Synthesis of plasma antihaemophilic factor.

Abstract

IN Nature of May 12, 1962, L. I. Woolf offered an explanation of ‘severe’ and ‘mild’ X-linked haemophilia A while discussing gene expression in heterozygotes. He proposed that the plasma-level of antihaemophilic globulin (AHG, AHF, Factor VIII) regulated its rate of synthesis, that is, that ‘end-product (feedback) inhibition’ controlled the synthetic rate. ‘Feedback inhibition’ is known to be a very important regulatory mechanism in biosynthetic pathways, producing small anabolites such as amino-acids, vitamins, etc.1. We can find no documented evidence, however, that ‘feedback inhibition’ is a controlling mechanism in protein synthesis. ‘Feedback inhibition’ should be sharply distinguished in this respect from ‘feedback repression’, which is recognized to be a highly important genetic mechanism concerned with regulating the synthesis of enzymes (proteins) in bacteria1–4.