Chiasma-induction and tyrosine metabolism in locusts

The production of a gregarization pheromone has been postulated in locusts, with effects on melanization of the hopper cuticle and increased chiasma frequency during meiosis in the adult on crowding or gregarization. Lack of chiasma-inducing effect of the pheromone on albino strains is correlated with the absence or deficiency of some of the products of the metabolic pathways of tyrosine. Some of these products, commercially obtainable, are the amino acids phenylalanine and tyrosine leading to both the melanization and sclerotization pathways; dopamine formed from dopa in the lastnamed pathway; three products of dopamine i.e. protocatechuic acid, noradrenaline and adrenaline. The injection of solutions of these metabolites into the haemolymph of solitary hoppers has shown that only dopa to some extent but noradrenaline to a large extent are effective in raising chiasma frequency in solitarised individuals of normal-coloured strains of Locusta, while in two albino strains, which differ genetically, the injection of dopa, dopamine, protocatechuic acid and noradrenaline proved effective; phenylalanine was effective in only one of these albino strains, while adrenaline was effective in neither. The chiasma-inducing effect of noradrenaline, common to the three strains, is accompanied in the normal-coloured strain by a greater retention of dark coloration during solitarization and by some attainment of the crowded type of morphometric ratios which is a third physical criterion of gregarization. The genetic blocks to the physical criteria of gregaria in the albino strains lie at the immediate level of dopa production or previous to this reaction; it may be construed that such a block in the solitaria of normal-coloured strains also lies at this early level, in this case being induced by too low a pheromone concentration.     

Phenylalanine and tyrosine metabolism in the facultative methylotroph Nocardia sp. 239

Nocardia sp. 239 is able to use l-tyrosine and both d- and l-phenylalanine as carbon-, energy- and nitrogen sources for growth. The catabolism of these compounds is by way of (4-hydroxy)phenylpyruvate and (4-hydroxy)-phenylacetate as intermediates and the pathways merge at the level of homogentisate. The conversion of the amino acids into (4-hydroxy)phenylpyruvate is catalyzed by an inducible NAD-dependent phenylalanine dehydrogenase and l-tyrosine aminotransferase, respectively. Incubation of the organism in media with l-phenylalanine plus phenyl-pyruvate resulted in diauxic growth, with phenylpyruvate used first. Phenylalanine dehydrogenase activity cold only be detected after depletion of phenylpyruvate, in the ensuing second growth phase on l-phenylalanine. During growth on phenylalanine plus methanol, low levels of phenylalanine dehydrogenase were detected and this resulted in simultaneous utilization of the two substrates. Following diepoxyoctane treatment, mutants of Nocardia sp. 239 affected in phenylalanine and phenylpyruvate degradation were isolated. Double mutants blocked in both phenylalanine dehydrogenase and phenylpyruvate decarboxylase completely failed to catabolize phenylalanine. The absence of these enzymes did not affect growth on tyrosine.Abbreviations RuMP ribulose monophosphate - EMS ethylmethanesulphonate - NTG N-methyl-N-nitro-N-nitrosoguanidine     

Decarboxylation to tyramine is not a major route of tyrosine metabolism in mammals.

We have examined the question of the contribution of decarboxylation of tyrosine to tyramine to the overall metabolic fate of tyrosine in mammalian organisms. Since this enzymatic step is independent of oxygen while the loss of the carboxyl group via the transaminase-hydroxylase major pathway is oxygen dependent, we studied the rate of ¹⁴CO₂ release from tyrosine in the presence and absence of oxygen. These studies indicate that a trivial amount of tyrosine is processed by direct decarboxylation to tyramine, even at high substrate levels. Tyrosine metabolism precedes via the well-established pathway which is launched by transamination.     

Effect of hypercapnia on tyrosine and tryptophan metabolism]

Experiments were conducted on albino rats; it was revealed that an increase in CO2 content in the inspired air (3.8%) caused disturbances in tyrosine and tryptophane metabolism. The activity of tyrosine-aminotranspherase and of tryptophane-oxygenase proved to increase in the liver; blood serum displayed a reduced concentration of free tyrosine and free total tryptophane, but the level of free tryptophane obtained by dialysis proved to rise. A possible significance of these deviations in endogenous blastomogenesis is discussed.     

The effect of ovariectomy on phenylalanine and tyrosine metabolism

Summary Although the regulatory activity of steroid hormones on amino acid metabolism has been described, no information is published on the effect of ovariectomy. We studied the influence of ovariectomy in Wistar rats determining the amino acids phenylalanine and tyrosine in liver, kidney, plasma and urine. 32 animals were used in the study, 12 animals were sham operated, 9 animals were ovariectomized and 11 rats were ovariectomized and supplemented with estradiol. No quantitative changes were detected comparing liver and kidney phenylalanine and tyrosine between the groups (sham operated rats liver phenylalanine 2,53nM/mg ± 1,07; liver tyrosine 1.95nM/mg ± 0.92; kidney phenylalanine 2.16nM/mg ± 0.53; kidney tyrosine 1.80nM/mg ± 0.39. Ovariectomized rats showed liver phenylalanine 3.07nM/mg ± 1.14; liver tyrosine 2.63nM/mg ± 1.01; kidney phenylalanine 2.30 nM/mg ± 0.74; kidney tyrosine 1.93nM/mg ± 0.63. Ovariectomized and estradiol supplemented rats presented with liver phenylalanine 2.84nM/mg ± 1.40; liver tyrosine 2.35nM/mg ± 1.28; kidney phenylalanine 1.91nM/mg ± 0.26, kidney tyrosine 1.67nM/mg ± 0.23.). When, however, the phenylalanine/tyrosine ratio in the liver was evaluated, ovariectomized rats showed a significant decrease of the quotient (p = 0.001). The phenylalanine/tyrosine ratio was restored by estradiol replacement. Our findings show that phenylalanine and tyrosine metabolism is under estradiol control. The effect on the metabolic changes could be mediated by enzyme systems as phenylalanine hydroxylase, tyrosine hydroxylase and tyrosine aminotransferase. Our results would be compatible with previous reports on the stimulatory effect of estradiol on these enzymes. The kidney phenylalanine/tyrosine ratio was unaffected by ovariectomy and/or estradiol replacement which can be easily explained by different pools, enzyme activities, filtration/reabsorption effects, etc.The urinary P/T ratio was decreased by ovariectomy and restored by estradiol replacement indicating endocrine control of renal reabsorption and secretion mechanisms.     

The contribution of phenylalanine to tyrosine metabolism in vivo. Studies in the post-absorptive and phenylalanine-loaded rat.

1. Rates of appearance and oxidation of plasma L-leucine, L-phenylalanine and L-tyrosine, as well as conversion of plasma phenylalanine into plasma tyrosine, were determined in 90-120 g rats after overnight starvation and while receiving 115-120 mumol of L-phenylalanine/h. 2. In the post-absorptive state, plasma tyrosine and phenylalanine appearances were similar, despite the fact that 22% of plasma tyrosine appearance could be attributed to the hydroxylation of phenylalanine. 3. A constant infusion of 115-120 mumol of L-phenylalanine/h did not significantly alter plasma leucine kinetics, but increased appearance of plasma phenylalanine and tyrosine. The percentage of phenylalanine and tyrosine appearance that was oxidized increased from 12.1% and 24.4% to 37.3% and 48.0% respectively. In phenylalanine-loaded rats, 72% of plasma tyrosine appearance could be attributed to the conversion of phenylalanine. 4. Whole-body tyrosine oxidation measured from a continuous infusion of either L-[14C]tyrosine or L-[14C]phenylalanine differed by 165%. 5. It can be concluded that, in the post-absorptive state, phenylalanine hydroxylation makes a substantial contribution to the plasma appearance of tyrosine and is significantly increased when phenylalanine is administered. The disposal of excess infused phenylalanine is a result of a greater percentage of plasma phenylalanine being converted into tyrosine and a greater proportion of tyrosine being further oxidized. However, apparent tyrosine oxidation rates estimated from plasma tyrosine specific radioactivities and appearance of expired 14CO2 during administration of [14C]tyrosine are underestimates of true rates, in part because tyrosine generated from phenylalanine hydroxylation is catabolized without freely equilibrating with the plasma compartment.     

NAD metabolism and induction of tyrosine aminotransferase in the rat

The relationship between the NAD-metabolism and the induction of the tyrosine aminotransferase was studied. The content of NAD+ + NADH differs markedly from organ to organ. The highest values can be found in the liver. In intact animals tryptophan leads to an increase of NAD in liver and kidney, but not in brain and spleen. Nicotinamide, on the other hand, induces NAD synthesis in all the organs tested. In adrenalectomized animals, however, there is practically no rise of the NAD content after application of tryptophan contrary to the effect of nicotinamide. The enzyme tyrosine aminotransferase can be induced in intact animals by nicotinamide and tryptophan. This effect is much less pronounced in adrenalectomized animals. In adrenalectomized animals the induction of the tyrosine aminotransferase by tryptophan is markedly elevated by caffeine and theophylline. Under these conditions there is a significant increase of the NAD content as well. The tryptophan promoted induction of the tyrosine aminotransferase is influenced by inhibitors of the ADPR-transferase. The data presented give further evidence that the NAD adenoribosylation metabolism is involved in the induction of the tyrosine aminotransferase.     

Control of erythrocyte metabolism by redox-regulated tyrosine phosphatases and kinases

Summary We wish to elaborate a novel mechanism of metabolic regulation mediated by cytoplasmic tyrosine phosphatases and kinases. Briefly we propose that phosphofructokinase, aldolase, and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) bind reversibly to the N-terminus of the cytoplasmic domain of band 3. Once the enzymes are bound, they are inhibited; however, upon release they are restored to full activity. We demonstrate that control of enzyme binding and consequently control of substrate flow down the pathway is executed by phosphorylation of Tyr 8 and Tyr 21 within the glycolytic enzyme binding site at the N-terminus of band 3. This phosphorylation results in obstruction of enzyme binding, leading to enzyme activation. Importantly, the tyrosine kinase that phosphorylates band 3 is activated by oxidation, while the tyrosine phosphatase that dephosphorylates band 3 is inhibited by the same redox changes. Consequently, treatment of red cells wih oxidants such as H₂O₂ and ferricyanide can enhance both tyrosine phosphorylation of the N-terminus of band 3 and glycolysis in a coordinate manner. Because oxidant entry into the cell is not essential, a plasma membrane electron transport pathway is believed to mediate the oxidant's effects.