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Platelet and fibroblast monoamine oxidase in alcoholism
Abstract:
Monoamine oxidase (MAO) activity has been reported to be low in platelets (MAO B) and brain (MAO A and B) of some patients with alcoholism compared to control subjects. Whether the decreased platelet MAO activity found in alcoholism is secondary to the effect of alcohol or exists before alcohol abuse is not clear. The hypothesis that altered MAO A activity is determined by an abnormality in the genetic regulation of the enzyme can be tested by measuring MAO A activity in human fibroblasts cultured under controlled conditions. We first studied the kinetic parameters of platelet MAO B activity in patients hospitalized for treatment of alcoholism. Vmax was 38% lower in the patients (n = 14) than in normal controls (n = 22), but the enzyme affinity (Km) for the substrate tyramine was unchanged. Patients with the five lowest levels of platelet MAO activity had MAO activity measured from fibroblasts cultured from skin punch biopsies. Their fibroblast MAO activity was within the normal range, showing a dissociation between platelet MAO B and fibroblast MAO A activities and suggesting that MAO A activity is not low for genetic reasons in alcoholic subjects who do have low platelet MAO B activity.
Insights
Low monoamine oxidase B (MAO B) activity in alcoholic patients may not stem from genetic factors. Fibroblast MAO A activity in these individuals was within normal ranges, suggesting non-genetic causes for reduced platelet MAO B.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Reduced monoamine oxidase (MAO) activity in platelets (MAO B) and brain (MAO A and B) is observed in some alcoholism patients.
- The cause of decreased platelet MAO activity in alcoholism—whether due to alcohol's effects or pre-existing—remains unclear.
Purpose of the Study:
- To investigate if altered monoamine oxidase A (MAO A) activity in alcoholism has a genetic basis.
- To differentiate between alcohol-induced MAO changes and potential genetic predispositions.
Main Methods:
- Kinetic analysis of platelet MAO B activity in hospitalized alcoholism patients (n=14) and controls (n=22).
- Measurement of MAO A activity in cultured fibroblasts from skin biopsies of patients with the lowest platelet MAO activity.
Main Results:
- Platelet MAO B Vmax was 38% lower in patients versus controls; enzyme affinity (Km) for tyramine remained unchanged.
- Fibroblast MAO A activity in patients with low platelet MAO B was within the normal range.
- Demonstrated a dissociation between platelet MAO B and fibroblast MAO A activities.
Conclusions:
- Low platelet MAO B activity in alcoholism is likely not due to genetic abnormalities in MAO A.
- Suggests that the reduced MAO B activity in some alcoholic individuals may be secondary to alcohol consumption or other non-genetic factors.