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Biomedical subjects

C I Pogson

Publications and source records attributed to C I Pogson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Quantitative studies of sulphate conjugation by isolated rat liver cells using [35S]sulphate.

We have developed a simple, rapid and sensitive method for the study of sulphate conjugation in isolated liver cells based on the incorporation of 35S from [35S]sulphate. Excess [35S]sulphate is removed by a barium precipitation procedure, leaving [35S]sulphate conjugates in solution. We have used this method to examine the kinetics of sulphation of N-acetyl-p-aminophenol (acetaminophen), 4-nitrophenol and 1-naphthol in isolated rat liver cells. The efficiency of recovery of the sulphate conjugates was greater than 86%. The method is applicable to the quantitative study of sulphate conjugation of any substrate which forms a sulphate conjugate that is soluble in the presence of barium, without the need for standards or radiolabelled sulphate acceptors.

Acetaminophen↗
PubMed1989

How does displacement of albumin-bound tryptophan cause sustained increases in the free tryptophan concentration in plasma and 5-hydroxytryptamine synthesis in brain?

Models of tryptophan catabolism and binding to serum albumin are presented to explain the observed effect of displacement of tryptophan from albumin on the concentrations of free and bound tryptophan and on the rate of 5-hydroxytryptamine (5-HT) synthesis from tryptophan in the brain. A rapid rate of dissociation of tryptophan from albumin (compared to the transit time of tryptophan through the liver) and a large fractional extraction of the free pool of tryptophan during passage through the liver are shown to be necessary factors in determining the effects observed. Because of the low fractional extraction of free tryptophan in the brain, the synthesis of 5-HT will be dependent only upon the free pool of tryptophan. Dissociation of tryptophan from albumin only causes a sustained increase in 5-HT synthesis in the brain because of the effect that this dissociation has on hepatic tryptophan catabolism and thereby on the free pool of tryptophan.

Animals↗
PubMed1989

The control of aromatic amino acid catabolism and its relationship to neurotransmitter amine synthesis.

The aromatic amino acids are, inter alia, substrates for the synthesis of important neurotransmitters. Although the factors controlling the synthesis of these transmitters are not fully understood, there is evidence that the concentrations, both relative and absolute, of the precursor amino acids in the blood are of some significance. The article reviews the biochemical pathways involved in tryptophan, phenylalanine, and tyrosine metabolism in liver, brain, and other tissues and discusses (1) the major regulatory events in the maintenance of blood concentrations and (2) the effects of diet, load dosing, hormones, and other circulating substances on the fate of the amino acids and on events in the central nervous system.

Amino Acids↗
PubMed1987

The role of insulin in the modulation of glucagon-dependent control of phenylalanine hydroxylation in isolated liver cells.

The stimulation of phenylalanine hydroxylation in isolated liver cells by sub-maximally effective concentrations of glucagon (less than 0.1 microM) is antagonized by insulin (0.1 nM-0.1 microM). This phenomenon is a consequence of a decrease in the glucagon-stimulated phosphorylation of phenylalanine hydroxylase from liver cells incubated in the presence of insulin. The impact of insulin on the phosphorylation state and activity of the hydroxylase is mimicked by incubation of liver cells in the presence of orthovanadate (10 microM). A series of cyclic AMP and cyclic GMP analogues enhanced phenylalanine hydroxylation: in each case insulin diminished the stimulation of flux. These results are discussed in the light of the characteristics of insulin action on other metabolic processes.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

The characteristics and site of inhibition of gluconeogenesis in rat liver cells by bacterial endotoxin. Stimulation of phosphofructokinase-1.

The characteristics and site of inhibition of gluconeogenesis by endotoxin were investigated in liver cells isolated from control and endotoxin-treated rats. Endotoxin treatment was associated with inhibition (40-50%) of gluconeogenesis from lactate plus pyruvate over a range of concentrations of substrate and of oleate and with or without glucose or glucagon. Similar inhibition was observed with asparagine, proline, glutamine, alanine and a substrate mixture, but not with glycerol, glyceraldehyde, dihydroxyacetone or endogenous substrates. There was no change in cellular ATP content or in the rates of ketogenesis or ureogenesis from asparagine, proline or glutamine. Other effects on isotopic fluxes, metabolite contents, enzyme activities and control coefficients were consistent with the suggestion that the effects of endotoxin on gluconeogenesis are exerted at the level of phosphofructokinase-1, and not at phosphoenolpyruvate carboxykinase, pyruvate kinase, pyruvate carboxylase or glucokinase.

Animals↗
PubMed1986

The roles of glucagon, insulin and glucocorticoid hormones in the effects of sublethal doses of endotoxin on glucose homeostasis in rats.

The effects of sub-lethal doses of endotoxin on plasma glucose, glucagon, insulin, glucocorticoids and non-esterified fatty acids (NEFA) were determined in rats. Endotoxin did not change the plasma concentration of glucocorticoids, but blocked the effects of elevated glucocorticoid hormone concentrations on both plasma glucose and hepatic tryptophan dioxygenase activity. Endotoxin increased the plasma concentrations of glucose, glucagon and insulin in rats with basal glucocorticoid concentrations, and changed the observed relationships between glucose, glucagon and insulin in a manner consistent with an increased sensitivity of glucagon secretion to lowered glucose concentrations. At the highest dose of endotoxin used, 20 mg/kg over 6 hr, a substantial decrease (greater than 7-fold) in the insulin/glucagon ratio provides evidence for changes in basal (as opposed to hormone-stimulated) glucose production and/or utilisation in vivo.

Animals↗
PubMed1986

The role of haem in the regulation of rat liver tryptophan metabolism.

At saturating concentrations of tryptophan, the activity of tryptophan 2,3-dioxygenase was the same in isolated liver cells and in extracts with added haematin. Intraperitoneal injection of haematin did not increase tryptophan oxidation in livers subsequently perfused in situ. Preincubation of liver cells with physiological concentrations of tryptophan caused maximal saturation of tryptophan 2,3-dioxygenase with haem in liver cells. In cell-free extracts tryptophan 2,3-dioxygenase exhibited complex kinetics with haem. The results have important implications for the understanding of the role of haem in tryptophan metabolism.

Animals↗
PubMed1986

The effect of fatty acids and starvation on the metabolism of gluconeogenic precursors by isolated sheep liver cells.

Isolated liver cells prepared from fed sheep synthesize glucose from propionate at twice the rate observed with cells from starved animals. Addition of palmitate or palmitate + carnitine to incubations of liver cells from starved animals inhibited the rate of glucose synthesis with lactate as a precursor, but had little effect when propionate and pyruvate were substrates. Liver cells from fed and starved sheep synthesized lactate and pyruvate when incubated with propionate. Fatty acids inhibited this formation of lactate and pyruvate from propionate. It is proposed that the different responses of gluconeogenic precursors to fatty acids can be explained by the effect of reducing equivalents on the transport of carbon atoms across the mitochondrial membrane.

3-Hydroxybutyric Acid↗
PubMed1986

The polyamine-dependent modulation of phenylalanine hydroxylase phosphorylation state and enzymic activity in isolated liver cells.

The role of polyamines in the control of phenylalanine hydroxylase phosphorylation state and enzymic activity was investigated. Pre-treatment of liver cells with spermine (1 mM) abolishes the glucagon (1 nM)-stimulated increase in hydroxylase phosphorylation. Concurrently there is a decrease in phenylalanine hydroxylation flux, reflecting decreased enzyme activity; 50% inhibition occurs at approx. 10 microM-spermine. These results are discussed in the context of reports concerning the properties of protein phosphatase 2A.

Animals↗
PubMed1986

Quantification of the importance of individual steps in the control of aromatic amino acid metabolism.

The quantitative importance of the individual steps of aromatic amino acid metabolism in rat liver was determined by calculation of the respective Control Coefficients (Strengths). The Control Coefficient of tryptophan 2,3-dioxygenase for tryptophan degradation was determined in a variety of physiological conditions and with a range of activities of tryptophan 2,3-dioxygenase. The Control Coefficient varied from 0.75 with basal enzyme activity to 0.25 after maximal induction of the enzyme by dexamethasone. The remainder of the control for tryptophan degradation was associated with the transport of the amino acid across the plasma membrane, with only very small contributions from kynureninase and kynurenine hydroxylase. The Control Coefficients of tyrosine aminotransferase for tyrosine degradation were approx. 0.70 and 0.20 with basal and dexamethasone-induced tyrosine aminotransferase activities respectively; the Control Coefficients of the transport of the amino acid into the cell were 0.22 and 0.58 respectively. Phenylalanine hydroxylase was found to have a Control Coefficient for the degradation of phenylalanine of approx. 0.50 under conditions of basal enzyme activity; after maximal activation by glucagon, the Control Coefficient decreased to 0.12. The transport of phenylalanine was responsible for the remaining control in the pathway. These results have important implications, directly for the regulation of aromatic amino acid metabolism in the liver, and indirectly for the regulation of neuroamine synthesis in the brain.

Amino Acids↗