Reaction velocities in vivo: standardization of kinetic "constants" by correction for blood flow.

1. The results of kinetic studies in vitro are difficult to apply to metabolic reactions in vivo. 2. In living vertebrates reaction rates are usually first-order and for a particular reaction the rate "constant", k, varies with the several thousand-fold variations in metabolic rate. 3. Therefore, in the kinetic equation (formula: see text) since K varies with metabolic rate, Vmax and/or Km will aslo vary. 4. However, reaction rates for a series of different substrates were similar in animals varying widely in metabolic rate if corrections were made for differences in blood flow. 5. The observation that metabolic rate (reaction rate) is directly dependent on blood flow (Coulson et al., 1977) allowed derivation of new kinetic constants which were valid in vivo. 6. Introduction of a flow term into the observed first-order equations yields an "affinity constant", K, or a "flow constant", KF, somewhat analogous to Km, which allows one to predict reaction rates in animals of different metabolic rates. 7. The defining equations are (formula: see text) where V = reaction velocity in mmol/hr/kg tissue, [S] = millimolar substrate concentration in the blood, k = In 2/tau (tau the half-life) and F = blood flow in 1/hr/kg tissue. 8. Thus, K = k/F = 1/KF. The KF's for the initial step in the degradation of 17 amino acids in rats, dogs, lizards, turtles and alligators were similar, demonstrating the similarity of enzyme affinities in different species.