of cancers. Consumption of vitamin C and β-carotene is related to risk reduction. Four large-scale randomized intervention studies have been reported. A study done in Linxian, China indicates that, among various micronutrients administered, β-carotene; vitamin E, and selenium reduced the risk of gastric cancer by 21%. However, a study on US male physicians showed no effects by β-carotene and two other studies on heavy smokers showed some elevated risk for lung cancer. Although more consumption of vegetables and fruits should be recommended to the general public for the prevention of cancer, further extensive investigations are needed to identify truly effective micronutrients contained in vegetables and fruits.

View full abstract

Show abstractHide abstract

Although the reaction catalyzed by aspartate aminotransferase (AAT) has been extensively studied and the Karpeisky-Ivanov mechanism has been widely accepted, there remain many unsolved important problems. These are: 1) Acid-base chemistry of AAT has not been established because of the unusual kinetic behavior at low pH. 2) The exceptionally low pK_a of the Schiff base of AAT makes its reaction mechanism unapplicable to other B_6 enzymes. 3) The role of the enzyme protein in catalysis has not yet been clarified. This review summarizes our recent work that gave solutions to these problems. The rate of disappearance of the Schiff base-protonated enzyme (E_LH^+) upon reaction with aspartate was apparently slower than that of the Schiff base-unprotonated enzyme (E_L). At low pH and low substrate concentrations, this difference was found to come from the relatively slow exchange of proton between the PLP-Lys258 Schiff base and the solvent. With increasing pH and aspartate concentration, the rate of disappearance of E_LH^+ became larger than taht expected from the model in which EL is the sole reactive species. The deviation was excellently explained by assuming the association of E_LH^+ and aspartate with unprotonated amino group (S) in addition to the association of E_L and SH^+. The newly discovered route (E_LH^+-S) seems to be the main route in B_6 enzymes which have only the E_LH^+ structure. The establishment of the pH study in the transient kinetics of AAT enabled us to analyze the reaction of AAT with a substrate analogue 2-methylaspartate on a wide range of pH. The result showed that the Schiff bases in the Michaelis complex and the external aldimine complex were partially protonated, irrespective of the solvent pH. The intrinsic pK_a values of the Schiff base, estimated from the fraction of the protonation, was found to increase progressively from the unliganded enzyme to the external aldimine complex. A novel model for the modulation of the Schiff base pK_a, in which the imine-pyridine torsion of the Schiff base regulates the basicity of the Schiff base, was proposed and was supported by the spectroscopic study on the Lys258-side-chain-fragmented AAT. The strain of the protonated Schiff base is interpreted to enhance the catalytic ability of the enzyme by increasing the energy level of the free enzyme plus substrate at neutral pH relative to the transition state. Combining these observations altogether, a refined reaction mechanism of AAT was proposed.

View full abstract

Download PDF (1361K)

On the basis of the school lunch menus in the three cities in Osaka prefecture, a supply of fat, fatty acids and vitamin E was calculated according to the "Fat soluble nutrient composition in Japan". There was no difference in supply conditions with respect to fats, fatty acids and vitamin E among three cities. 1) Energy percent occupied by fat supply was 31.2%. According to the standard energy percent from fat (25〜30%), only 32 of 99 samples were within the standard range, while 52 exceeded the range and 7 showed more than 40% on the energy ratio. 2) The main sources of fat supply consisted of 35%,18% and 19% from milk, oil and meat respectively, and those occupied 72% of total fat supply. Additionally, milk and meat formed 75% of total supply of the saturated fatty acids. Energy supply from poly-unsaturated fatty acid (PUFA) was 20% of that from total fat. The ratio of saturated, mono-unsaturated and poly-unsaturated fatty acids was 1.2:1.0:0.6 on the fatty-acid composition, and that differed from the Japanese dietary standard ratio of 1:1.5:1. 3) Vitamin E supply was 2.2 mg per a lunch, which is 37% of 6 mg(daily dose) corresponding to the Japanese recommended dose as adjusted with age. The vitamin E/PUFA ratio was 0.57.

View full abstract

Register with J-STAGE for free!