ABSTRACT
Pulmonary arterial hypertension (PAH) is a complex disease with significant morbidity and mortality. Recent animal and human studies have highlighted abnormalities in regulation and metabolism of insulin, sex hormones, adipokines and lipids that may play a role in disease development. Mouse studies suggest features of the metabolic syndrome (MS) including insulin resistance, deficiencies in peroxisome proliferator-activated receptor γ and apolipoprotein E, and low adiponectin are linked to development of PAH. In humans, insulin resistance, the MS and low levels of high-density lipoprotein have been associated with PAH. In addition, abnormal metabolism of oestrogens has been demonstrated in human and animal models of PAH, suggesting an important relationship of sex hormones and pulmonary vascular disease. Improved understanding of how metabolic and hormonal derangements relate to development and progression of pulmonary hypertension may lead to better disease therapies and understanding of potential risk factors. This review will focus on the animal and human data regarding metabolic and sex hormone derangements in PAH.
Subject(s)
Hypertension, Pulmonary/physiopathology , Adipokines/physiology , Animals , Dyslipidemias/physiopathology , Gonadal Steroid Hormones/blood , Humans , Hypertension, Pulmonary/blood , Insulin Resistance/physiology , Metabolic Syndrome/diagnosis , Metabolic Syndrome/physiopathology , Mice , Sex FactorsABSTRACT
1. IMP dehydrogenase (EC 1.1.1.205) from porcine thymus glands has been purified to homogeneity. 2. The enzyme has a subunit MW of 57 kDa and an amino acid composition similar to those obtained from other normal and cancerous mammalian cells. 3. The apparent Km values at pH 8.0 for IMP and NAD+ are 7 and 16 microM, respectively. 4. GMP, XMP and AMP are competitive inhibitors towards IMP and Ki values of 50, 85 and 282 microM, respectively. 5. The effectiveness of nucleotides to protect inactivation by CI-IMP is IMP > GMP > XMP > AMP.
Subject(s)
IMP Dehydrogenase/isolation & purification , Thymus Gland/enzymology , Adenosine Monophosphate/pharmacology , Amino Acids/analysis , Animals , Chromatography, High Pressure Liquid , Electrophoresis, Polyacrylamide Gel , Enzyme Induction/drug effects , Guanosine Monophosphate/pharmacology , Hydrogen-Ion Concentration , IMP Dehydrogenase/chemistry , IMP Dehydrogenase/metabolism , Inosine Monophosphate/metabolism , Inosine Monophosphate/pharmacology , Molecular Weight , NAD/metabolism , Ribonucleotides/pharmacology , Swine , XanthineABSTRACT
Guanine aminohydrolase (EC 3.5.4.3) from rabbit brain, intestine, and liver has been purified to homogeneity by affinity chromatography at room temperature and 0-4 degrees C. In all cases the recovery and fold purification was greatest for purification at room temperature. Each enzyme has a subunit mol. wt of 49,500 and crosslinking studies revealed the native form to be a dimer. The amino acid analysis showed a high content of asx, glx, ser, gly and leu; the pI was 5.0 for each prep. The Michaelis constants at pH 8.0 were 6.1, 6.1 and 5.8 X 10(-6) M for brain, intestine and liver GAH respectively. The enzymes had a broad pH activity profile with an optimum of pH 8.0-8.5.
