Molecular approach to the study of albumin synthesis

Abstract

Although serum albumin was originally recognized and described by Ancell as early as 1837 (1 ), it has only been possible to obtain insight into the mechanism for albumin synthesis in the past 10–15 years. The purpose of this chapter is to describe methods developed recently to study albumin synthesis at the molecular level. However, since classical methods still have more clinical relevance, we would like to mention briefly some of these approaches. Initial studies were devoted to the simple measurement of serum albumin levels in normal individuals and patients with various disorders and Dr. Majoor made a number of significant contributions in this area (2). Subsequently, a variety of radioactive labeling procedures were developed which permitted determination of the serum half-life (T1/2) for this protein (3). This involved intravenous injection of tracer doses of radioactive labeled albumin into patients with hypoalbuminenia and determination of the radioactive decay curve for injected material. Assuming that synthesis of albumin is equivalent to its rate of loss or degradation and that the serum pool is at steady state, a rate for albumin synthesis can be calculated indirectly from the serum decay curve (4). The next major advance in studying albumin synthesis was the development by McFarlane and colleagues of a method to measure albumin synthesis rate directly in whole animals. As these investigators recognized, there was a direct correlation between incorporation of arginine into albumin and urea synthesis, and measurement of labelled arginine in albumin after injection of 14C carbonate versus urea production could be used to calculate albumin synthesis (5). Techniques were then advanced to permit studies of albumin synthesis in the isolated—perfused liver (6), and this model has provided us with much useful information on factors involved in the regulation of albumin synthesis. These topics will be explored in depth in subsequent chapters.