Metabolic Control of Avocado Fruit Growth (Isoprenoid Growth Regulators and the Reaction Catalyzed by 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase).

The effect of isoprenoid growth regulators on avocado (Persea americana Mill. cv Hass) fruit growth and mesocarp 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity was investigated during the course of fruit ontogeny. Both normal and small-fruit phenotypes were used to probe the interaction between the end products of isoprenoid biosynthesis and the activity of HMGR in the metabolic control of avocado fruit growth. Kinetic analysis of the changes in both cell number and size revealed that growth was limited by cell number in phenotypically small fruit. In small fruit a 70% reduction in microsomal HMGR activity was associated with an increased mesocarp abscisic acid (ABA) concentration. Application of mevastatin, a competitive inhibitor of HMGR, reduced the growth of normal fruit and increased mesocarp ABA concentration. These effects were reversed by co-treatment of fruit with mevalonic acid lactone, isopentenyladenine, or N-(2-chloro-4-pyridyl)-N-phenylurea, but were not significantly affected by either gibberellic acid or stigmasterol. However, stigmasterol appeared to partially restore fruit growth when co-injected with mevastatin in either phase II or III of fruit growth. In vivo application of ABA reduced fruit growth and mesocarp HMGR activity and accelerated fruit abscission, effects that were reversed by co-treatment with isopentenyladenine. Together, these observations indicate that ABA accumulation down-regulates mesocarp HMGR activity and fruit growth, and that in situ cytokinin biosynthesis modulates these effects during phase I of fruit ontogeny, whereas both cytokinins and sterols seem to perform this function during the later phases.

Cytochrome P-450-dependent hydroxylation in migraine.

The hypothesis was tested that an acute oxidation deficiency related to potential dietary trigger factors plays a role in the migraine attack. Migraine sufferers (14F and 4M), fulfilling the criteria for migraine with and without aura according to the classification of the International Headache Society, were coadministered oral mephenytoin (100 mg) and debrisoquine (10 mg) during the initial phase of a typical migraine attack. This was repeated during a period without migraine. The hydroxylation of mephenytoin and debrisoquine hydroxylation did not differ during and without the migraine attack. We conclude that hydroxylation, via cytochrome P-450 (2D6, 2C8 and 9), is not reduced during the migraine attack. The results do not support the hypothesis that oxidation deficiency is involved in the pathophysiology of migraine.

Polymorphic debrisoquin hydroxylation in 757 Swedish subjects.

The metabolic ratios (MRs) between debrisoquin and 4-hydroxydebrisoquin in urine after a single oral dose of 10 mg debrisoquin were bimodally distributed in 757 healthy, white Swedish volunteers. Forty-one subjects (5.4%) had an MR greater than 12.6 and were classified as slow debrisoquin hydroxylators. The MR was reproducible in urine stored at +8 degrees C for 1 week and at -20 degrees C over a period of 5 years. Collection intervals of 6 or 12 hours gave the same MR. Intraindividual repeatability of the debrisoquin phenotyping test was established in 37 subjects examined twice at least 2 weeks apart. The calculated frequency of the single allele that is believed to control deficient debrisoquin hydroxylation is similar among white Swedish people, as among other white groups examined so far; however, it is significantly different from the frequency in certain Oriental groups. Detailed comparisons of the prevalence of slow debrisoquin hydroxylation in different ethnic groups are not possible due to shortcomings in current epidemiologic techniques used (small materials, the location of the antimode distinguishing rapid and slow hydroxylators unknown, and family studies missing).