Interrelations in the Oxidative Metabolism of Free Fatty Acids, Glucose, and Glycerol in Normal and Hyperlipemic Patients A COMPARTMENTAL MODEL

C. L. Malmendier; C. Delcroix; M. Berman

doi:10.1172/JCI107782

Interrelations in the Oxidative Metabolism of Free Fatty Acids, Glucose, and Glycerol in Normal and Hyperlipemic Patients A COMPARTMENTAL MODEL

C. L. Malmendier, C. Delcroix, and M. Berman

Published August 1, 1974 - More info

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Abstract

Palmitate, glucose, and glycerol oxidation to CO₂ have been investigated in the fasted state in ten normal subjects and nine patients (six hyperlipoproteinemias, one xanthomatosis, and two glycogenosis) after intravenous injection of [1-¹⁴C]palmitate, [1-¹⁴C]glucose, or [1-¹⁴C]glycerol in tracer amounts. The specific activities and concentrations of plasma palmitate, glycerol, or glucose and expired CO₂ were measured at various intervals after the injection for a period of 24 h. All the studies were analyzed in terms of a multicompartment model describing the structure for each of the subsystems, the transfer of carbon label between subsystems, and the oxidation to CO₂. A bicarbonate subsystem was also included in the model to account for its role in shaping the CO₂ curves.

All the CO₂ activity following a palmitate injection could be accounted for by a direct oxidative pathway from plasm FFA with the addition of a 20-min delay compartment. The same also applied to glucose, except that the delay compartment had a mean time of about 150 min. Only about a third of the injected glycerol was directly oxidized to CO₂ from plasma; the delay time was about 4 min. Most of the remainder was converted to glucose.

In normals about 45% of the FFA is oxidized to CO₂ directly. This constitutes about 30% of the total CO₂ output. In hyperlipemia the CO₂ output is nearly unchanged and the contribution from FFA is nearly the same. There is a considerable increase (factor of 2), however, in FFA mobilization, most of which is probably diverted to triglyceride synthesis.

The glucose and glycerol subsystems are roughly the same in normals and hyperlipemics. About 50% of glucose is oxidized by the direct pathways which accounts for about 35% of the CO₂ output. Glycerol accounts for only 1.5% of the CO₂ produced.

Major changes occurred in the glycerol and glucose subsystems in glycogenosis. The changes are consistent with the known deficiency in glucose-6-phosphatase in this disorder. There is a considerable reduction (factor of 2 or more) in the release of glucose to plasma (gluconeogenesis) and in the conversion of glycerol to glucose.

Despite the integration of the kinetics of the glucose, glycerol, and FFA subsystems over a 24-h period, 36% of the CO₂ production was still unaccounted for in normals and 50% in hyperlipemics. Thus, some of the carbon must wind up in very slowly turning-over pools which supply CO₂ through subsystems not covered in these studies (triglycerides, glycogen, amino acids, etc.).

All the modeling was carried out with the aid of the SAAM25 computer program.