Cyclic nucleotide phosphodiesterase activities of the human liver: comparison between control and reye's syndrome samples

Cyclic nucleotide phosphodiesterase activities of the human liver: comparison between control and reye's syndrome samples

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ABSTRACT Summary: The specific activity and kinetic constants of the four forms of cyclic nucleotide phosphodiesterase (PDE) activities of liver obtained at autopsy from patients with and without Reye's syndrome have been analyzed and compared. Assays were conducted on supernatants of 30,000 × _g_ spun homogenates after dialysis to remove endogenously accumulated substrate. Km values were derived by the double reciprocal plot method. A higher mean value for the low affinity cAMP activity is found in Reye's subjects (11.36 ± 7.33 × 10-4 M compared to 3.6 ± 1.73 × 10-4 M for controls). Values for the other forms are similar between groups. Values for controls are: 4.03 ± 1.8 × 10-6 M for the high affinity cAMP PDE activity and 2.57 ± 0.27 × 10-4 M and 8.28 ± 5.74 × 10-8 M for the low plus high affinity cGMP PDE activities. Differences in Vmax values are not statistically significant. At 10 and 500 4mUM cAMP concentrations, infants exhibit the highest specific activities. When all subjects in each group are included in calculation of the mean specific activity, no difference of significance is apparent. If all infant values are excluded from both groups, the mean specific activity of the high Km or low affinity cAMP PDE obtained for Reye's subjects is significantly higher than for control subjects (4.18 ± 2.17 nmol/mg/min compared to 1.52 ± 0.93). Such differences are not observed for the low Km or high affinity cAMP PDE or for the high and low affinity cGMP PDE enzymes. In supernatant fractions from both groups, the presence of 10-6 M cGMP enhanced the cAMP hydrolyzing capacity. Higher concentrations of cGMP are inhibitory for both forms of cAMP PDE. Speculation: These observations raise the distinct possibility that children who develop Reye's syndrome may exhibit an altered responsiveness to the polypeptide hormones which utilize the second messenger system to produce their intracellular effects. SIMILAR CONTENT BEING VIEWED BY OTHERS SPONTANEOUS HYDROLYSIS AND SPURIOUS METABOLIC PROPERTIES OF Α-KETOGLUTARATE ESTERS Article Open access 12 August 2021 BIOCOORDINATION REACTIONS IN COPPER(II) IONS AND PHOSPHOCHOLINE SYSTEMS INCLUDING PYRIMIDINE NUCLEOSIDES AND NUCLEOTIDES Article Open access 04 July 2023 DIVALENT CATIONS IN HUMAN LIVER PYRUVATE KINASE EXEMPLIFY THE COMBINED EFFECTS OF COMPLEX-EQUILIBRIUM AND ALLOSTERIC REGULATION Article Open access 29 June 2023 ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pediatrics and Department of Medicine, Division of Gastroenterology, University of Tennessee Center for the Health Sciencies, Ellen S Kang * St. Jude Children's Research Hospital, Memphis, Tennessee, USA Ellen S Kang Authors * Ellen S Kang View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kang, E. Cyclic Nucleotide Phosphodiesterase Activities of the Human Liver: Comparison between Control and Reye's Syndrome Samples. _Pediatr Res_ 12, 761–766 (1978). https://doi.org/10.1203/00006450-197807000-00004 Download citation * Issue Date: 01 July 1978 * DOI: https://doi.org/10.1203/00006450-197807000-00004 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * Adenosine 3′,5′-monophosphate * enzyme kinetics * guanosine 3′,5′-monophosphate phosphodiesterase * Reye's syndrome

ABSTRACT Summary: The specific activity and kinetic constants of the four forms of cyclic nucleotide phosphodiesterase (PDE) activities of liver obtained at autopsy from patients with and


without Reye's syndrome have been analyzed and compared. Assays were conducted on supernatants of 30,000 × _g_ spun homogenates after dialysis to remove endogenously accumulated


substrate. Km values were derived by the double reciprocal plot method. A higher mean value for the low affinity cAMP activity is found in Reye's subjects (11.36 ± 7.33 × 10-4 M


compared to 3.6 ± 1.73 × 10-4 M for controls). Values for the other forms are similar between groups. Values for controls are: 4.03 ± 1.8 × 10-6 M for the high affinity cAMP PDE activity and


2.57 ± 0.27 × 10-4 M and 8.28 ± 5.74 × 10-8 M for the low plus high affinity cGMP PDE activities. Differences in Vmax values are not statistically significant. At 10 and 500 4mUM cAMP


concentrations, infants exhibit the highest specific activities. When all subjects in each group are included in calculation of the mean specific activity, no difference of significance is


apparent. If all infant values are excluded from both groups, the mean specific activity of the high Km or low affinity cAMP PDE obtained for Reye's subjects is significantly higher


than for control subjects (4.18 ± 2.17 nmol/mg/min compared to 1.52 ± 0.93). Such differences are not observed for the low Km or high affinity cAMP PDE or for the high and low affinity cGMP


PDE enzymes. In supernatant fractions from both groups, the presence of 10-6 M cGMP enhanced the cAMP hydrolyzing capacity. Higher concentrations of cGMP are inhibitory for both forms of


cAMP PDE. Speculation: These observations raise the distinct possibility that children who develop Reye's syndrome may exhibit an altered responsiveness to the polypeptide hormones


which utilize the second messenger system to produce their intracellular effects. SIMILAR CONTENT BEING VIEWED BY OTHERS SPONTANEOUS HYDROLYSIS AND SPURIOUS METABOLIC PROPERTIES OF


Α-KETOGLUTARATE ESTERS Article Open access 12 August 2021 BIOCOORDINATION REACTIONS IN COPPER(II) IONS AND PHOSPHOCHOLINE SYSTEMS INCLUDING PYRIMIDINE NUCLEOSIDES AND NUCLEOTIDES Article


Open access 04 July 2023 DIVALENT CATIONS IN HUMAN LIVER PYRUVATE KINASE EXEMPLIFY THE COMBINED EFFECTS OF COMPLEX-EQUILIBRIUM AND ALLOSTERIC REGULATION Article Open access 29 June 2023


ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pediatrics and Department of Medicine, Division of Gastroenterology, University of Tennessee Center for the Health


Sciencies, Ellen S Kang * St. Jude Children's Research Hospital, Memphis, Tennessee, USA Ellen S Kang Authors * Ellen S Kang View author publications You can also search for this author


inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kang, E. Cyclic Nucleotide Phosphodiesterase Activities of the Human Liver:


Comparison between Control and Reye's Syndrome Samples. _Pediatr Res_ 12, 761–766 (1978). https://doi.org/10.1203/00006450-197807000-00004 Download citation * Issue Date: 01 July 1978 *


DOI: https://doi.org/10.1203/00006450-197807000-00004 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable


link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * Adenosine 3′,5′-monophosphate * enzyme


kinetics * guanosine 3′,5′-monophosphate phosphodiesterase * Reye's syndrome