High Density Lipoprotein Metabolism in a Patient with Abetalipoproteinemia

Abstract

The concentration of individual plasma apoproteins together with the in vivo metabolism of ¹²⁵I-labelled high density lipoprotein was studied in an adult male patient with abetalipoproteinemia. Plasma concentrations of cholesterol (26 mg/dl) and triglyceride (5 mg/dl) were markedly reduced and apoprotein B was absent. The concentrations of apo AI, apo All, CI, CII, Oiland E were also lower than in normal subjects. To further evaluate these changes we studied the in vivo metabolism of autologous ¹²⁵I-labelled HDL over a period of 13 days. The plasma half-life (4.1 days) and fractional catabolic rate (0.23) were similar to previously reported values for normal subjects, but overall synthesis of apoproteins AI (5.7 mg/kg/day) and All (3.6 mg/kg/day) were significantly reduced. After separation of delipidated HDL apoproteins by polyacrylamide-gel electrophoresis we were unable to demonstrate any differences in the half-life or fractional catabolic rates of apoproteins AI and All and CII plus OIL We conclude that the low concentrations of apoproteins AI and All in the plasma of our patient with abetalipoproteinemia are a consequence of reduced synthesis and do not reflect enhanced catabolism.

Regulation of low density lipoprotein receptors by plasma lipoproteins from patients with abetalipoproteinemia.

“…The lipoprotein particles present in the HDL fraction of abetalipoproteinemic plasma have an unusual density distribution, with an HDL2 to HDL3 ratio of 3:1 (29)(30)(31)(32). Although the apoprotein composition of HDL has not been fully characterized, two distinctive features appear to be a virtual absence of apoprotein GIll-1 (29,31,32) and a relative enrichment in apoprotein E (32-34, §).…”

“…Although the apoprotein composition of HDL has not been fully characterized, two distinctive features appear to be a virtual absence of apoprotein GIll-1 (29,31,32) and a relative enrichment in apoprotein E (32-34, §). Blum et al (33) Receptor-mediated uptake of LDL has been shown to be of greatest importance in tissues that actively synthesize and secrete steroid hormones (36)(37)(38): If the HDL2 particles present in the plasma of patients with abetalipoproteinemia are able to fully substitute for LDL, then it would be anticipated that maximal rates of steroid hormone production would be normal in these patients.…”

The Role of the Microsomal Triglygeride Transfer Protein in Abetalipoproteinemia

“…Kinetic studies in vivo show that the decrease in plasma ApoAI results both from a decrease in production and normal or increased catabolism (91,173). A major characteristic of the HDL of ABL patients is their enrichment in ApoE [twice as much as normal (25,45,91,94)], allowing the plasma levels of ApoE to remain normal or even slightly increased in ABL (25,173). The in vivo rate of production is equivalent to that in normal subjects (91).…”

“…ApoAIV mRNA levels and the synthesis of ApoAIV are ∼50% of normal in the enterocytes. Only the hypersialylated forms of ApoE and ApoCIII (29,37,62,71,94,118,169) are present in the plasma, and the isoform pattern of ApoAII is altered (29). Only the hypersialylated forms of ApoE and ApoCIII (29,37,62,71,94,118,169) are present in the plasma, and the isoform pattern of ApoAII is altered (29).…”

“…Although, in normal adult subjects, HDL are principally engaged in reverse C transport to the liver, the HDL of the ABL patients may assure forward C transport and thus substitute functionally for LDL (25,93,94,99). It has been estimated that ApoE-enriched HDL have the capacity to deliver to tissues, via the LDL receptor, an amount of C corresponding to a plasma LDL concentration of 50-150 mg/dl (25).…”