Rate-law parameters with the best model fit from least-squares analysis compared with experimentally observed ranges and values used for the comparison plots
|
Parameter |
Model |
Experimental |
Graph |
Units |
Source |
|
VmaxAl |
2.2 |
2.0, 2.4-4.7† |
2.2 |
mmol*(min*kg liver)-1 |
a,b |
|
KmA1 |
0.4 |
~1 |
1 |
mM |
c |
|
Vrev |
32.6 |
11-110‡ |
60.5 |
mmol*(min*kg liver)-1 |
d |
|
Krev |
1 |
~1 |
1 |
mM/mM |
d,e |
|
VmaxAc |
2.7 |
- |
2.7 |
mmol*(min*kg liver)-1 |
Estimate |
|
KmAc |
1.2 |
0.2-3 |
1.6 |
mM |
c,f |
†Experimental values of 2.4 and 4.7 mmol*(min*kg liver)-1 were observed at pH 8.5 and 10.5, respectively. Actual activity at physiologic liver pH of 7.5 is expected to be lower because pH 8.5 and 10.5 correspond to the optimal pH of two different forms of alcohol dehydrogenase.
‡Calculated on the basis of a 5- to 50-fold increase in kcat values of forward reaction VmaxAl.
aAdapted from R. F. Derr, Simulation studies on ethanol metabolism in different human populations with a physiological pharmacokinetic model, Journal of Pharmaceutical Sciences 82(7), pp. 677-682, copyright 1993, with permission of John Wiley & Sons.
bAdapted from H. A. W. Wynne, P. Wood, B. Herd, P. Wright, M. D. Rawlins, & O. F. W. James, The association of age with the activity of alcohol dehydrogenase in human liver, Age and Ageing 21(6), pp. 417-420, copyright 1992, with permission of Oxford University Press.
cAdapted from H. Riveros-Rosas, A. Julian-Sanchez, & E. Pina, Enzymology of ethanol and acetaldehyde metabolism in mammals, Archives of Medical Research 28(4), pp. 453-471, copyright 1997, with permission of Elsevier.
dAdapted from W. E. M. Lands, A review of alcohol clearance in humans, Alcohol 15(2), pp. 147-160, copyright 1998, with permission of Elsevier.
eAdapted from J. S. Deetz, C. A. Luehr, & B. L. Vallee, Human liver alcohol dehydrogenase isozymes: reduction of aldehydes and ketones, Biochemistry 23(26), pp. 6822-6828, with permission of the American Chemical Society.
fAdapted from G. S. Peng, M. F. Wang, C. Y. Chen, S. U. Luu, H. C. Chou, T. K. Li, & S. J. Yin, Involvement of acetaldehyde for full protection against alcoholism by homozygosity of the variant allele of mitochondrial aldehyde dehydrogenase gene in Asians, Pharmacogenetics 9(4), pp. 463-476, copyright 1999, with permission of Lippincott Williams & Wilkins.