Download 0604 Role of mitochondria in the control of fatty acid oxidation

0604 Role of mitochondria in the control of fatty acid oxidation
SAHLIN K The Swedish School of Sport and Health Sciences (GIH), Stockholm, Sweden,
Institute of Sport Sciences and clinical Biomechanics, University of Southern Denmark
High capacity for fatty acid (FA) oxidation is a sign of metabolic fitness and is important not
only for exercise performance but also for health promotion. FA oxidation is controlled by
multiple mechanisms e.g. substrate availability, transport over sarcolemma and transport into
mitochondrial matrix. FA oxidation increases with the intensity of the exercise but reaches a
peak at about 40- 60% of VO2max after which it is reduced. The mechanism for the crossover
from FA to CHO at high exercise intensities is not fully understood. One hypothesis is that
increased glycolytic flux may limit the carnitine-mediated transport of FA into mitochondrial
matrix through inhibition of carnitinepalmitoyl transferase (CPT1). Supporting evidence is the
observed trapping of carnitine as acetyl-carnitine and inhibition of CPT1 by acidosis. Fuel
interaction may also be under control of cellular energy state. The apparent affinity of
mitochondrial respiration for ADP is lower for FA than for pyruvate, which will favour FA
oxidation at low but CHO at high exercise intensities. Further control by energy state may
occur at pyruvate dehydrogenase and acyl-CoA synthetase. Recent studies demonstrate that
additional control of FA oxidation is exerted downstream of CPT1 within mitochondria.
Studies on isolated mitochondria show that the maximal rate of respiration with palmitoylcarnitine (PC) (bypasses CPT1) is (i) influenced by muscle fibre type, (ii) increases after
extreme exercise and (iii) is related to whole body FA oxidation during low-intensity exercise.
The limitation of mitochondrial oxidation of PC and the interaction between CHO and FA
oxidation are unclear and further studies are warranted.