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

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.

1997 ◽  
pp. 701-708 ◽  
Author(s):  
A Blackburn ◽  
RA Dressendorfer ◽  
WF Blum ◽  
M Erhard ◽  
G Brem ◽  
...  

To study interactions between insulin-like growth factor-II (IGF-II) and growth hormone (GH) in vivo, we crossed hemizygous transgenic mice carrying phosphoenolpyruvate carboxykinase (PEPCK)-IGF-II fusion genes with hemizygous PEPCK-bovine GH (bGH) transgenic mice. Offspring harbouring both transgenes (IB), the IGF-II transgene (I) or the bGH transgene (B), and non-transgenic littermates (C) were obtained. Blood samples were taken before (end of week 12) and after (end of week 14) the mice had received a diet high in protein and low in carbohydrates to stimulate PEPCK promoter-controlled transgene expression. Mean serum GH concentrations of both B and IB mice corresponded to 900 ng/ml and increased more than twofold (P < 0.001) after 1 week of the high-protein diet. GH concentrations in controls and I mice were less than 20 ng/ml. Serum IGF-II concentrations in I and IB mice were three-to fourfold higher than those in C and B mice. Whereas IGF-II concentrations were not changed by the high-protein diet in the last two groups, serum IGF-II increased significantly in I (P < 0.001) and IB mice (P < 0.05). This increase was significantly (P < 0.05) less pronounced in IB than in C and I mice. Circulating IGF-I concentrations were about twofold (P < 0.001) higher in B and IB than in C and I mice, and showed a tendency to be lower in I than in C and in IB than in B mice when animals were maintained on the standard diet. The high-protein diet did not change circulating IGF-I concentrations in controls and B mice, but resulted in a significant reduction of serum IGF-I concentrations in I (P < 0.05) and IB mice (P < 0.001). Consequently, after PEPCK-IGF-II transgene expression was stimulated, serum IGF-I concentrations were significantly (P < 0.05) lower in I than in C and in IB than in B mice. Serum IGF-binding protein (IGFBP)-2 concentrations were significantly (P < 0.05) higher in I mice than in all other groups when mice were maintained on the standard diet, with a tendency to reduced IGFBP-2 concentrations in B mice. After the high-protein diet, serum IGFBP-2 concentrations did not change in C and I mice, but increased by two- to threefold in B and IB mice (P < 0.001). Serum IGFBP-3 concentrations tended to be greater in B and IB than in C and I mice, but these differences were mostly not significant. IGFBP-4 concentrations were significantly (P < 0.001) increased by GH overproduction in B and IB mice. Our data suggest that the reduction in circulating IGF-I concentrations by increased IGF-II is most probably due to the limited serum IGF binding capacity and the short half-life of free IGFs, rather than to a reduction in GH-dependent IGF-I production. Effects of GH overproduction on serum IGFBP-2 concentrations depend on dietary factors and may be both inhibitory and stimulatory.


1971 ◽  
Vol 49 (1) ◽  
pp. 108-118 ◽  
Author(s):  
B. Szepesi ◽  
R. A. Freedland

Enzymes associated with carbohydrate and amino acid metabolism as well as other liver constituents were studied in rats meal-fed, daily for 60 min, diets consisting of corn oil, salt, and vitamins plus 75% carbohydrate and 15% casein or a 90% casein diet. Relative liver size and the levels of liver glycogen and total and soluble liver protein were subject to periodic variation after the ingestion of a meal. They reached maximums about 6–12 h after the meal and then declined. In the rats fed the 90% casein diet the onset of increases was delayed after the first meal.The activity of glucose-6-phosphatase was increased by a fructose diet and the high-protein diet, but no periodicity was observed. The activities of fructose-1, 6-diphosphatase, dihydroxyacetone kinase, and malic enzyme were not subject to periodic variation, and these enzymes were not increased by the fructose or high-protein diets. Serine dehydrase activity was increased by the high-protein diet, but the question of periodicity cannot be resolved with the available data.The tyrosine–α-ketoglutarate transaminase activity in rats fed a 75% glucose – 15% casein diet was subject to periodic variation. Maximum activity occurred just before feeding, and minimum activity 12 h after feeding. In the rats fed the 90% casein diet the activity of the enzyme was considerably increased, and was already maximum 3 h after the meal. The activity then decreased to a relatively high minimum 12 h after the meal, at which time it began to increase again.The activities of pyruvate kinase, glucose-6-phosphate dehydrogenase, and phosphohexose isomerase were all subject to periodicity in the glucose-fed rats. In the rats fed the high-protein diet, there was a periodic response in activity of both pyruvate kinase and glucose-6-phosphate dehydrogenase after the first meal; but enzyme activity remained minimum after the second meal. Glucose-6-phosphate dehydrogenase and phosphohexose isomerase activities were increased after three meals of the fructose diet, and were higher than in glucose-fed rats even 24 h after a meal. Maximum activity of these three enzymes occurred 12 h after the meal. There was only small periodicity in the activity of glutamic–pyruvic transaminase. The activity of this enzyme was increased by the high-protein diet and also by the high-fructose diet, although the latter effect was only temporary. The possible importance of certain types of adaptations in meal-fed rats was discussed in connection with physiological requirements.


1968 ◽  
Vol 46 (10) ◽  
pp. 1253-1260 ◽  
Author(s):  
R. A. Freedland

Although many enzymes are increased by either a high-protein diet or cortisol adminstration, there was no evidence of a glucocorticoid requirement for the high-protein mediated increases. This was particularly noticeable for enzymes markedly increased by feeding a high-protein diet. Neither adrenalectomy nor hypophysectomy prevented the diet-mediated increases, although in certain instances the responses were decreased. Many enzymes which were unaffected or decreased in the intact rat by feeding a high-protein diet had markedly different responses after endocrine removal. There did not appear to be a general or simple pattern of these altered responses. Therefore predictions on possible activity changes could not be made, except for those enzymes normally increased by a high-protein diet on the basis of metabolic function or hormonal effects. Possible hormonal controls of these changes in enzyme activity are discussed.


2004 ◽  
Vol 16 (2) ◽  
pp. 190 ◽  
Author(s):  
D.K. Gardner ◽  
K.S. Stilley ◽  
M. Lane

Ammonium is known to adversely affect the development of mouse embryos in culture. Specifically, ammonium has been found to impair inner cell (ICM) mass formation, increase apoptosis, retard fetal development following embryo transfer and induce exencephaly. Significantly, high protein diets in cattle lead to reduced fecundity. This has been linked to elevated urea levels within fluid of the female tract. In this study we have determined the effects of a high protein diet for mice on the levels of ammonium within the female tract and the effects of such a diet on the development and viability of blastocysts developed in vivo. Outbred mice (CF1) were fed a diet of either 25% (high protein) or 14% (control) protein for 4 weeks. Females were superovulated and mated to males of the same strain. In 24 mice, oviduct fluid was collected at 22h post hCG. Ammonium in the oviduct fluid was then quantitated fluorometrically. From other animals, blastocysts were flushed 92h post hCG and analyzed. Blastocyst differentiation and apoptotic indices were determined. Values are mean±SEM. Data were analysed using Student’s t-test. The levels of ammonium in the oviduct were significantly higher (P&lt;0.01) in females fed the high protein diet (356±43μM) compared to the control (68±13μM) (n=12 in each group). Blastocysts (n=139) from females fed the high protein diet had significantly lower total (43.4±1.1; P&lt;0.05) and ICM cell numbers (12.7±0.4; P&lt;0.01), compared to the control group (46.8±0.9 and 15.4±0.4 respectively; n=124). Furthermore, blastocysts from animals fed a high protein diet had a significantly higher apoptotic index (8.7±1.4; P&lt;0.01) compared to the control group (2.0±0.5). These data show that consumption of a high protein diet results in the excess accumulation of ammonium in the fluid of the female reproductive tract of mice. These high levels of ammonium subsequently impair the formation of the fetal progenitor cells and increase cell death at the blastocyst stage. These data from in vivo-developed mouse blastocysts are similar to those for blastocysts developed in culture in the presence of 300μM ammonium. Therefore, it is not advisable to maintain mice on a high protein diet. These data have significant implications for animal breeding, and for patients attempting IVF treatment.


2008 ◽  
Vol 294 (3) ◽  
pp. R748-R755 ◽  
Author(s):  
M. Jourdan ◽  
L. Cynober ◽  
C. Moinard ◽  
M. C. Blanc ◽  
N. Neveux ◽  
...  

Splanchnic sequestration of amino acids (SSAA) is a process observed during aging that leads to decreased peripheral amino acid (AA) availability. The mechanisms underlying SSAA remain unknown. The aim of the present study was to determine whether a high-protein diet could increase nitrogen retention in aged rats by saturating SSAA and whether SSAA could be explained by dysregulation of hepatic nitrogen metabolism. Adult and aged male Sprague-Dawley rats were housed in individual metabolic cages and fed a normal-protein (17% protein) or high-protein diet (27%) for 2 wk. Nitrogen balance (NB) was calculated daily. On day 14, livers were isolated and perfused for 90 min to study AA and urea fluxes. NB was lower in aged rats fed a normal-protein diet than in adults, but a high-protein diet restored NB to adult levels. Isolated perfused livers from aged rats showed decreased urea production and arginine uptake, together with a release of alanine (vs. uptake in adult rats) and a hepatic accumulation of alanine. The in vivo data suggest that SSAA is a saturable process that responds to an increase in dietary protein content. The hepatic metabolism of AA in aged rats is greatly modified, and urea production decreases. This result refutes the hypothesis that SSAA is associated with an increase in AA disposal via urea production.


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