Even the simplest cell may house thousands of individual chemical reactions. But the number of different kinds of chemical reaction is surprisingly small. In fact, we saw the same underlying pattern in our discussion of genetic regulation. While the specific details of the vast array of regulatory events may be complicated, only a fairly small number of different principles are needed to explain the essential mechanisms at work in an organism. There is often a surprising degree of simplicity underlying the seemingly complex events of life. As we will see in this chapter, the genetic control of metabolism is no different. But we can never lose sight of the fact that it is the understanding of the specific processes, in all their complexity, that actually makes the difference for an individual patient.
The study of metabolism focuses on function. Metabolism is made up of the biochemical reactions with which a living system obtains energy from the environment and stores it or uses it for growth and other biological activity. As we saw in Chapter 2, the study of so-called "inborn errors of metabolism" gave Garrod and other early researchers their first insight into how our genetic makeup controls life processes. One of the earliest recognized human metabolic diseases, phenylketonuria (PKU; Figure 8-1), provides a good prototype of the way our current understanding of the genetic control of metabolism is applied in practice.
Adult male with PKU. This patient was born before the advent of newborn screening. His diagnosis was not made until he was 23 years old. He has severe cognitive impairments.
The recessive condition PKU was first described in 1934 by A. Fölling, based on his study of two siblings. This brother and sister showed mental retardation. They also had a characteristic musty odor to their urine, where Fölling discovered phenylpyruvic acid. A special diet low in phenylalanine, adopted in 1955, was the first effective therapy for this condition. Soon after that, a blood screening test was developed, and states began to adopt laws requiring newborn children to be tested before they were discharged from hospitals. Today, about 300 newborn children are diagnosed with PKU each year, and mental retardation is prevented by early implementation of a low-phenylalanine diet. As microarrays and other biochemical assays enter the field, designing better-tailored treatment regimens can benefit future patients. But few will probably be as directly treatable as this dietary approach to a comparatively simple metabolic disorder.
As we learn more about individual metabolic disorders, the conditions that were once grouped together as examples of the same defect are often found to be functionally related but biochemically separable. After all, metabolism is a sequential process of reaction steps toward a shared outcome. But even when the underlying biochemistry is well-understood, the treatment regimen may not ...