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 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 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.

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 In vitro analysis of the origin and maintenance of O-2Aadult progenitor cells.

1992 ◽  
Vol 116 (1) ◽  
pp. 167-176 ◽  
Author(s):  
D Wren ◽  
G Wolswijk ◽  
M Noble
Keyword(s):  
Adult Life ◽  
Cell Types ◽  
Adult Rats ◽  
Optic Nerves ◽  
Limited Life ◽  
Old Rats ◽  
Vitro Analysis

We have been studying the differing characteristics of oligodendrocyte-type-2 astrocyte (O-2A) progenitors isolated from optic nerves of perinatal and adult rats. These two cell types display striking differences in their in vitro phenotypes. In addition, the O-2Aperinatal progenitor population appears to have a limited life-span in vivo, while O-2Aadult progenitors appear to be maintained throughout life. O-2Aperinatal progenitors seem to have largely disappeared from the optic nerve by 1 mo after birth, and are not detectable in cultures derived from optic nerves of adult rats. In contrast, O-2Aadult progenitors can first be isolated from optic nerves of 7-d-old rats and are still present in optic nerves of 1-yr-old rats. These observations raise two questions: (a) From what source do O-2Aadult progenitors originate; and (b) how is the O-2Aadult progenitor population maintained in the nerve throughout life? We now provide in vitro evidence indicating that O-2Aadult progenitors are derived directly from a subpopulation of O-2Aperinatal progenitors. We also provide evidence indicating that O-2Aadult progenitors are capable of prolonged self renewal in vitro. In addition, our data suggests that the in vitro generation of oligodendrocytes from O-2Aadult progenitors occurs primarily through asymmetric division and differentiation, in contrast with the self-extinguishing pattern of symmetric division and differentiation displayed by O-2Aperinatal progenitors in vitro. We suggest that O-2Aadult progenitors express at least some properties of stem cells and thus may be able to support the generation of both differentiated progeny cells as well as their own continued replenishment throughout adult life.

Relation between dietary-induced increase of intestinal lactase activity and lactose digestion and absorption in adult rats

1984 ◽  
Vol 247 (6) ◽  
pp. G729-G735
Author(s):  
J. Leichter ◽  
T. Goda ◽  
S. D. Bhandari ◽  
S. Bustamante ◽  
O. Koldovsky
Keyword(s):  
Glucose Absorption ◽  
Diet Group ◽  
Lactase Activity ◽  
Weight Changes ◽  
Adult Rats ◽  
High Starch ◽  
Old Rats ◽  
Starch Diet

To study the relation between dietary-induced increase of intestinal lactase activity and lactose absorption, 11-wk-old rats were fed either a high-starch (70 cal%), low-fat (7 cal%) diet or a low-starch (5 cal%), high-fat (73 cal%) diet for 7 days. Food intake and body weight changes were similar in the two dietary groups. In the first experiment, lactose absorption was studied in vivo after oral administration of 600 mg lactose (10% solution in water with added [3H]PEG) to rats fasted for 16 h. Groups of rats were killed at time 0 and at 1-h intervals for the next 3 h. Lactase activity and lactose absorption were significantly higher (P less than 0.01) in the high-starch group than in the low-starch group. In the subsequent experiment, 9-wk-old rats were fed the two isocaloric diets for 3 days. By use of the everted sac technique, we have demonstrated a significantly higher absorption of monosaccharides from lactose in the high-starch diet group; also, glucose transport was higher in the high-starch diet-fed animals. When Tris, an inhibitor of lactase, was added into the mucosal fluid, absorption of lactose was abolished and no effect was seen on glucose absorption (in vivo and in vitro). In both experiments, significant linear regression was established between lactase activity and lactose absorption. Our results thus show that the increase in lactase activity, induced by feeding a high-starch diet to adult rats, is accompanied by an increased capacity to hydrolyze lactose and absorb the constituent monosaccharides.

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.

PTH increases renal 25(OH)D3-1α-hydroxylase (CYP1α) mRNA but not renal 1,25(OH)2D3production in adult rats

2003 ◽  
Vol 284 (5) ◽  
pp. F1032-F1036 ◽  
Author(s):  
H. J. Armbrecht ◽  
M. A. Boltz ◽  
T. L. Hodam
Keyword(s):  
Ribonuclease Protection Assay ◽  
Mrna Levels ◽  
Fischer 344 Rats ◽  
Adult Rats ◽  
Dihydroxyvitamin D ◽  
Fischer 344 ◽  
Young Rats ◽  
Ribonuclease Protection ◽  
Cytochrome P 450

The capacity of parathyroid hormone (PTH) to stimulate renal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] production declines with age in the rat. The purpose of these studies was to determine whether this decline is due to a decreased capacity of PTH to increase the mRNA levels of CYP1α, the cytochrome P-450 component of the 25(OH)D3-1α-hydroxylase. Young (2 mo) and adult (12 mo) male Fischer 344 rats were parathyroidectomized (PTX). After 72 h, PTX rats were injected with PTH or vehicle at 24, 6, and 3 h before death, and renal CYP1α mRNA levels were measured by ribonuclease protection assay. In young rats, PTH markedly increased plasma 1,25(OH)2D3 and renal 1,25(OH)2D3 production. However, in adult rats, the response to PTH was less than 30% of that seen in young rats. Renal CYP1α mRNA levels, on the other hand, were increased over fivefold by PTH in both young and adult rats. In in vitro studies, PTH/forskolin increased CYP1α mRNA levels over twofold in renal slices from both young and adult PTX rats. These studies demonstrate that the decreased capacity of PTH to increase 1,25(OH)2D3 production in adult rats is not due to decreased induction of CYP1α mRNA.

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

Comparative age-related acute and chronic pulmonary oxygen tolerance in rats

1994 ◽  
Vol 77 (6) ◽  
pp. 2709-2719 ◽  
Author(s):  
S. Laudert ◽  
D. W. Thibeault ◽  
M. M. Rezaiekhaligh ◽  
S. M. Mabry ◽  
M. Huntrakoon
Keyword(s):  
Enzyme Activity ◽  
Heart Weight ◽  
Pulmonary Insufficiency ◽  
Initial Increase ◽  
Lung Water ◽  
Oxygen Tolerance ◽  
Young Rats ◽  
Arterial Blood ◽  
Age Related ◽  
Old Rats

Young rats are thought to be more tolerant to hyperoxia. We propose that this may not be proven and depends on how tolerance is defined. We assessed oxygen tolerance in Sprague-Dawley rats from birth to maturity by comparing survival, lung water, antioxidant enzyme activity, lung morphometrics, heart weight, and arterial blood gases in newborn and 27-, 44-, 48-, and 96-day-old rats exposed to 100% O2 or room air for 22 days. Some 96-day-old rats (rest group) received only 50% O2 between 48 and 72 h. Mortality after 5 days of O2 was 0% in newborn and 27-day-old rats and 27% in 44-day-old rats but was > 80% in 48- and 96-day-old rats. Between 5 and 22 days, the death rate was 100% in newborns, 25% in 27-day-old rats, and 0% in 44- to 96-day-old rats. Death occurred when lung water was > 84% except in newborns, which tolerated high lung water for the first 7 days. In chronically exposed 44- and 96-day-old rats, lung water returned to normal. Enzyme activity increased with O2 at all ages but did not relate to survival. In 96-day-old rats, the initial increase was suppressed on day 3. All chronically O2-exposed rats had minimal nonvascular parenchymal changes but developed right ventricular hypertrophy and increased alveolar ductal artery muscularization and lost alveolar capillaries. The most mature rats were least affected. In O2, there was pulmonary insufficiency the first 3 days, followed by recovery, and later hypercarbia and decreased arterial PO2. We conclude that young rats, 0–44 days old, are more O2 tolerant for 5 days. More mature animals, surviving 5 days, are more tolerant to chronic exposure.

AGE-RELATED CHANGES IN THE METABOLISM OF [3H]TESTOSTERONE IN VITRO BY THE EPIDIDYMIS OF THE IMMATURE RAT

1981 ◽  
Vol 91 (1) ◽  
pp. 43-51 ◽  
Author(s):  
R. G. FOLDESY ◽  
J. H. LEATHEM
Keyword(s):  
Adult Rats ◽  
Testosterone Metabolism ◽  
Pubertal Maturation ◽  
Immature Rat ◽  
Age Related ◽  
Rat Epididymis ◽  
Old Rats ◽  
Prepubertal Rats ◽  
Cauda Epididymidis

We examined the production in vitro of 5α-reduced metabolites from testosterone by the rat epididymis during pubertal maturation. Minced caput and cauda epididymides from 30-, 45-, and 55-day-old rats were incubated with [3H]testosterone for 2 h. Analysis of the radioactive metabolites revealed both similarities and differences in the metabolic patterns compared to those reported for adult rats. As in adults, 5α-dihydrotestosterone was the most abundant metabolite produced by both epididymal segments at all three ages, and it was formed in larger quantities in the caput epididymidis than in the cauda. However, [3H]testosterone metabolism by the epididymis of the immature rat was characterized by a lower formation of 5α-androstane-3α,17β-diol and higher production of 5α-androstane-3,17-dione than in adults. Production of these two metabolites by the caput region increased and decreased respectively, toward adult levels, with increasing age. In addition, the amount of [3H]testosterone metabolized was higher with tissues from prepubertal rats (30 days of age) than with those from rats 55 days of age. These data suggest that testosterone metabolism in the caput begins to change to that of the adult during the period of pubertal maturation but apparently not until later in the cauda epididymidis.

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