Variable ATP yields and uncoupling of oxygen consumption in human brain

Area of Science:

• Neuroscience
• Metabolic Research
• Human Physiology

Background:

• Brain oxidative metabolism exhibits significant variability in healthy humans, despite reflecting stable brain function.
• This variability suggests potential differences in the efficiency of energy utilization, specifically ATP turnover and oxygen consumption.

Purpose of the Study:

• To test the hypothesis that a substantial portion of human brain oxygen consumption is conserved across individuals.
• To quantify the variability in regional cerebral metabolic rate for oxygen (rCMRO2) in a healthy adult population.

Main Methods:

• Measured rCMRO2 in 50 healthy volunteers (aged 21-66), normalizing values to a common age of 25.
• Normalized regional metabolic rates to the population average for each subject and brain region.
• Calculated coefficients of variation for different brain regions.

Main Results:

• Coefficients of variation for normalized rCMRO2 ranged from 10% to 15% across brain regions.
• Normalized regional metabolic rates varied from 70% to 140% of the population average, indicating a two-fold variation.
• The conserved oxygen metabolism coupled to ATP turnover is estimated to be no more than 70% of the population's average oxygen consumption.

Conclusions:

• A significant portion of brain oxygen consumption is conserved across healthy individuals, supporting the hypothesis.
• Variability in total brain oxygen consumption is largely attributable to differences in metabolic efficiency or uncoupling.
• Findings provide a threshold for conserved ATP-coupled oxygen metabolism in the human brain.