ABSTRACT
Enzymatic catalysis and homogeneous catalysis offer complementary means to address synthetic challenges, both in chemistry and in biology. Despite its attractiveness, the implementation of concurrent cascade reactions that combine an organometallic catalyst with an enzyme has proven challenging because of the mutual inactivation of both catalysts. To address this, we show that incorporation of a d(6)-piano stool complex within a host protein affords an artificial transfer hydrogenase (ATHase) that is fully compatible with and complementary to natural enzymes, thus enabling efficient concurrent tandem catalysis. To illustrate the generality of the approach, the ATHase was combined with various NADH-, FAD- and haem-dependent enzymes, resulting in orthogonal redox cascades. Up to three enzymes were integrated in the cascade and combined with the ATHase with a view to achieving (i) a double stereoselective amine deracemization, (ii) a horseradish peroxidase-coupled readout of the transfer hydrogenase activity towards its genetic optimization, (iii) the formation of L-pipecolic acid from L-lysine and (iv) regeneration of NADH to promote a monooxygenase-catalysed oxyfunctionalization reaction.
Subject(s)
Hydrogenase/chemical synthesis , Hydrogenase/metabolism , Amines/chemistry , Amino Acid Oxidoreductases/metabolism , Catalysis , Colorimetry , Imines/chemistry , Models, Molecular , Molecular Biology , Molecular Structure , Organometallic Compounds/chemistry , Organometallic Compounds/metabolism , Oxidation-Reduction , Protein Isoforms , Proteins/chemistry , Proteins/metabolismABSTRACT
BACKGROUND: Moderate elevations of cardiac troponin (Tn) T, up to levels presumably diagnostic for minor myocardial damage, are suspected to be false positive in nearly 0.3 of end-stage renal disease (ESRD) patients undergoing haemodialysis (HD). It is not clear whether cardiac TnI is superior to TnT in those patients, if differences between ESRD and pre-ESRD occur, and what the prognostic meaning of these troponin elevations might be. SUBJECTS AND METHODS: We examined 40 chronic renaldisease patients [56.4 SD 13.9 years; 22 male, 18 female) without evidence of an acute coronary syndrome (ACS) for at least 28 days prior to the investigation. Cardiac status was determined by history, physical examination, ECG and echocardiography. Patients were divided into subgroups with HD (n = 20) and without HD (n = 20). Patients without HD had a mean creatinine clearance (CC) of 13.45 ml/min. Tn were measured by immunoassay techniques. TnT was compared to two different TnI tests (TnID, TnIB), CK/CKMB activity and myoglobin (MYO) concentrations. In all patients, a 9-month follow-up for acute myocardial infarction, re-hospitalization, and death was completed. RESULTS: None of the troponins significantly predicted patient outcome. Tn did not correlate with CC (r<0.6). Applying the lowest reported threshold values for all tests in the HD group, 0.3 patients were positive for TnT, 0.55 patients were positive for TnID, and 0.15 for TnIB. In the group without HD, 0.2 patients were positive for TnT and TnID and 0.1 for TnIB. CONCLUSIONS: Moderate elevations of cardiac troponins are common in clinically stable patients with renal disease and are neither diagnostic for an acute coronary syndrome nor predictive of outcome. It is concluded that increased troponins in asymptomatic renal patients are of questionable value for risk stratification, most probably due to unspecific elevations.
Subject(s)
Kidney Failure, Chronic/metabolism , Troponin I/analysis , Troponin T/analysis , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , PrognosisABSTRACT
The nurse's role in this relatively safe, effective procedure is to prepare equipment, monitor for possible adverse effects, and support the mother.