Alcohols, C12-14

Biotransformation and kinetics

Administrative data

Endpoint:

biotransformation and kinetics

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Higher alcohols bioconcentration: Influence of biotransformation.

Author:

de Wolf W, Parkerton T

Year:

1999

Bibliographic source:

Preprints of Extended Abstracts 39: 101-103. Presented in the session Persistent, Bioaccumulative, Toxic Chemicals: Food Chain Transfer and exposure, part 1 at the American Chemical Society Symposium, Anaheim, CA March 21-25, 1999.

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Alcohols, C12-14

EC Number:

279-420-3

EC Name:

Alcohols, C12-14

Cas Number:

80206-82-2

Molecular formula:

C13H28O

IUPAC Name:

Alcohols, C12-14

Results and discussion

Any other information on results incl. tables

Fatty alcohols can be metabolized by alcohol dehydrogenase and aldehyde dehydrogenase to fatty acids. Alcohol dehydrogenase is found in the soluble fraction of various   tissues. The coenzyme is normally NAD, and although NADP may be utilized, the rate of the reaction is slower. The enzyme is relatively non-specific and so accepts a wide variety of substrates including exogenous primary and secondary alcohols, with primary alcohols being metabolized at a faster rate. The product of the oxidation is the corresponding aldehyde if the substrate is a primary alcohol or a ketone if a secondary alcohol is oxidized. The aldehyde produced by this oxidation may be further oxidized by aldehyde dehydrogenase to the corresponding acid. This enzyme also requires NAD and is found in the soluble fraction. Other enzymes may also be involved in the oxidation of aldehydes, particularly aldehyde oxidase and xanthine oxidase. These enzymes are primarily cytosolic, although microsomal aldehyde oxidase activity has been detected. They are flavoproteins, containing FAD and also molybdenum, and the oxygen incorporated is derived from water rather than oxygen. Aldehyde oxidase and xanthine  oxidase both oxidize a wide variety of substrates.

                 

Occurence: The alcohol dehydrogenase enzyme system is ubiquitously present in the plant and animal kingdom. It has been specifically identified in man and in different species e.g. cod, fathead minnows, carp, eel, sardines, rainbow trout, rat, mice, and several plant sources. Aldehyde dehydrogenase is also ubiquitously present.

           

 First pass effect and main enzyme activity: In the caecum of freshwater gourami (Trichogaster cosby), metabolism of hexadecanol to hexadecanoic acid occurred during absorption. The first reaction in the sequence fatty alcohol-aldehyde-acid seems to occur under physiological conditions at a much slower rate than the second reaction so that free aldehyde is not detected. Also in rat, fatty alcohols are absorbed as fatty acids and fatty acid esters, particularly triglycerides. The highest alcohol dehydrogenase activity for rainbow trout and the carp is found in the liver, similar to organisms like man, rhesus monkey, horse, porpoise, rat, domestic fowl, frog and pike.In contrast, virtually all ADH in the goldfish is found in the red and white muscles.

                 

Rates and specificity: For a series of C4-C16 alcohols, the apparent Km values show a steady decrease with increasing  hydrophobicity, whereas the maximum rates of oxidation  remain similar. This suggests that enzyme-substrate binding is governed largely by apolar interactions.