Distinct metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein(a)

Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a). The kinetics of apo(a) and apoB-100 in plasma Lp(a) were asse...

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Published in:Metabolism, clinical and experimental Vol. 65; no. 4; pp. 381 - 390
Main Authors: Diffenderfer, Margaret R., Lamon-Fava, Stefania, Marcovina, Santica M., Barrett, P. Hugh R., Lel, Julian, Dolnikowski, Gregory G., Berglund, Lars, Schaefer, Ernst J.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01.04.2016
Subjects:
Apolipoprotein B-100 - biosynthesis
Apolipoprotein B-100 - blood
Apolipoprotein B-100 - metabolism
Apolipoproteins A - biosynthesis
Apolipoproteins A - metabolism
Dyslipidemias - blood
Endocrinology & Metabolism
Fed state
Humans
Hypertriglyceridemia
Hypertriglyceridemia - metabolism
Kinetics
Leucine - metabolism
Lipids - blood
Lipoprotein(a)
Lipoprotein(a) - biosynthesis
Lipoprotein(a) - metabolism
Male
Middle Aged
apo
PR
PAS
PS
d
PCSK9
Lp(a)
TC
IDL
Lipoprotein(a)
TG
FCR
Fed state
Hypertriglyceridemia
VLDL
KIV2
KIV1
Kinetics
CHD
GC/MS
apolipoprotein
gas chromatography/mass spectrometry
intermediate density lipoprotein ( d 1.006–1.019 g/mL)
KIV 2
KIV 1
total cholesterol
fractional catabolic rate
periodic acid Schiff's base
kringle IV 2
kringle IV 1
proprotein convertase subtilisin/kexin type 9
density
production rate
triglycerides
pool size
coronary heart disease
very low-density lipoprotein ( d < 1.006 g/mL)
lipoprotein(a)
ISSN:0026-0495, 1532-8600, 1532-8600
Online Access:Get full text
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Summary:Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a). The kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9–124.7nmol/L]. All subjects received a primed constant infusion of [5,5,5-2H3] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry. Multicompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively (P=0.04). The median Lp(a) apo(a) production rate at 0.248nmol/kg·day−1 was significantly lower than that of Lp(a) apoB-100 at 0.514nmol/kg·day−1 (P=0.03). Our data indicate that apo(a) has a plasma residence time (11days) that is more than twice as long as that of apoB-100 (4days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state.
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ISSN:0026-0495
1532-8600
1532-8600
DOI:10.1016/j.metabol.2015.10.031