Isovaleraldehyde

Endpoint summary

Additional information

Studies with the main objective to investigate the metabolism of isovaleraldehyde could not be identified. But determinations of plasma levels in rats and humans have been conducted in three studies concerned with investigations related to the disease hepatic encephalopathy. It was demonstrated that isovaleraldehyde is a natural constituent in blood. It originates at least in part from the catabolism of leucine. In rats, colonic bacteria seem to be involved in the formation of isovaleraldehyde while in humans evidence was negative for the participation of colonic bacteria in the formation of isovaleraldehyde.

 

Kubow 1981

 

Isovaleraldehyde is naturally present in the plasma of rats and humans at levels of ca. 0.5 to 0.6 mg/L (6 to 7 µmol/L). It is formed at least partly from leucine by gut bacteria (result of a feeding experiment with leucine and neomycin). Further information is not available if there are other sources and if isovaleraldehyde is additionally produced endogenously by mammalian cells/tissues.

 

Marshall 1985

 

3-Methylbutanal (isovaleraldehyde) is naturally present in the plasma of healthy human subjects and of patients with chronic liver disease at levels of ca. 0.116 and 0.125 µmol/L respectively. No statistically significant differences in plasma levels were found between control subjects and patients and between fasted and non fasted subjects or patients.

After intake of leucine (9.5 g over 10 min) plasma leucine and 3-methylbutanal levels increased with peak concentration after ca. 100 to 120 min (ca. 3-fold and 10-fold increase respectively). Neomycin had no effect on the results of leucine ingestion.

 

Mardini 1987

 

In the blood of healthy control subjects, isovaleraldehyde was present in a mean plasma concentration of 0.17 µmol/L (SEM 0.02). Patient with liver diseases had significantly increased plasma levels (0.58 µmol/L) compared to controls. But within patients, differences were not significant.

 

Roberts 1991

 

In an additional study, the deformylation reaction of C3 to C5 aldehydes resulting in olefin formation was investigated using a reconstituted system of different cytochrom P-450 isozymes. This reaction is not a major metabolic pathway of C3 to C5 aldehydes. For isovaleraldehyde, this reaction has no relevance in the in vivo metabolism according to the reaction rate determined (see below).

 

In order to achieve deformylation and formation of the corresponding olefin, branching at the α-carbon atom was required. Activity increased with increasing branching (trimethylacetaldehyde > 2-methylbutyraldehyde > butyraldehyde). The relative activities of the P-450-isozymes studied are dependent on the substrate tested, varying isozymes being most active with different substrates.

 

For isovaleraldehyde with branching at the ß-position, the olefinic reaction product could be detected but the reaction rate was very low (below the limit of detection; < 12 pmol of product per min per nmol of P-450).