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.

scholarly journals The effect of experimental diabetes on phenylalanine metabolism in isolated liver cells

1985 ◽  
Vol 227 (1) ◽  
pp. 169-175 ◽  
Author(s):  
M A Santana ◽  
M J Fisher ◽  
A J Bate ◽  
C I Pogson
Keyword(s):  
Enzyme Activity ◽  
Hormonal Regulation ◽  
Metabolic Flux ◽  
Phenylalanine Hydroxylase ◽  
Experimental Diabetes ◽  
Liver Cells ◽  
Enzyme Protein ◽  
Isolated Liver Cells ◽  
Phenylalanine Metabolism ◽  
Isolated Liver

Chronic (10-day) diabetes was associated with increased metabolic flux through phenylalanine hydroxylase in isolated liver cells. This flux was stimulated by 0.1 microM-glucagon, but not by 10 microM-noradrenaline; 0.1 microM-insulin affected neither basal nor glucagon-stimulated flux. The increased rate of phenylalanine hydroxylation in diabetes was accompanied by parallel increases in enzyme activity (as measured with artificial cofactor) and immunoreactive-enzyme-protein content. In contrast with total protein synthesis, which decreased, phenylalanine hydroxylase synthesis persisted at the control rate in cells from diabetic animals. These findings are discussed in relation to the hormonal regulation of the hydroxylase and the known metabolic consequences of chronic diabetes.

Atypical Phenylketonuria With Normal Phenylalanine Hydroxylase and Dihydropteridine Reductase Activity in Vitro

PEDIATRICS ◽  
1977 ◽  
Vol 59 (5) ◽  
pp. 757-761
Author(s):  
Klaus Bartholomé ◽  
Dennis J. Byrd ◽  
Seymour Kaufman ◽  
Sheldon Milstien
Keyword(s):  
Phenylalanine Hydroxylase ◽  
Reductase Activity ◽  
Neurological Symptoms ◽  
Molecular Defect ◽  
Restricted Diet ◽  
Hydroxylase Activity ◽  
Normal Range ◽  
Phenylalanine Metabolism ◽  
Atypical Phenylketonuria

A child with phenylketonuria had normal phenylalanine hydroxylase activity in vitro. In addition, all known components of the phenylalanine hydroxylating system were within the normal range. Despite early treatment with a phenylalanine-restricted diet, the patient developed severe neurological symptoms. Although the primary molecular defect in this child is not known, there are indications that the defect lead to disturbances in phenylalanine metabolism and in the biosynthesis of L-dopa and L-5-hydroxytryptophan. The administration of these two precursors of neurotransmitters brought about a notable improvement in the patient's neurological symptoms.

scholarly journals Liver phenylalanine hydroxylase activity in relation to blood concentrations of tyrosine and phenylalanine in the rat

1972 ◽  
Vol 127 (4) ◽  
pp. 675-680 ◽  
Author(s):  
Margaret M. McGee ◽  
Olga Greengard ◽  
W. Eugene Knox
Keyword(s):  
Phenylalanine Hydroxylase ◽  
Quantitative Relationship ◽  
Initial Increase ◽  
Hydroxylase Activity ◽  
Adult Rats ◽  
Blood Concentrations ◽  
Young Rats ◽  
Old Rats ◽  
Phenylalanine Metabolism

The plasma concentration of phenylalanine and tyrosine decreases in normal rats during the first few postnatal days; subsequently, the concentration of phenylalanine remains more or less constant, whereas that of tyrosine exhibits a high peak on day 13. The basal concentrations of the two amino acids were not altered by injections of thyroxine or cortisol, except in 13-day-old rats, when an injection of cortisol decreased the concentration of tyrosine. In young rats (13–15 days old), treatment with cortisol increased the activity of phenylalanine hydroxylase in the liver (measured in vitro) and accelerated the metabolism of administered phenylalanine: the rate constant of the disappearance of phenylalanine from plasma and the initial increase in tyrosine in plasma correlated quantitatively with the activity of phenylalanine hydroxylase in the liver. In adult rats, the inhibition of this enzyme (attested by assay in vitro) by p-chlorophenylalanine resulted in a proportionate decrease in tyrosine formation from an injection of phenylalanine. However, the quantitative relationship between liver phenylalanine hydroxylase activity and phenylalanine metabolism within the group of young rats was different from that observed among adult rats.

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 Endocytosis of formaldehyde-treated serum albumin via scavenger pathway in liver endothelial cells

1984 ◽  
Vol 218 (1) ◽  
pp. 81-86 ◽  
Author(s):  
R Blomhoff ◽  
W Eskild ◽  
T Berg
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Surface Culture ◽  
Rat Liver Cells ◽  
Liver Endothelial Cells ◽  
Isolated Liver

Denatured or modified proteins (including albumin and low-density lipoprotein) are catabolized in vitro via scavenger receptors. We have studied the distribution of formaldehyde-denatured albumin in rat liver cells after intravenous injection of tracer doses of the protein. At 12 min after injection, most of the formaldehyde-denatured albumin (about 70% of the injected dose) was recovered in liver endothelial cells. Furthermore, isolated liver endothelial cells in suspension and in surface culture took up formaldehyde-denatured albumin by receptor-mediated endocytosis. Our data indicate that the scavenger receptor in liver is mainly located on the endothelial cells. Implications for the catabolism of low-density lipoproteins are discussed.

Molecular genetics and impact of residual in vitro phenylalanine hydroxylase activity on tetrahydrobiopterin responsiveness in Turkish PKU population

2011 ◽  
Vol 102 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Steven F. Dobrowolski ◽  
Caroline Heintz ◽  
Trent Miller ◽  
Clinton Ellingson ◽  
Clifford Ellingson ◽  
...  
Keyword(s):  
Molecular Genetics ◽  
Phenylalanine Hydroxylase ◽  
Hydroxylase Activity

A study of the in vitro clinical interaction between lidocaine and premedications using rat liver microsomes

2002 ◽  
Vol 21 (8) ◽  
pp. 453-456 ◽  
Author(s):  
A Nagashima ◽  
E Tanaka ◽  
S Inomata ◽  
S Misawa
Keyword(s):  
Liver Microsomes ◽  
Competitive Inhibitor ◽  
Rat Liver Microsomes ◽  
Dependent Manner ◽  
Potential Importance ◽  
Concentration Dependent Manner ◽  
Hepatic Microsomes ◽  
The Relationship ◽  
Substrate Concentrations

In this study, we have investigated the relationship between lidocaine metabolism and premedication, i.e., psychotropic and anti-anxiety agents (diazepam, midazolam), hypnotics (pentobarbital, thiamylal), depolarizing muscular relaxants (vecuronium, pancuronium and suxamethonium), an active anti-hypertensive (clonidine) and an H2 receptor antagonist (cimetidine) using rat hepatic microsomes in vitro. Lidocaine metabolism was noncompetitively inhibited by midazolam (Ki=29.0 mM). Thilamylal was a moderate competitive inhibitor of lidocaine metabolism (Ki=77.8 mM). Pentobarbital, diazepam and cimetidine weakly inhibited lidocaine metabolism formation in a concentration-dependent manner at high substrate concentrations. On the other hand, vecuronium, pancuronium, suxamethonium and clonidine did not inhibit lidocaine metabolism over the therapeutic range. These results show that the interaction between lidocaine and midazolam and thiamylal, catalyzed by a similar cytochrome P450, is of potential importance in toxicological and clinical studies.

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.

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