WHOLE-BODY PROTEIN-METABOLISM IN HUMAN PULMONARY TUBERCULOSIS AND UNDERNUTRITION - EVIDENCE FOR ANABOLIC BLOCK IN TUBERCULOSIS

1, Differing patterns of protein metabolism are seen in wasting due to undernutrition and wasting due to chronic infection, 2, We investigat ed whole body energy and protein metabolism in nine subjects with pulm onary tuberculosis, six undernourished subjects (body mass index < 18. 5 kg/m(2)) and seven control subjects from an Indian population, Fasti ng subjects were infused with L-[1-C-13]leucine (2.3 mu mol . h(-1) . kg(-1)) for 8 h, 4 h fasted then 4 h fed, Leucine kinetics were derive d from C-13-enrichment of leucine and alpha-ketoisocaproic acid in pla sma and CO2 in breath, 3, Undernourished subjects, but not tuberculosi s subjects, had higher rates of whole body protein turnover per unit l ean body mass than controls [163,1+/-9,4 and 148.6+/-14.6 mu mol compa red with 142.8+/-14.7 mu mol leucine/h per kg, based on alpha-ketoisoc aproic acid enrichment (P = 0.039)1, 4, In response to feeding, protei n oxidation increased in all groups, Tuberculosis subjects had the hig hest fed rates of oxidation (47.0+/-10.5 compared with 37.1+/-5.4 mu m ol . h(-1) . kg(-1) in controls), resulting in a less positive net pro tein balance in the fed phase (controls, 39.7+/-6.2; undernourished su bjects, 29.2+/-10.6; tuberculosis subjects, 24.5+/-9.3 P= 0.010), Thus fed-phase tuberculosis subjects oxidized a greater proportion of leuc ine flux (33.2%) than either of the other groups (controls, 24,0% unde rnourished subjects, 24.0%; P = 0.017), 5, Tuberculosis did not increa se fasting whole body protein turnover but impaired the anabolic respo nse to feeding compared with control and undernourished subjects, Such 'anabolic block' may contribute to wasting in tuberculosis and may re present the mechanism by which some inflammatory states remain refract ory to nutrition support.