title: Quantitative relationship between autophagy and proteolysis during graded amino acid deprivation in perfused rat liver.
abstract: Fractional volumes of lysosomal-vacuolar elements and long lived protein degradation were quantitatively correlated in rat livers perfused in the single pass mode with varying levels of plasma amino acids. Volumes were determined stereologically; degradation was measured in a second stage cyclic perfusion from the linear accumulation of valine in the presence of cycloheximide and was corrected for loss of short lived proteins. Livers exhibited a high degree of amino acid responsiveness; total protein degradation decreased sharply from 4.5 to 1.5%/h (basal) over an amino acid range of 0-10 times (10X) normal plasma concentrations; near basal values were achieved at 1X. Vacuoles containing undegraded cytoplasm (AVi) appeared immediately following stringent deprivation and by 7.5 min were converted to degradative forms (AVd); both autophagic populations attained steady state volumes by 20 min. With amino acid additions, AVi formation virtually ceased and AVd regressed rapidly (0.087 min-1). Cytoplasmic turnover, calculated from this rate constant and the increases over basal in fractional volumes of either AVi or degradative components, agreed quantitatively with corresponding rates of protein turnover. Predictions from these findings, together with evidence for intralysosomal protein pools in both deprived and basal states, account fully for the accelerated proteolysis and suggest that cytoplasm is also internalized by lysosomes under basal conditions.
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D010477:Perfusion; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000596:Amino Acids; D007328:Insulin; D011506:Proteins