Role of mitochondria in hepatic fructose metabolism.
During metabolism of fructose at concentrations exceeding 5 mM, isolated liver cells accumulate fructose 1-phosphate and lose ATP. At added bicarbonate concentrations below 10 mM in the incubation medium, the addition of atractyloside (or carboxyatractyloside) causes a significant net accumulation of 2-phosphoglycerate, resulting in an increase in the ratio 2-phosphoglycerate: 3-phosphoglycerate from below 1 to greater than 5. Digitonin fractionation revealed that virtually all this 2-phosphoglycerate is associated with the mitochondrial fraction, where it achieves a concentration estimated to be about 40 mM. The amount of 2-phosphoglycerate that accumulates is directly related to the initial concentration of fructose. With DL-glyceraldehyde in place of fructose, an even greater accumulation of 2-phosphoglycerate occurs, and this is also dependent upon both the presence of atractyloside and low bicarbonate. Formation of 2-phosphoglycerate is also observed when isolated mitochondria from rat liver are incubated together with glyceraldehyde and an energy source. The obligatory role of atractyloside for the accumulation of 2-phosphoglycerate within intact cells indicates the involvement of the mitochondrial adenylate translocator in this process, possibly as a carrier directly responsible for 2-phosphoglycerate egress from the mitochondrial matrix. If this is so, competition between 2-phosphoglycerate and ATP for egress from the matrix would be predicted to further exaggerate the fructose-induced depletion of cytosolic ATP.
Grivell
A R
AR
Department of Medical Biochemistry, School of Medicine, Flinders University of South Australia, Adelaide.
Halls
H J
HJ
Berry
M N
MN
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D001278:Atractyloside / Q000502:physiology; D001639:Bicarbonates / Q000494:pharmacology; D005632:Fructose / Q000378:metabolism* / Q000502:physiology; D005985:Glyceraldehyde / Q000494:pharmacology; D005988:Glyceric Acids / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D001639:Bicarbonates; D005988:Glyceric Acids; D001278:Atractyloside; C008885:2-phosphoglycerate; D005632:Fructose; D005985:Glyceraldehyde; D000255:Adenosine Triphosphate