Some metabolic processes are readily understood because they are circumscribed in metabolic pathways that have clearly identifiable beginning points, end products, and other features. Other metabolic pathways that do not appear to be straightforward pose difficulties for students. One such metabolic process, the purine nucleotide cycle, is discussed here.Keywords: AMP deaminase, ammonia, branched-chain amino acids, glutamine.Understanding metabolism requires considerable integrative capability by the teacher and/or the student because metabolic events in one pathway are often related to events in other pathways. Whereas students of biochemistry have appreciable understanding of such metabolic pathways as glycolysis, gluconeogenesis, and lipogenesis, other equally important metabolic processes are not so straightforward and not readily understood. Two examples are the purine nucleotide cycle and metabolism of the one-carbon moieties, the so-called "one-carbon pool." Teachers often have a difficult task presenting these topics to students presumably because in textbooks of biochemistry they are usually discussed in multiple settings and in multiple chapters that are designed for other purposes. A discussion of any metabolic pathway should expose the potential biological role of the pathway in a manner that makes the subject simple but does not leave too many loose ends. The intent of this two-part series is to facilitate teaching and learning of the metabolic interactions involved in these two distinct and apparently complex areas of metabolism. It is not intended to be a comprehensive review of these metabolic processes. The reader should consult other sources for topics dealing with regulation of these metabolic processes. Here, I discuss the purine nucleotide cycle; in the accompanying article [1], I discuss metabolic processes germane to the one-carbon pool.
METABOLIC IMPORTANCE OF THE PURINE NUCLEOTIDE CYCLE IN MUSCLEThe hydrolysis of ATP to ADP is high during muscle activity. Exercising muscle produces considerable amounts of ammonia from the deamination of AMP formed in the process of regenerating ATP from ADP through the adenylate kinase (myokinase) reaction (2ADP 7 ATP ϩ AMP). As will be discussed later in this article, AMP deaminase is one of the three enzymes that makes up the purine nucleotide cycle. The major metabolic role of this cycle is to provide ammonia for the synthesis of glutamine, which is then exported to the kidney, where its catabolism generates ammonia that is used to neutralize the acidity of the tubular urine. Ammoniagenesis in the kidney is a very important metabolic process during fasting or starvation. The synthesis of glutamine in muscle is thus a critical response to starvation, and the purine nucleotide cycle is a central player in this process.
REACTIONS OF THE PURINE NUCLEOTIDE CYCLEThe purine nucleotide cycle is a cyclic sequence of biochemical reactions that funnels the amino group of aspartate into a purine nucleotide (IMP) to generate adenylosuccinate, which is broken down ...