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This study was conducted to identify the most rate-limiting amino acids for whole-body protein synthesis in acquired immunodeficiency syndrome (AIDS) patients. We postulated that an essential amino acid that would be rate limiting in AIDS should have a low basal plasma concentration and should remain at a low level during amino acid infusion. Seven male AIDS patients (median age 37 y, CD4 cell count: 76 mm-3) without any clinically active opportunistic infection during the month before the experiment were infused intravenously with a complete amino acid-glucose mixture for 2.5 h. Eight healthy volunteers were used as controls. Before the infusion, the concentrations of most free essential amino acids (methionine, threonine, histidine, isoleucine, leucine and tryptophan) were significantly lower (P < 0.05) in AIDS patients than in controls. Most plasma free essential amino acids increased significantly during infusion. However, the absolute increase above basal levels for threonine, valine, lysine, (P < 0.05) and methionine (P < 0.073) was smaller in AIDS patients than in control subjects. Thus, threonine and possibly methionine may be rate limiting for whole-body protein synthesis in AIDS patients, suggesting that there are selective amino acid requirements in patients with AIDS.

We investigated the responsiveness of protein metabolism to insulin as a mediator of the protein catabolic response to hyperthyroidism in humans. Six healthy volunteers were studied in a postabsorptive state before and after oral intake of thyroid hormones (2 micrograms.kg-1.day-1 L-thyroxine for 6 wk along with 1 microgram.kg-1.day-1 triiodothyronine for the last 2 wk). Insulin was infused at 7.14 nmol.kg-1.min-1 for 140 min under euglycemic and eukalemic clamps. An appropriate amino acid infusion was used to blunt insulin-induced hypoaminoacidemia. Leucine kinetics were assessed using a primed continuous infusion of L-[1-13C]leucine. Hyperthyroidism induced a significant increase (P < 0.05) in leucine endogenous appearance rate (a reflection of proteolysis; 2.15 +/- 0.06 vs. 1.76 +/- 0.03 mumol.kg-1.min-1 in the control state), oxidation (0.54 +/- 0.04 vs. 0.47 +/- 0.07), and nonoxidative disposal (a reflection of protein synthesis; 1.80 +/- 0.06 vs. 1.45 +/- 0.06). Insulin lowered proteolysis. Further hyperthyroidism improved the ability of insulin to inhibit proteolysis, whether considered as an absolute decrease (-0.57 +/- 0.02 vs. -0.45 +/- 0.05 mumol.kg-1.min-1, P < 0.05) or related to insulinemia [1.59 +/- 0.11 vs. 1.01 +/- 0.08 mumol leucine.kg-1.min-1/(nmol insulin/l), P < 0.05]. Insulin also moderately (but significantly P < 0.05) lowered protein synthesis in both control and hyperthyroid states. These changes in insulin action may provide a mechanism to save body protein during hyperthyroidism.

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