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Juvenile-Specific Localization and Accumulation of a Rhamnosyltransferase and Its Bitter Flavonoid in Foliage, Flowers, and Young Citrus Fruits.

1-2-Rhamnosyltransferase catalyzes the production of disaccharide-flavonoids that accumulate to 75% of dry weight. Vast energy is expended in a short time span to produce these flavonoids. The highest rhamnosyltransferase activities and immunodetected concentrations were observed in early development of Citrus grandis (pummelo), coinciding with up to 13% of fresh weight as naringin. The concentration of naringin in leaves, petals, receptacles, filaments, albedo, and flavedo drops drastically during development and correlates directly with a decrease in the activity and amounts of 1-2-rhamnosyltransferase. Anthers had minute rhamnosyltransferase activities and low concentrations of naringin. Conversely, high 1-2-rhamnosyltransferase activity and naringin concentrations appeared in both young and mature ovaries, as well as in young fruits. The total amounts of naringin in mature leaves decreased without detectable in vitro degradation of naringin in leaves. There was still a net accumulation of naringin in the albedo and flavedo of older fruit even though these tissues had only traces of 1-2-rhamnosyltransferase. Traces of enzyme synthesis in fruits, or import of the product from leaves, may explain the net accumulation of naringin in growing fruits. Unlike the late-expressed genes for glycosyltransferases in anthocyanin biosynthesis, the rhamnosyltransferases from Citrus are active only in juvenile stages of development.

Journal Article↗

Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man.

1. The effects of grapefruit juice and naringenin on the activity of the human cytochrome P450 isoform CYP1A2 were evaluated using caffeine as a probe substrate. 2. In vitro naringin was a potent competitive inhibitor of caffeine 3-demethylation by human liver microsomes (Ki = 7-29 microM). 3. In vivo grapefruit juice (1.2 l day-1 containing 0.5 g l-1 naringin, the glycone form of naringenin) decreased the oral clearance of caffeine by 23% (95% CI: 7%-30%) and prolonged its half-life by 31% (95% CI: 20%-44%) (n = 12). 4. We conclude that grapefruit juice and naringenin inhibit CYP1A2 activity in man. However, the small effect on caffeine clearance in vivo suggests that in general the ingestion of grapefruit juice should not cause clinically significant inhibition of the metabolism of other drugs that are substrates of CYPIA2.

Adult↗

Wilhelm Bitter.

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Germany, West↗

Consumption of sweet, salty, sour, and bitter solutions by selectively bred alcohol-preferring and alcohol-nonpreferring lines of rats.

To determine whether selective breeding for high or low oral ethanol consumption is associated with different preferences for nonpharmacological solutions with various flavors, the oral intake of a range of concentrations of sucrose (0.5-64.0 g/100 ml), NaCl (0.025-3.2 g/100 ml), citric acid (0.008-2.048 g/liter), and sucrose octaacetate (0.002-0.512 g/liter) was studied in alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. Separate groups of 7-8 rats from each line were tested for consumption of each of the four flavors. The flavored solutions were presented continuously with water and food always available, and the concentrations were doubled every 48 hr. Although rats from both lines showed a strong preference for the sucrose solutions, P rats consumed greater amounts than NP rats [F(7,98) = 5.57, p < 0.001]. Rats of the P line drank less of the NaCl solutions than NP rats [F(7,98) = 3.88, p < 0.001], but the effect was not as robust as the line differences seen with sucrose. The P and NP rats did not differ in citric acid or sucrose octaacetate intake at any of the concentrations tested. Selective breeding for high oral ethanol preference appears to be positively associated with consumption of sweet solutions and negatively associated with intake of salty solutions.

Alcohol Drinking↗

Aminosalicylates and colorectal cancer in IBD: a not-so bitter pill to swallow.

Inflammatory bowel disease (IBD) is associated with an increased risk of developing intestinal cancer at sites of chronic inflammation. Aminosalicylates, including both sulfasalazine and mesalamine, are the most commonly prescribed anti-inflammatory agents prescribed in IBD. On balance, the body of literature to date suggests that aminosalicylates confer some protection against the development of colonic neoplasia in patients with IBD and in a variety of models, including in the noninflamed gut. This latter observation implies that aminosalicylates may be of chemopreventive value in normal as well as IBD individuals. The current review examines and gives an overview of the evidence from a variety of sources, including epidemiological, in vivo and in vitro studies that have investigated the potential anticancer effects of aminosalicylates.

Aminosalicylic Acids↗

Effects of gymnemic acid on the chorda tympani proper nerve responses to sweet, sour, salty and bitter taste stimuli in the chimpanzee.

In man gymnemic acid is able to abolish the sweet taste. Also in man, the neural correlate of that effect is a disappearance of the response to sweet stimuli in the taste nerves, as indicated by the observations of Diamant et al. (1965). Although a variety of other mammals also show neural responses to sweet-tasting compounds, the corresponding effect of gymnemic acid has not been demonstrated. This study presents chorda tympani proper nerve recordings from the chimpanzee before and after gymnemic acid. On the chimpanzee tongue, application of 2 ml gymnemic acid (3-10 mg X ml-1 for 3-4 min) completely abolished the taste responses to 0.0035 M acesulfam-K, 0.0018 M aspartame, 0.015 M D-tryptophan, 0.02% monellin, and 0.02% thaumatin, reduced by 75% the response to 0.3 M sucrose, and by 50% that of 0.76 M xylitol. No decrease was recorded in the responses to 0.001 M quinine, 0.1 M NaCl, 0.02 and 0.04 M ascorbic acid, 0.02 and 0.04 M citric acid. The response to the sweeteners recovered with time and the recovery was complete or nearly complete after one and a half hours. It was also found that after application of 2 ml miraculin, 3 mg X ml-1 for 3 min to the tongue the neural response to acids was about 1.5 times as large as before. Gymnemic acid applied before miraculin prevented this enhancement and gymnemic acid after miraculin depressed the enhancement by miraculin of the response to citric and ascorbic acid.

Animals↗

The bitter pill.

Fundamentally new approaches to birth control--for example, a male pill, a once-a-month menses inducer, and an antifertility vaccine--cannot be realized before the next century, and then only if the virtual withdrawal of the pharmaceutical industry from this field can be reversed. Major changes in product liability would be the most significant incentive.

Animals↗