Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the liver, genes are expressed along a portocentral gradient. Based on their adaptive behavior, a gradient versus compartment type, and a dynamic versus stable type of gradient have been recognized. To understand at least in principle the development and maintenance of these gradients in gene expression in relation to the limited number of signal gradients, we propose a simple and testable model. The model uses portocentral gradients of signal molecules as input, while the output depends on two gene-specific variables, viz., the affinity of the gene for its regulatory factors and the degree of cooperativity that determines the response in the signal-transduction pathways. As a preliminary validity test for its performance, the model was tested on control and hormonally induced expression patterns of phosphoenolpyruvate carboxykinase (PCK), carbamoylphosphate synthetase I (CPS), and glutamine synthetase (GS). Affinity was found to determine the overall steepness of the gradient, whereas cooperativity causes these gradients to steepen locally, as is necessary for a compartment-like expression pattern. Interaction between two or more different signal gradients is necessary to ensure a stable expression pattern under different conditions. The diversity in sequence and arrangement of related DNA-response elements of genes appears to account for the gene-specific shape of the portocentral gradients in expression. The feasibility of testing the function of hepatocyte-specific DNA-response units in vivo is demonstrated by integrating such units into a ubiquitously active promoter/enhancer and analyzing the pattern of expression of these constructs in transgenic mice.
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PMID:A mechanistic model for the development and maintenance of portocentral gradients in gene expression in the liver. 1009 63

Exogenous glucagon increases hepatic glucose synthesis in part by increasing hepatic extraction of amino acids from blood for conversion to glucose. To examine the role of glucagon in orchestrating gene expression of gluconeogenic and ureagenic enzymes, we determined the mRNA concentrations of key hepatic ureagenic and gluconeogenic enzymes at d 11, 15, and 22 postpartum in multiparous Holstein cows that received 0 or 5 mg of glucagon in 60 mL of saline by subcutaneous injection every 8 h for 14 d starting on d 8 postpartum. On d 11 postpartum, glucagon increased the hepatic mRNA concentrations for all measured ureagenic enzymes (carbamoylphosphate synthetase I, ornithine transcarbamylase, and argininosuccinate synthetase) and gluconeogenic enzymes (pyruvate carboxylase and cytosolic and mitochondrial forms of phosphoenolpyruvate carboxykinase) and increased or tended to increase mRNA concentrations of gluconeogenic enzymes on d 15 postpartum but not on d 22. The effect of glucagon to increase mRNA concentrations of ureagenic and gluconeogenic enzymes was limited to times when concentrations of plasma insulin were not increased. Our results suggest that hepatic gene expression of key ureagenic and gluconeogenic enzymes in early-lactation dairy cows is responsive to hormonal regulation by glucagon.
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PMID:Glucagon increases hepatic mRNA concentrations of ureagenic and gluconeogenic enzymes in early-lactation dairy cows. 1976 27