Polysaccharide Sequence Influences the Specificity and Catalytic Activity of Glucuronyl C5-Epimerase.

Heparin is a widely used biotherapeutic produced from animal tissues. However, it might be possible to produce a bioengineered version using a multienzyme process, relying on the isolation of the K5 capsule heparosan and its chemical conversion to sulfoheparosan, NSH. Glucuronyl C5-epimerase, the first enzyme that acts on NSH, catalyzes the reversible conversion of glucuronic acid (GlcA) to iduronic acid (IdoA).

Elucidating the unusual reaction kinetics of D-glucuronyl C5-epimerase.

The chemoenzymatic synthesis of heparin, through a multienzyme process, represents a critical challenge in providing a safe and effective substitute for this animal-sourced anticoagulant drug. D-glucuronyl C5-epimerase (C5-epi) is an enzyme acting on a heparin precursor, N-sulfoheparosan, catalyzing the reversible epimerization of D-glucuronic acid (GlcA) to L-iduronic acid (IdoA). The absence of reliable assays for C5-epi has limited elucidation of the enzymatic reaction and kinetic mechanisms.

Metabolic engineering of Bacillus megaterium for heparosan biosynthesis using Pasteurella multocida heparosan synthase, PmHS2.

Background: Heparosan is the unsulfated precursor of heparin and heparan sulfate and its synthesis is typically the first step in the production of bioengineered heparin. In addition to its utility as the starting material for this important anticoagulant and anti-inflammatory drug, heparosan is a versatile compound that possesses suitable chemical and physical properties for making a variety of high-quality tissue engineering biomaterials, gels and scaffolds, as well as serving as a drug delivery vehicle. The selected production host was the Gram-positive bacterium Bacillus megaterium, which represents an increasingly used choice for high-yield production of intra- and extracellular biomolecules for scientific and industrial applications.

Heavy Heparin: A Stable Isotope-Enriched, Chemoenzymatically-Synthesized, Poly-Component Drug.

Heparin is a highly sulfated, complex polysaccharide and widely used anticoagulant pharmaceutical. In this work, we chemoenzymatically synthesized perdeuteroheparin from biosynthetically enriched heparosan precursor obtained from microbial culture in deuterated medium. Chemical de-N-acetylation, chemical N-sulfation, enzymatic epimerization, and enzymatic sulfation with recombinant heparin biosynthetic enzymes afforded perdeuteroheparin comparable to pharmaceutical heparin.

Engineered heparins as new anticoagulant drugs.

Heparin is an anionic polysaccharide that is widely used as a clinical anticoagulant. This glycosaminoglycan is prepared from animal tissues in metric ton quantities. Animal-sourced heparin is also widely used in the preparation of low molecular weight heparins that are gaining in popularity as a result of their improved pharmacological properties.

Serum phosphate in acute myocardial infarction.

The aim of this study is to measure phosphate levels in AMI, compare and analyse its relation with left ventricular (LV) dysfunction and mortality. Serum phosphate was measured by kinetic assay method in 40 patients with acute myocardial infarction (AMI). Echocardiographic LV function was assessed in all and the patients were followed up for 30 days.

Angiographic correlates of anterior ST segment depression in acute inferior wall myocardial infarction.

This study was conducted prospectively to assess the correlation between the pattern of anterior ST segment depression on the admission electrocardiogram and the in-hospital morbidity and mortality in patients with acute inferior wall myocardial infarction. Coronary angiography was also done to assess its correlation, if any, with pattern of anterior ST segment depression. Our study cohort comprised of 165 consecutive patients with acute inferior wall myocardial infarction divided into four groups based on admission electrocardiogram.

Type D double aortic arch. Double aortic arch with interruption of its left component proximal to the site of origin of left common carotid artery.

Type D double aortic arch in a five year old boy (with interruption of left arch proximal to left common carotid artery)--with persistent ductus arteriosus and stenosis of right and left pulmonary arteries diagnosed during life is reported. At surgery for P.D.