Apolipoproteins: metabolic role and clinical biochemistry applications

Abstract

Lipoprotein metabolism is dependent on apolipoproteins, multifunctional proteins that serve as templates for the assembly of lipoprotein particles, maintain their structure and direct their metabolism through binding to membrane receptors and regulation of enzyme activity. The three principal functions of lipoproteins are contribution to interorgan fuel (triglyceride) distribution (by means of the fuel transport pathway), to the maintenance of the extracellular cholesterol pool (by means of the overflow pathway) and reverse cholesterol transport. The most important clinical application of apolipoprotein measurements in the plasma is in the assessment of cardiovascular risk. Concentrations of apolipoprotein B and apolipoprotein AI (and their ratio) seem to be better markers of cardiovascular risk than conventional markers such as total cholesterol and LDL-cholesterol. Apolipoprotein measurements are also better standardized than the conventional tests. We suggest that measurements of apolipoprotein AI and apolipoprotein B are included as a part of the specialist lipid profile. We also suggest that lipoprotein (a) should be measured as part of the initial assessment of dyslipidaemias because of its consistent association with cardiovascular risk. Genotyping of apolipoprotein E isoforms remains useful in the investigation of mixed dyslipidaemias. Lastly, the role of postprandial metabolism is increasingly recognized in the context of atherogenesis, obesity and diabetes. This requires better markers of chylomicrons, very-low-density lipoproteins and remnant particles. Measurements of apolipoprotein B48 and remnant lipoprotein cholesterol are currently the key tests in this emerging field.