Regulation of alpha-ketoisocaproate binding to albumin in vivo by free fatty acids

Am J Physiol. 1982 Jan;242(1):E67-71. doi: 10.1152/ajpendo.1982.242.1.E67.


The importance of alpha-keto acid binding to plasma proteins was investigated both in vitro and in vivo using alpha-ketoisocaproate (KIC), the alpha-keto acid of leucine. Gel chromatography indicated that 65% of the radioactivity comigrated with serum albumin. An ultrafiltration assay was developed to estimate the percentage of free and bound KIC. These percentages, along with total plasma KIC concentrations, were used to calculate the circulating concentrations of free and bound KIC. KIC or free fatty acids (FFA) displaced [14C]KIC bound to bovine albumin or whole plasma. KIC was totally displaced from plasma proteins by 10 mM oleate, stearate, and myristate; whereas the alpha-keto acids of isoleucine and value were 50 and 85%, respectively, as effective as KIC. To determine whether increased plasma FFA concentrations alter the binding of KIC to plasma proteins in vivo, five postabsorptive humans were infused with triglyceride and heparin during the simultaneous administration of somatostatin, glucagon, and insulin. During the FFA elevation, plasma leucine decreased by 9% (P less than 0.02). Total plasma KIC remained constant, whereas free KIC increased (P less than 0.02) and bound KIC decreased (P less than 0.001). These results indicate that KIC is bound to plasma albumin in vivo and suggests that FFA, by altering circulating free KIC concentrations, may influence protein metabolism in man.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • Blood Glucose / analysis
  • Blood Proteins / metabolism
  • Caproates / blood*
  • Chromatography, High Pressure Liquid
  • Dogs
  • Fatty Acids, Nonesterified / pharmacology*
  • Glucagon / blood
  • Insulin / blood
  • Keto Acids / blood*
  • Kinetics
  • Protein Binding
  • Serum Albumin / metabolism*
  • Serum Globulins / metabolism


  • Blood Glucose
  • Blood Proteins
  • Caproates
  • Fatty Acids, Nonesterified
  • Insulin
  • Keto Acids
  • Serum Albumin
  • Serum Globulins
  • alpha-ketoisocaproic acid
  • Glucagon