Feedback and Feedforward Phenomena

The role of the end products of a metabolic pathway in regulating their own biosynthesis was first demonstrated by Roberts et al. (1955). Working with E. co/z, they showed that amino acid synthesis from glucose is inhibited by the addition of amino acids to the incubation medium. Umbarger (1956) demonstrated that end products may inhibit the activity of enzymes mediating end-product synthesis. Often this inhibition is exerted on the first enzyme of the metabolic sequence. End products may also inhibit enzyme synthesis itself, as is frequently observed in anabolic pathways for amino acids, purines, and pyrimidines. This latter mode of metabolic regulation is termed repression and may occur independently of feedback inhibition. Both mechanisms may be involved in regulation of the same biosynthetic pathway. However, unlike feedback inhibition, which provides very rapid control, repression is a relatively slow process which permits adjustment of metabolism over an extended period of time. 

Feedback inhibition has been studied most closely in microbial systems and has been reviewed by Stadtman (1966, 1970). Servome- 

In the following pages we will describe the role of servomechanisms in modulating the activity of three key pathways of mammalian metabolism glycolysis, fatty acid synthesis, and cholesterol synthesis. The regulation of each sequence depends upon a constant flow of information to key enzymes and receptors. A defect of function of any single component could be a cause of disease. 

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