Paul C. Herrmann

A Functional Model of Cytochrome c Oxidase: Thermodynamic Implications

The environment of the CuI ion in the distal ligand group decides the fate of the reduction of O2 by the two analogues 1 and 2 of the heme a3  CuB center in cytochrome c oxidase. The fourfold coordination by N in 1 favors the CuII oxidation state and leads to a 4 e- -4 H+ reduction and the formation of H2 O under physiological conditions, while with 2 a 2 e- -2 H+ reduction occurs to form the cytotoxic H2 O2 .

Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration

Platelets are important mediators of blood coagulation that lack nuclei, but contain mitochondria. Although the presence of mitochondria in platelets has long been recognized, platelet mitochondrial function remains largely unaddressed. On the basis of a small amount of literature that suggests platelet mitochondria are functional, we hypothesized that the inhibition of platelet mitochondria disrupts platelet function and platelet-activated blood coagulation. To test this hypothesis, members of the tetrazole, thiazole, and 1,2,3-triazole families of small molecule heterocycles were screened for the ability to inhibit isolated mitochondrial respiration and coagulation of whole blood. The families of heterocycles screened were chosen on the basis of the ability of the heterocycle family to inhibit a biomimetic model of cytochrome c oxidase (CcO). The strength of mitochondrial inhibition correlates with each compounds ability to deter platelet stimulation and platelet-activated blood clotting. These results suggest that for this class of molecules, inhibition of blood coagulation may be occurring through a mechanism involving mitochondrial inhibition.

Functional models for the oxygen binding/activating hemeproteins, myoglobin and cytochrome c oxidase

Abstract Hemoproteins (hemoglobin and myoglobin) reversibly bind O 2 for transport and storage; other heme proteins (cytochrome c oxidase) reduce O 2 to water and couple the energy from that reaction to create a proton gradient for the eventual synthesis of ATP. This paper will describe the design and synthesis of iron porphyrins which are functional models for these oxygen binding and activating heme proteins.

Extreme Plasma Dilution Decreases Heparin and Protamine Cardiopulmonary Bypass Requirements: A Case Report on a Jehovah's Witness Patient

The primary focus of cardiopulmonary bypass management in Jehovahs Witness patients is the need to conserve blood. A consequence of these strategies inevitably results in hemodilution that is frequently extreme enough to dilute clotting factors and potentially impair coagulation. The purpose of this case report is to demonstrate that a hemodiluted patient requires less heparin to sustain anticoagulation and less protamine to reverse heparin at cardiopulmonary bypass termination. Patient harm may ensue unless the effects of extreme hemodilution are recognized.