Human apolipoprotein A-I isoprotein metabolism: proapoA-I conversion to mature apoA-I.
ProapoA-I (apoA-i+2 isoform) is the major apoA-I isoprotein secreted by the liver and intestine; however, it is a minor isoprotein in plasma and lymph where the major A-I apo-lipoprotein is mature apoA-I (apoA-I0, apoA-I-1, and apoA-I-2 isoforms). In the present report we provide evidence that apoA-I is rapidly and quantitatively converted to mature apoA-I, and the mature apoA-I isoforms are catabolized at equal rates. In these studies, human proapoA-I was isolated from thoracic duct chylomicrons collected during active fat absorption and mature apoA-I was isolated from plasma high density lipoproteins. The isolated lipoproteins were delipidated, fractionated by gel permeation chromatography, and the individual apoA-I isoforms were separated by preparative isoelectrofocusing. The metabolism of apoA-I isoproteins was studied in normal volunteers (N = 6) in a metabolic ward. In the first study proapoA-I and mature apoA-I (apoA-I0 isoform) were injected simultaneously into two normal subjects and the conversion of proapoA-I to mature apoA-I and the decay of radioactivity were followed in plasma and HDL over a 14-day period. ProapoA-I was rapidly and completely converted to mature apoA-I with a fractional rate of conversion of 4.0 pools/day. The average residence times of proapoA-I and mature apoA-I were 0.23 and 6.5 days, respectively. The mature apoA-I derived from proapoA-I had a residence time which was the same as the injected mature apoA-I.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008196:Lymph / Q000378:metabolism; D008297:Male; D011498:Protein Precursors / Q000097:blood / Q000378:metabolism*
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; D011498:Protein Precursors