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PubMed1983

Quantitative analysis of flux along the gluconeogenic, glycolytic and pentose phosphate pathways under reducing conditions in hepatocytes isolated from fed rats.

Hepatocytes were isolated from the livers of fed rats and incubated with a mixture of glucose (10 mM), ribose (1 mM), mannose (4 mM), glycerol (3 mM), acetate (1.25 mM), and ethanol (5 mM) with one substrate labelled with 14C in any given incubation. Incorporation of label into CO2, glucose, glycogen, lipid glycerol and fatty acids, acetate and C-1 of glucose was measured at 20 and 40 min after the start of the incubation. The data (about 48 measurements for each interval) were used in conjunction with a single-compartment model of the reactions of the gluconeogenic, glycolytic and pentose phosphate pathways and a simplified model of the relevant mitochondrial reactions. An improved method of computer analysis of the equations describing the flow of label through each carbon atom of each metabolite under steady-state conditions was used to compute values for the 34 independent flux parameters in this model. A good fit to the data was obtained, thereby permitting good estimates of most of the fluxes in the pathways under consideration. The data show that: net flux above the level of the triose phosphates is gluconeogenic; label in the hexose phosphates is fully equilibrated by the second 20 min interval; the triose phosphate isomerase step does not equilibrate label between the triose phosphates; substrate cycles are operating at the glucose-glucose 6-phosphate, fructose 6-phosphate-fructose 1,6-bisphosphate and phosphoenolpyruvate-pyruvate-oxaloacetate cycles; and, although net flux through the enzymes catalysing the non-oxidative steps of the pentose phosphate pathway is small, bidirectional fluxes are large.

Acetates↗
PubMed1983

The control of adenosine concentration in polymorphonuclear leucocytes, cultured heart cells and isolated perfused heart from the rat.

Rat polymorphonuclear leucocytes or neonatal-rat heart cells in culture were treated with 2'-deoxycoformycin and 5-iodotubercidin at concentrations that inhibited adenosine deaminase (EC 3.5.4.4) and adenosine kinase (EC 2.7.1.20) inside the intact cells, and the rate of adenosine accumulation was determined. The basal rate of adenosine formation was 2% (polymorphonuclear leucocytes) or 9% (heart cells) of the maximal activity of adenosine kinase also measured in intact cells. Greatly increased rates of adenosine formation were observed during adenine nucleotide catabolism. This condition also led to a decrease in adenosine kinase activity. When isolated rat hearts were perfused with 5-iodotubercidin alone at a concentration which inhibited adenosine kinase, no increase in tissue or perfusate adenosine or inosine concentration was observed. However, perfusion with hypoxic buffer or infusion of adenosine into the coronary circulation at a rate (20 nmol/min) equivalent to 40% of the activity of adenosine kinase caused large increases in effluent perfusate adenosine and inosine concentrations. These data argue unanimously against the existence of a substrate cycle controlling adenosine concentration. They suggest instead that an increase in the rate of adenosine formation is the principal cause of elevations in adenosine concentration during ATP catabolism.

Adenosine↗
PubMed1984

The influence of renal function on lactate and glucose metabolism.

The relationship of lactate metabolism to renal function was studied in the isolated perfused rat kidney. A new radioisotopic method has been developed that enables the simultaneous measurement of lactate production and consumption in the presence of physiological concentrations of both lactate and glucose. In kidneys from fed rats, when glucose was absent, lactate production was only 12 mumol/h per g dry wt, and in kidneys from starved rats there was no lactate production, indicating that neither the phosphoenolpyruvate/pyruvate substrate cycle nor other analogous cycles for the recycling of lactate carbon are operating in the intact kidney cortex. Lactate production from glucose occurred at a high rate, at the same time as lactate consumption, demonstrating that lactate recycling between renal cortex and medulla can occur in the intact kidney. Lactate production from glucose correlated with glomerular filtration rate (P less than 0.001), urine flow rate (P less than 0.01) and sodium reabsorption (P less than 0.05). There was significant basal lactate production at zero glomerular filtration rate. Lactate consumption was not correlated with any renal function. When Na+ reabsorption was inhibited with the diuretic frusemide, or when filtration was entirely prevented (the 'non'-filtering kidney'), lactate production was decreased by 39% and 50% respectively. Basal lactate production determined in this way was the same as that calculated above by linear regression. Prevention of filtration, but not the addition of frusemide, significantly inhibited lactate consumption. It is concluded that glycolysis is required for medullary Na+ transport, and that some different transport function(s) require lactate oxidation.

Animals↗
PubMed1988

Tissue-specific effects of rapid tumour growth on lipid metabolism in the rat during lactation and on litter removal.

1. The effect of tumour burden on lipid metabolism was examined in virgin, lactating and litter-removed rats. 2. No differences in food intake or plasma insulin concentrations were observed between control animals and those bearing the Walker-256 carcinoma (3-5% of body wt.) in any group studied. 3. In virgin tumour-bearing animals, there was a significant increase in liver mass, blood glucose and lactate, and plasma triacylglycerol; the rate of oxidation of oral [14C]lipid to 14CO2 was diminished, and parametrial white adipose tissue accumulated less [14C]lipid compared with pair-fed controls. 4. These findings were accompanied by increased accumulation of lipid in plasma and decreased white-adipose-tissue lipoprotein lipase activity. 5. In lactating animals, tumour burden had little effect on the accompanying hyperphagia or on pup weight gain; tissue lipogenesis was unaffected, as was tissue [14C]lipid accumulation, plasma [triacylglycerol] and white-adipose-tissue and mammary-gland lipoprotein lipase activity. 6. On removal (24 h) of the litter, the presence of the tumour resulted in decreased rates of lipogenesis in the carcass, liver and white and brown adipose tissue, decreased [14C]lipid accumulation in white adipose tissue, but increased accumulation in plasma and liver, increased plasma [triacylglycerol] and decreased lipoprotein lipase activity in white adipose tissue. 7. The rate of triacylglycerol/fatty acid substrate cycling was significantly decreased in white adipose tissue of virgin and litter-removed rats bearing the tumour, but not in lactating animals. 8. These results demonstrate no functional impairment of lactation, despite the presence of tumour, and the relative resistance of the lactating mammary gland to the disturbance of lipid metabolism that occurs in white adipose tissue of non-lactating rats with tumour burden.

Animals↗
PubMed1989

Evidence that the production of acetate in rat hepatocytes is a predominantly cytoplasmic process.

By using [1-14C]butyrate, the fluxes of butyrate to acetate and fatty acids were measured in rat hepatocytes. Both fluxes were inhibited to a similar extent by (-)-hydroxycitrate, with no significant effect on butyrate uptake. These results indicate that acetate formation takes place in the cytoplasm, presumably via ATP-stimulated acetyl-CoA hydrolase. Since acetate formation occurred despite a net uptake of acetate, the results are also consistent with the operation of a substrate cycle between acetate and acetyl-CoA, recently proposed by other workers, and suggest that this cycle is cytoplasmic.

Acetates↗
PubMed1991

Algorithms for the derivation of Flux and Concentration Control Coefficients.

A computer program is described that derives the Flux and Concentration Control Coefficients for linear and branched metabolic pathways. The program prompts the user to enter a concise description of the metabolic pathway. From this description, the program constructs the appropriate equations in matrix form. The algorithm employed to obtain the symbolic determinants is described, and this algorithm also provides a convenient method for manual derivation of the Control Coefficients. The computer-based method will accommodate unlimited feed-forward and feed-backward loops and a maximum of two branches from each metabolite on the main pathway. The utility of the method is illustrated with a linear path with feed-forward and feed-backward loops, and with a substrate cycle as an example of a path with two branches.

Algorithms↗
PubMed1993

Mechanisms of elevation of adenosine levels in anoxic hepatocytes.

Previous work has shown that normoxic isolated rat hepatocytes continuously produce adenosine from AMP and that the nucleoside is not catabolized further but immediately rephosphorylated by adenosine kinase [Bontemps, Van den Berghe and Hers (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 2829-2833]. We now report the effect of anoxia on adenosine production and on the AMP/adenosine substrate cycle. In cell suspensions incubated in O2/CO2, the adenosine concentration was about 0.4 microM. It increased 30-fold in cells incubated in N2/CO2 or with 5 mM KCN, and 20-fold in cells incubated with 2 mM amytal. Adenosine production, measured in hepatocytes in which adenosine kinase and adenosine deaminase were inhibited by 5-iodotubercidin and deoxycoformycin respectively, was about 18 nmol/min per g of cells in normoxia; it increased about 2-fold in anoxia, although AMP increased 8-16-fold in this condition. From studies with inhibitors of membrane 5'-nucleotidase and of S-adenosylhomocysteine hydrolase, it was deduced that adenosine is produced by the latter enzyme and by cytosolic 5'-nucleotidase in normoxia, and by cytosolic and membrane 5'-nucleotidases in anoxia. Unlike in normoxic hepatocytes, inhibition of adenosine kinase by 5-iodotubercidin neither elevated the adenosine concentration nor enhanced total purine release from adenine nucleotides in cells treated with N2/CO2 or KCN; it had only a slight effect in cells treated with amytal. This indicates that recycling of adenosine is suppressed or profoundly inhibited in anoxia. The rate of accumulation of adenosine in anoxia was several-fold lower than the rate of its rephosphorylation upon reoxygenation. It is concluded that the elevation of adenosine in anoxic hepatocytes is much more dependent on decreased recycling of adenosine by adenosine kinase than on increased production by dephosphorylation of AMP.

5'-Nucleotidase↗
PubMed1991

Glucose utilization by sheep embryos derived in vivo and in vitro.

Embryos were collected from superovulated donors at various intervals from onset of oestrus, ranging from Day 1.5 to Day 6. In addition, blastocysts obtained from the culture of 1-cell embryos collected in vivo or of oocytes matured and fertilized in vitro were used to assess the effects of in vitro manipulation and culture on glucose utilization. Glycolytic activity was determined by the conversion of [5-3H]glucose to 3H2O, and oxidation of glucose was determined by the conversion of [U-14C]glucose to 14CO2. Glucose utilization increases significantly from the 8-cell stage and during compaction and blastulation. Glucose oxidation was at a relatively low level (5-12% of total utilization) compared with glycolysis. No difference was observed between the glycolytic activity of blastocysts derived from in vivo or in vitro sources. However, glucose oxidation was lower (P less than 0.05) in blastocysts derived from the culture of 1-cell embryos or from oocytes matured and fertilized in vitro. Exogenous tricarboxylic acid cycle substrates (i.e. pyruvate and lactate supplied in the medium) affected the level of glucose oxidation.

2,4-Dinitrophenol↗
PubMed1995

Synthesis and metabolism of bis-diphosphoinositol tetrakisphosphate in vitro and in vivo.

The pathway of synthesis and metabolism of bis-diphosphoinositol tetrakisphosphate (PP-InsP4-PP) was elucidated by high performance liquid chromatography using newly available 3H- and 32P-labeled substrates. Metabolites were also identified by using two purified phosphatases in a structurally diagnostic manner: tobacco "pyrophosphatase" (Shinshi, H., Miwa, M., Kato, K., Noguchi, M. Matsushima, T., and Sugimura, T. (1976) Biochemistry 15, 2185-2190) and rat hepatic multiple inositol polyphosphate phosphatase (MIPP; Craxton, A., Ali, N., and Shears, S. B. (1995) Biochem. J. 305, 491-498). The demonstration that diphosphoinositol polyphosphates were hydrolyzed by MIPP provides new information on its substrate specificity, although MIPP did not metabolize significant amounts of these polyphosphates in either rat liver homogenates or intact AR4-2J cells. In liver homogenates, inositol hexakisphosphate (InsP6) was phosphorylated first to a diphosphoinositol pentakisphosphate (PP-InsP5) and then to PP-InsP4-PP. These kinase reactions were reversed by phosphatases, establishing two coupled substrate cycles. The two dephosphorylations were probably performed by distinct phosphatases that were distinguished by their separate positional specificities, and their different sensitivities to inhibition by F- (IC50 values of 0.03 mM and 1.4 mM against PP-InsP5 and PP-InsP4-PP, respectively). In [3H]inositol-labeled AR4-2J cells, the steady-state levels of PP-[3H]InsP5 and PP-[3H]InsP4-PP were, respectively, 2-3 and 0.6% of the level of [3H]InsP6. The ongoing turnover of these polyphosphates was revealed by treatment of cells with 0.8 mM NaF for 40 min, which reduced levels of [3H]InsP6 by 50%, increased the levels of PP-[3H]InsP5 16-fold, and increased levels of PP-[3H]InsP4-PP 5-fold. A large increase in levels of PP-[3H]InsP5 also occurred in cells treated with 10 mM NaF, but then no significant change to levels of PP-[3H]InsP4-PP were observed; there may be important differences in the control of the turnover of these two compounds.

Animals↗
PubMed2006

UCP1-independent thermogenesis in white adipose tissue of cold-acclimated Ucp1-/- mice.

Apart from UCP1-based nonshivering thermogenesis in brown adipocytes, the identity of thermogenic mechanisms that can be activated to reduce a positive energy balance is largely unknown. To identify potentially useful mechanisms, we have analyzed physiological and molecular mechanisms that enable mice, genetically deficient in UCP1 and sensitive to acute exposure to the cold at 4 degrees C, to adapt to long term exposure at 4 degrees C. UCP1-deficient mice that can adapt to the cold have increased oxygen consumption and show increased oxidation of both fat and glucose as indicated from serum metabolite levels and liver glycogen content. Enhanced energy metabolism in inguinal fat was also indicated by increased oxygen consumption and fat oxidation in tissue suspensions and increased AMP kinase activity in dissected tissues. Analysis of gene expression in skeletal muscle showed surprisingly little change between cold-adapted Ucp1+/+ and Ucp1-/- mice, whereas in inguinal fat a robust induction occurred for type 2 deiodinase, sarcoendoplasmic reticulum Ca2+-ATPase, mitochondrial glycerol 3-phosphate dehydrogenase, PGC1alpha, CoxII, and mitochondrial DNA content. Western blot analysis showed an induction of total phospholamban and its phosphorylated form in inguinal fat and other white fat depots, but no induction was apparent in muscle. We conclude that alternative thermogenic mechanisms, based in part upon the enhanced capacity for ion and substrate cycling associated with brown adipocytes in white fat depots, are induced in UCP1-deficient mice by gradual cold adaptation.

Adenosine Triphosphatases↗
PubMed2002

Nutritional regulation of glucose-6-phosphatase gene expression in liver of the gilthead sea bream (Sparus aurata).

To examine the role of glucose-6-phosphatase (G6Pase) in glucose homeostasis in the diabetes-like experimental model of carnivorous fish, we analysed postprandial variations and the effect of starvation, ration size and diet composition on the regulation of G6Pase expression at the enzyme activity and mRNA level in the liver of gilthead sea bream (Sparus aurata). G6Pase expression increased in long-term starved or energy-restricted fish. In contrast to data reported for other fish species, short-term regulation of G6Pase expression was found in regularly fed S. aurata. G6Pase mRNA levels were lowest between 4 and 15 h after food intake, whereas minimal enzyme activity was observed 10-15 h postprandially. Alterations of plasma glucose levels affect G6Pase in mammals. However, the carbohydrate content of the diet did not affect hepatic expression of G6Pase in S. aurata, suggesting that a different molecular mechanism is involved in the control of G6Pase expression in fish. Although G6Pase was unaffected, high-carbohydrate low-protein diets increased glucokinase (GK) expression and thus allowed a metabolic adaptation favouring glycolysis over gluconeogenesis. Interestingly, only the nutritional conditions that promoted variations in the blood glucose levels resulted in changes in the hepatic expression of G6Pase. These findings indicate a concerted regulation of G6Pase and GK expression and suggest that the direction and rate of the glucose-glucose-6-phosphate substrate cycle flux is finely regulated in the liver of S. aurata, challenging the role attributed to deficient regulation of G6Pase or GK expression in the low ability of carnivorous fish to metabolize glucose.

Animals↗
PubMed1986

Orotic acid, arginine, and hepatotoxicity.

This communication presents evidence from the literature and recent experiments that describe circumstances wherein arginine may be a conditional dietary essential. Previous work has established that the synthesis of orotic acid (OA), the first pyrimidine formed in the de novo pathway of nucleic acid synthesis, becomes elevated whenever the ammonia load exceeds the capacity of the urea cycle. Under these circumstances, the common intermediate, carbamyl phosphate, leaks from the mitochondria and induces OA synthesis in the cytoplasm. This leads to increased OA excretion in the urine as pyrimidine synthesis escapes feedback control. A deficiency of urea cycle substrates such as arginine, and administration of certain drugs, ammonium salts, urease, or excess amino acids raises orotic acid excretion. Our recent experiments in rats show that OA excretion is also elevated after partial hepatectomy following galactosamine administration, exposure to carbon tetrachloride, or feeding 36% of calories as ethanol. The elevation in OA excretion was suppressed by dietary supplementation with arginine, implying that arginine is conditionally essential. Adult human male alcoholics showed elevated urinary orotic acid-to-creatinine ratios early after drinking episodes, which declined with time following abstinence. Such evidence shows that well studied hepatotoxins and surgical liver injury affect pathways of ammonia metabolism and suggests that urinary orotic acid can be an indicator of hepatotoxicity and increased needs for arginine. Arginine-deficient diets and alcohol feeding both enhance fatty deposition in the liver, which can be worsened by high fat intakes in rats. Alcoholism, various other diseases, and fasting and realimentation change orotic acid excretion. Such responses will have to be taken into account in establishing "normal values" for OA excretion.

Adult↗
PubMed1961

Fine structural alterations in cell particles during chemical carcinogenesis. III. Selective action of hepatic carcinogens other than 3'-methyl-4-dimethylaminoazobenzene on different types of mitochondrial swelling. Effect of stimulated liver growth.

The previous studies on the correlation between tumor incidence and changes in microsomal and mitochondrial swelling during feeding of 3'-methyl-4-dimethylaminoazobenzene to rats have been extended to other hepatic carcinogens. Administration of 4'-fluoro-4-dimethylaminoazobenzene, 4'-ethyl-2-methyl-4-dimethylaminoazobenzene, 2-acetylam-inofluorene, ethionine, and tannic acid were found to produce drastic alterations of the swelling of rat liver mitochondria. In contrast to these compounds, feeding of the non-carcinogenic azobenzene and 4-diethylaminoazobenzene produced only small changes in swelling. Significant modification in the over-all pattern of the swelling curve was observed when the usual concentration of 3'-methyl-4-dimethylaminoazobenzene was reduced, but not when the riboflavin level in the diet was increased tenfold. Feeding of high levels of this dye to the guinea pig did not affect mitochondrial swelling which is consistent with the resistance of this species to azo-dye carcinogenesis. Hypophysectomy provides protection against the alterations, produced by feeding 3'-methyl-4-dimethylaminoazobenzene, in the characteristics of thyroxine- or mercuric chloride-induced mitochondrial swelling. Studies with citric cycle substrates on mitochondrial swelling suggest block of the glutamate right harpoon over left harpoon alpha-keto-glutarate pathway after feeding 3'-methyl-4-dimethylaminoazobenzene for 4 weeks. There is a considerable, but reversible, reduction of certain types of mitochondrial swelling in two situations associated with rapid liver growth: after partial hepatectomy and after intraperitoneal injection of 20-methylcholanthrene. Naphthacene, however, which also stimulates rapid liver growth, does not affect mitochondrial swelling.

Animals↗
PubMed1974

Ultrastructure, steroidogenic potential, and energy metabolism of the Snell adrenocortical carcinoma 494. A comparison with normal adrenocortical tissue.

Electron microscope studies were carried out with the adrenocortical carcinoma 494 and normal adrenal cortex tissue. The mitochondria of the tumor cells showed marked differences when compared with mitochondria from fasciculata cells of the normal adrenal cortex. These differences were primarily related to mitochondrial number and crista structure. Corticosterone production in isolated tumor cells was extremely low and neither ACTH nor dibutyryl cyclic AMP had any stimulatory effect. Normal adrenal cells showed at least a tenfold increase under identical conditions. In the presence of corticosteroid precursors the amount of corticosterone produced by the tumor cells was much less than that produced by normal cells. The results indicate a reduced capacity for 11beta-hydroxylation in the tumor mitochondria and a possible reduced capacity for biosynthetic steps before the 11beta-hydroxylation reaction. Glycolysis in isolated tumor cells was also lower than in normal cells. Isolated tumor mitochondria oxidized succinate normally with a good degree of coupling with phosphorylation. However, unlike normal adrenal mitochondria, the tumor mitochondria showed little or no oxygen uptake with other Krebs cycle substrates. These data suggest that the tumor mitochondria may be lacking in the flavoprotein dehydrogenases responsible for the oxidation of NADH and NADPH, although other components of the respiratory chain may be intact.

Adrenal Cortex↗
PubMed2005

Protein synthesis by rice coleoptiles during prolonged anoxia: implications for glycolysis, growth and energy utilization.

BACKGROUND AND AIMS: Anoxia-tolerant plant tissues synthesize a number of proteins during anoxia, in addition to the 'classical anaerobic proteins' involved in glycolysis and fermentation. The present study used a model system of rice coleoptile tips to elucidate patterns of protein synthesis in this anoxia-tolerant plant tissue. METHODS: Coleoptile tips 7-11 mm long were excised from intact seedlings exposed to anoxia, or excised from hypoxically pre-treated seedlings and then exposed to anoxia for 72 h. Total proteins or 35S-labelled proteins were extracted, separated using two-dimensional isoelectric focusing/SDS-polyacrylamide gel electrophoresis and analysed using mass spectrometry. KEY RESULTS: The coleoptile tips excised after intact seedlings had been exposed to anoxia for 72 h had a similar proteome to tips that were first excised and then exposed to anoxia. After 72 h anoxia, Bowman-Birk trypsin inhibitors and a glycine-rich RNA-binding protein decreased in abundance, whereas a nucleoside diphosphate kinase and several proteins with unknown functions were strongly enhanced. Using [35S]methionine as label, proteins synthesized at high levels in anoxia, and also in aeration, included a nucleoside diphosphate kinase, a glycine-rich RNA-binding protein, a putative elicitor-inducible protein and a putative actin-depolymerizing factor. Proteins synthesized predominately in anoxia included a pyruvate orthophosphate dikinase (PPDK), alcohol dehydrogenase 1 and 2, fructose 1,6-bisphosphate aldolase and a protein of unknown function. CONCLUSION: The induction of PPDK in anoxic rice coleoptiles might, in combination with pyruvate kinase (PK), enable operation of a 'substrate cycle' producing PPi from ATP. Production of PPi would (a) direct energy to crucial transport processes across the tonoplast (i.e. the H+-PPiase); (b) be required for sucrose hydrolysis via sucrose synthase; and (c) enable acceleration of glycolysis, via pyrophosphate:fructose 6-phosphate 1-phosphotransferase (PFP) acting in parallel with phosphofructokinase (PFK), thus enhancing ATP production in anoxic rice coleoptiles; ATP production would need to be increased if there was a substantial requirement for PPi.

Energy Metabolism↗
PubMed1991

The Michaelis-Menten equation: computing substrate concentration as a function of time without restrictions on the initial conditions.

We describe a novel algorithm for enzyme kinetics following the Michaelis-Menten equation, with the particular aim of computing the substrate concentration as a function of time without restrictions on the initial conditions. This algorithm, named 'tangent exponential' was demonstrated to converge for all initial conditions when the initial substrate concentration is positive. When the data are close to the solution, a quadratic convergence was demonstrated.

Algorithms↗
PubMed1987

Simulation of the metabolism of absorbed energy-yielding nutrients in young sheep: efficiency of utilization of acetate.

A previously described mathematical model that simulates the metabolism of absorbed nutrients was used to examine factors influencing the efficiency of utilization of acetate in a sheep weighing 25 kg. A significant component of the model was a function representing substrate cycles that degraded ATP when its concentration reached twice initial levels. Acetate utilization was simulated when up to 2 g mol/d were added to four diets (representing forages and concentrates) that supplied varying proportions of absorbed volatile fatty acids, glucose and protein. The basal diets provided either 4.375 (near energy balance) or 8.75 MJ/d absorbed energy. The predicted net efficiency of utilization (kf) of the energy in added acetate was high (0.58-0.70) for all combinations of absorbed nutrients at the low level of energy absorption, whereas at the higher level, it ranged from 0.16 (forage) to 0.49 (high protein concentrate). Low kf values were always associated with a considerable flux of ATP through the degradation pathway. The increase in ATP concentration that caused this pathway to operate was linked to an inhibition in the utilization of acetyl-CoA for fatty acid synthesis and an increase in its oxidation. The simulated addition of exogenous NADPH or its precursors (particularly glucose and propionate) to these diets repartitioned acetyl-CoA flux towards fatty acid synthesis instead of oxidation, decreased the flux of ATP through the degradation pathway and increased the kf of added acetate. Although a negative relationship was predicted between kf of added acetate and NADPH production for diets with increasing protein content, kf still depended on ATP flux through the degradation pathway. Addition of glucose to the high protein diets decreased this flux by decreasing acetyl-CoA oxidation and increasing fatty acid synthesis. The predictions suggest that the efficiency of acetate utilization in ruminants may be influenced by NADPH availability when a considerable amount of absorbed energy is derived from acetate. Increased absorption of glucose or propionate enhanced NADPH production, but the major effect on acetate utilization of increasing dietary protein was not through NADPH production.

Absorption↗
PubMed1987

Simulation of the metabolism of absorbed energy-yielding nutrients in young sheep: efficiency of utilization of lipid and amino acid.

A previously described mathematical model that simulates the metabolism of absorbed nutrients in a sheep weighing 25 kg was used to examine the effects of altering lipid and amino acid absorption, and the potential of the animal to deposit protein on the efficiency of utilization (kf) of metabolizable energy. The predicted kf of energy from lipid added to several diets ranged from 0.65 to 0.74 and was influenced by both the protein and glucose content of the diet. The highest efficiency occurred when body protein deposition was limited by amino acid absorption. Lower values occurred with high protein diets when the proportion of body energy deposited as fat declined and, with low protein diets, when NADPH supply limited the synthesis of fatty acids from acetyl-CoA. Predicted kf of energy from amino acid added to several diets ranged from 0.003 to 0.47. Low values occurred when protein synthesis was limited by amino acid absorption; an increase in amino acid supply increased ATP utilization for protein synthesis and substantially reduced fat deposition with little resulting change in energy retention. The higher values occurred when most of the additional amino acid was oxidized. Glucose supply increased the kf of added amino acid primarily by reducing the synthesis of glucose from amino acids. Predicted kf of a whole diet generally declined as the proportion of protein in the diet increased. However, when the balance of absorbed nutrients was such that fat synthesis was limited by the supply of NADPH, kf increased with increasing dietary protein. Predicted kf of a diet also declined when the proportion of body energy deposited as protein increased, except when fat synthesis was limited by the supply of NADPH. The predictions suggest that kf is determined primarily by the energetic efficiency of biochemical reactions for maintenance and growth. However, most kf values less than 0.5 were associated with a flux of more than 1 g mol/d of ATP through the degradation pathway (representing substrate cycles) that occurred when NADPH supply limited the synthesis of fatty acids from acetyl-CoA.

Absorption↗