MONOAMINE OXIDASE ACTIVITY IN NORMAL and LESCH‐NYHAN FIBROBLASTS

Abstract

Monoamine oxidase ( M A O ) activity was studied in cultured skin fibroblasts from 10 Lesch-Nyhan patients. a Lesch~ Nyhan tariant and 11 controls matched for age. sex and race. Activity (predominantly type A) was measured in cell homogenates using tryptamine as the substrate. For each line activity varied with the conditions of culture. Activity increased 3-10 fold as cultures went from logarithmic to stationary phase of growth. When cultures were confluent. activity was lowered by frequent feedings or the use of fresh medium and serum. Activity for each line remained fairly stable during successive passages. but rose 3-8 fold as cultures became senescent. When comparing activity between control and Lesch-Nyhan lines. cells were cultured under standardized conditions. The mean value of M A 0 activity in Lesch-Nyhan lines was approximately one fourth of the mean acticity in control lines ( P i 0.012). In the control population. the distribution of activity appeared to be bimodal. Activities in the Lesch-Nyhan lines fell completely within the lower portion of the control distribution. Cells from a Lesch-Nyhan patient who lacked several of the neurologic symptoms of the disease (including self-mutilation) had an M A 0 activity 6 fold greater than the control mean. although his hypoxanthine phosphoribosyltransferase activity was < 3",, of control levels.It appears that: ( I ) M A 0 actility is low in fibroblasts from typical Lesch-Nyhan patients: (2) the severity of neurologic symptoms may be correlated with levels of M A 0 activity: and (3) some interaction between purine and catecholamine metabolism can affect nerve function.

Mutations in the Glucose-6-Phosphatase Gene that Cause Glycogen Storage Disease Type 1a

“…Surprisingly, all three mutant proteins, G6Pase-R83C, G6Pase-R295C, and G6Pase-R83C/R295C, exhibited a higher apparent molecular size and markedly reduced processing of the G6Pase polypeptides (Fig. 4C) (14,15). The results are consistent with disruption of microsomes by freezing that abolishes the translocation requirement.…”

“…Hepatic G6Pase is known to exhibit latency, referring to the portion of enzymatic activity that is not expressed unless the microsomes are disrupted (3,13). Latency values for mannose-6-P phosphohydrolase activity reported for human liver microsomes varied from 23 to 26% (14,15) to 95% (16). Human liver microsomes isolated in the present study exhibited a latency value of 75% (Fig.…”

Constitutional mechanisms of vulnerability and resilience to nicotine dependence

“…In cultured skin fibroblasts, individual responses range from extremely low, almost undetectable, levels to levels 30-fold higher. 145–149 Differences in MAOA activity of up to seven-fold have been noted in postmortem tissues of the human frontal cortex. 149 These individual differences in MAOA activity exist at ages before smoking usually starts.…”

“…149 These individual differences in MAOA activity exist at ages before smoking usually starts. 145,149,150 …”

Mutational analysis of the humanMAOA gene

“…Sequencing of the complete coding region of MAO-A cDNAs was carried out for 10 fibroblast strains from 7 control males and 3 Lesch-Nyhan males, who mani-fested MAO-A activities over a 100-fold range (as measured in previous studies [Edelstein et al, 1978;Costa et al, 19801; Table I). These were compared with previously published sequences for MAOA cDNAs from 2 control males [GM500 and HF53; Hotamisligil and Breakefield, 19911 and from a male affected with mild retardation and impulsive aggressive behavior [Ax, Brunner et al, 1993bl.…”