scholarly journals Effect of glucagon on phenylalanine metabolism and phenylalanine-degrading enzymes in the rat

1974 ◽  
Vol 142 (2) ◽  
pp. 231-245 ◽  
Author(s):  
Larry M. Brand ◽  
Alfred E. Harper
Keyword(s):  
Urinary Excretion ◽  
Oxidation Rate ◽  
Phenylalanine Hydroxylase ◽  
Dihydropteridine Reductase ◽  
Aminotransferase Activity ◽  
Hydroxylase Activity ◽  
Phenylalanine Metabolism ◽  
Rate Limiting ◽  
Reduced State

Glucagon administered subcutaneously to rats for 10 days had no significant effect on liver phenylalanine hydroxylase activity, but induced liver dihydropteridine reductase more than twofold. In rats administered a phenylalanine load orally, glucagon treatment stimulated oxidation and depressed urinary phenylalanine excretion. These responses could not be related to an effect of glucagon on hepatic tyrosine–α-oxoglutarate aminotransferase activity. Even in rats with phenylalanine hydroxylase activity depressed to 50% of control values by p-chlorophenylalanine administration, glucagon treatment increased the phenylalanine-oxidation rate substantially. Although hepatic phenylalanine–pyruvate aminotransferase was increased tenfold in glucagon-treated rats, glucagon treatment did not increase urinary excretion of phenylalanine transamination products by rats given a phenylalanine load. Glucagon treatment did not affect phenylalanine uptake by the gut or liver, or the liver content of phenylalanine hydroxylase cofactor. It is suggested that dihydropteridine reductase is the rate-limiting enzyme in phenylalanine degradation in the rat, and that glucagon may regulate the rate of oxidative phenylalanine metabolism in vivo by promoting indirectly the maintenance of the phenylalanine hydroxylase cofactor in its active, reduced state.

scholarly journals Metabolism of phenylalanine in mice homozygous for the gene ‘dilute lethal’

1970 ◽  
Vol 119 (5) ◽  
pp. 895-903 ◽  
Author(s):  
L. I. Woolf ◽  
A. Jakubovic ◽  
F. Woolf ◽  
P. Bory
Keyword(s):  
Natural History ◽  
Phenylalanine Hydroxylase ◽  
Disease Process ◽  
Particulate Fraction ◽  
Hydroxylase Activity ◽  
Phenylpyruvic Acid ◽  
History Of

Mice homozygous for dl have been suggested as models for phenylketonuria. We found: (1) the concentration of phenylalanine in the blood was normal at all ages examined; (2) phenylalanine hydroxylase activity in the liver in vitro equalled that in unaffected littermates; (3) the apparent Km values for phenylalanine and cofactor respectively in dl/dl mice were the same as in their normal littermates; (4) inhibition of the overall reaction by the particulate fraction, excess of substrate, excess of cofactor or phenylpyruvic acid showed no difference between dl/dl mice and their unaffected littermates; (5) phenylalanine injected in vivo had equal, small, effects on phenylalanine hydroxylase activity of the liver measured in vitro in the two groups of mice. An explanation of the findings of other workers, based on the natural history of the disease process, is tentatively put forward.

scholarly journals IN VIVO PHENYLALANINE HYDROXYLASE ACTIVITY

1987 ◽  
Vol 21 (4) ◽  
pp. 346A-346A
Author(s):  
Claude Sansaricq ◽  
Selma E Snyderman ◽  
Ann Arcay
Keyword(s):  
Phenylalanine Hydroxylase ◽  
Hydroxylase Activity

Effect of glucagon on hepatic phenylalanine hydroxylase in vivo

1985 ◽  
Vol 5 (6) ◽  
pp. 463-467 ◽  
Author(s):  
Edel Beirne ◽  
Michael P. Carty ◽  
John Donlon
Keyword(s):  
Phenylalanine Hydroxylase ◽  
High Protein Diet ◽  
Physiological Changes ◽  
Phosphate Content ◽  
Hydroxylase Activity ◽  
Human Phenylalanine Hydroxylase ◽  
Stimulation Of ◽  
Glucagon Concentration

Moderate doses of glucagon (20 μg/kg I.V.) are sufficient to stimulate rat hepatic phenylalanine hydroxylase in vivo. In addition, the stimulation of the tetrahydrobiopterin-dependent phenylalanine hydroxylase activity in livers of animals fed on a high-protein diet has been correlated with an elevated phosphate content. The tetrahydrobiopterin-dependent hydroxylase activity in these animals can be further elevated by glucagon-stimulated phosphorylation. These results indicate that physiological changes in glucagon concentration modulate rat liver phenylalanine hydroxylase activity in vivo. The current understanding of the role of phosphorylation in regulating human phenylalanine hydroxylase is also considered.

High Protein Diet and Phenylalanine Hydroxylase Activities in Rats

Pteridines ◽  
1989 ◽  
Vol 1 (4) ◽  
pp. 235-238 ◽  
Author(s):  
Michael P. Carty ◽  
Edel Beirne ◽  
John Donlon
Keyword(s):  
Rat Liver ◽  
Phenylalanine Hydroxylase ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Casein Diet ◽  
Dependent Activity ◽  
Liver And Kidney ◽  
Phenylalanine Metabolism

SummaryThe effects of a diet of 85% casein on the activities of the phenylalanine hydroxylases of rat liver and kidney have been compared. Whereas only the tetrahydrobiopterin-dependent activity of rat hepatic phenylalanine hydroxylase is significantly stimulated, both the tetrahydrobiopterin-dependent and the dimethyltetrahydropterin- dependent activities of the renal enzyme are significantly decreased, after five days of feeding a casein diet. The animals fed a high protein diet for seven days have an increased rate of phenylalanine catabolism in vivo, which is also reflected in increased flux of label from phenylalanine into glucose. The regulation of phenylalanine metabolism, under these conditions, is discussed.

scholarly journals The regulation of phenylalanine hydroxylase in rat tissues in vivo. Substrate- and cortisol-induced elevations in phenylalanine hydroxylase activity

1976 ◽  
Vol 154 (3) ◽  
pp. 619-624 ◽  
Author(s):  
O Greengard ◽  
J A. Delvalle
Keyword(s):  
Phenylalanine Hydroxylase ◽  
Enzyme Concentration ◽  
Rat Tissues ◽  
Hydroxylase Activity ◽  
Adult Rats ◽  
No Inhibition ◽  
Hormonal Induction ◽  
Positive Regulators

Injections of phenylalanine increased a 2.5-fold in 9 h the hepatic phenylalanine hydroxylase activity of 6-day-old or adult rats that had been pretreated (24h earlier) with p-chlorophenylalanine; without such pretreatment, phenylalanine did not raise the enzyme concentration. This difference is paralleled by the much greater extent to which the injected phenylalanine accumulated in livers of the pretreated compared with the normal animals. The hormonal induction of hepatic phenylalanine hydroxylase activity obeyed different rules: an injection of cortisol was without effect on adult livers but caused a threefold rise in phenylalanine hydroxylase activity of immature ones, both without and after pretreatment with p-chlorophenylalanine. In the latter instance, the effects of cortisol, and of phenylalanine were additive. Actinomycin inhibited the cortisol- but not the substrate-induced increase of phenylalanine hydroxylase, whereas puromycin inhibited both. The results indicate that substrate and hormone, two potential positive regulators of the amount of the hepatic (but not the renal) phenylalanine hydroxylase, act independently by two different mechanisms. The negative effector, p-chlorophenylalanine, also appears to interact with the synthetic (or degradative) machinery rather than with the existing phenylalanine hydroxylase molecules: 24h were required in vivo for an 85% decrease to ensue, and no inhibition occurred in vitro when incubating the enzyme with p-chlorophenylalanine or with liver extracts from p-chlorophenylalanine-treated rats.

scholarly journals A tetrahidrobiopterin (BH4)-deficientia diagnosztikája és kezelése

2017 ◽  
Vol 158 (48) ◽  
pp. 1897-1902 ◽  
Author(s):  
János Bókay
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mental Retardation ◽  
Phenylalanine Hydroxylase ◽  
Clinical Course ◽  
Hydroxylase Activity ◽  
Mild Form ◽  
Tetrahydrobiopterin Deficiency ◽  
The Central Nervous System ◽  
Phenylalanine Metabolism

Abstract: Since the initial breaking discovery of Følling that the severe neurological consequences of phenylketonuria could be prevented by use of low phenylalanine (Phe) diet, it has been shortly recognised that defective phenylalanine metabolism may also arise from the deficiency of tetrahydrobiopterin (BH4) cofactor, required for phenylalanine-hydroxylase activity. Furthermore, as BH4 is in Phe metabolism, it is also a cofactor for the activities of tyrosine hydroxylase and tryptophane hydroxylase, enzymes required for the synthesis of catecholamines and serotonin neurotransmitters. Besides hyperphenylalaninemia in patients with tetrahydrobiopterin deficiencies, dopamine and serotonin deficiencies, with different disorders of the central nervous system also develop. Mild form of tetrahydrobiopterin deficiency is rare, most of the patients have severe neurological abnormalities including progressive mental retardation if not treated properly. Early diagnosis and treatment are essential and can improve the clinical course and prognosis. Orv Hetil. 2017; 158(48): 1897–1902.

scholarly journals The quantitative determination of phenylalanine hydroxylase in rat tissues. Its developmental formation in liver

1972 ◽  
Vol 127 (4) ◽  
pp. 669-674 ◽  
Author(s):  
Margaret M. McGee ◽  
Olga Greengard ◽  
W. Eugene Knox
Keyword(s):  
Phenylalanine Hydroxylase ◽  
Mitochondrial Fraction ◽  
Kinetic Properties ◽  
Rat Tissues ◽  
Hydroxylase Activity ◽  
Kidney Enzyme ◽  
Distribution Studies ◽  
Similar Kinetic ◽  
Reduced State

A sensitive method was developed for determining the phenylalanine hydroxylase activity of crude tissue preparations in the presence of optimum concentrations of the 6,7-dimethyl-5,6,7,8-tetrahydropterin cofactor (with ascorbate or dithiothreitol to maintain its reduced state) and substrate. Tissue distribution studies showed that, in addition to the liver, the kidney also contains significant phenylalanine hydroxylase activity, one-sixth (in rats) or half (in mice) as much per g as does the liver. The liver and the kidney enzyme have similar kinetic properties; both were located in the soluble phase and were inhibited by the nucleo-mitochondrial fraction. Phenylalanine hydroxylase, like most rat liver enzymes concerned with amino acid catabolism, develops late. On the 20th day of gestation, the liver (and the kidney) is devoid of phenylalanine hydroxylase and at birth contains 20% of the adult activity. During the second postnatal week of development, when the phenylalanine hydroxylase activity was about 40% of the adult value, an injection of cortisol doubled this value. Cortisol had no significant effect on phenylalanine hydroxylase in adult liver or on phenylalanine hydroxylase in kidney at any age.

scholarly journals Phenylalanine metabolism in isolated rat liver cells. Effects of glucagon and diabetes

1981 ◽  
Vol 198 (3) ◽  
pp. 655-660 ◽  
Author(s):  
F P A Carr ◽  
C I Pogson
Keyword(s):  
Metabolic Flux ◽  
Phenylalanine Hydroxylase ◽  
Experimental Diabetes ◽  
Hydroxylase Activity ◽  
Rat Liver Cells ◽  
Phenylalanine Metabolism ◽  
The Relationship ◽  
Substrate Concentrations ◽  
Isolated Liver

1. Methods are described for monitoring the metabolic flux through phenylalanine hydroxylase, the tyrosine catabolic pathway and phenylalanine: pyruvate transaminase in isolated liver cell incubations. 2. The relationship between hydroxylase flux and phenylalanine concentration is sigmoidal. 3. Glucagon increases hydroxylase activity at low, near-physiological, substrate concentrations only. The hormone does not affect the rate of formation of phenylpyruvate. 4. Experimental diabetes (for 10 days) increases phenylalanine catabolism, and this is further increased by glucagon. 5. These results are discussed in the light of the known mechanisms for control of phenylalanine hydroxylase activity in vitro.

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