Stereochemistry of enzymic hydrogen transfer to pyridine nucleotides

Determination of the absolute configuration of (-)-(2R)-succinic-2-d acid by neutron diffraction study: unambiguous proof of the absolute stereochemistry of the NAD+/NADH interconversion.

“…At a wavelength of 356 nm and a concentration of 0.5 M, the [a]20 value was found to be -0.89°in aqueous solution. It increased to zero with increasing wavelength to the sodium line (589 nm), which is consistent with Cornforth's and PopjAk's results (6,7). This value ([a]20 = -0.89°) corresponds to approximately 78% deuteration.…”

“…In conclusion, this neutron diffraction analysis provides definitive unambiguous proof that the conclusions of Cornforth and Popjak's study (6) regarding the absolute stereochemistry of the enzymatic NAD+ = NADH interconversion are correct, and it once more demonstrates the usefulness of neutron diffraction in solving problems of this type.…”

“…1). In a landmark experiment (6,7), Comforth, PopjAk, and coworkers (i) chemically degraded the dihydronicotinamide ring (derived from two different sources) into succinic-2-d acid, (ii) prepared an independent batch of succinic-2-d acid from enzymatically labeled deuteriomalic acid, and (iii) compared the optical rotatory dispersion curves of these three forms of succinic-2-d acid, to show that type A enzymes delivered the H atom into the HA position of IV. Thus, the enantiomerically related model V was eliminated.…”

“…This value ([a]20 = -0.89°) corresponds to approximately 78% deuteration. Incomplete deuteration normally occurs in most of these types of reactions (6,7,16).…”

Stereospecificity of hydrogen transfer by the human placental 15‐hydroxy prostaglandin dehydrogenase

“…When tritium is transferred by a dehydrogenase from a substrate to the carbon atom C4 of NAD', a 4 R or 4 S configuration appears depending on the stereospeciticity of the enzyme [4]. Class A dehydrogenases lead to the 4 R configuration, class B dehydrogenases to the 4 S configuration [5].…”