Inborn errors of metabolism disorders in which there

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Unformatted text preview: ns • How do we know that proteins are the readout of genetic expression? • Inborn Errors of Metabolism: Disorders in which there is a clear metabolic (enzymatic) defect, and which are heritable (genetic) • Examples: Alkaptonuria and Phenylketonuria (both are defects in the metabolism of specific amino acids) • This led to the one-gene, one enzyme hypothesis: One Gene: One Enzyme • George Beadle (1933) – Working with induced metabolic mutations in Neurospora crassa – Generated mutations on “complete” media, then tested growth on “minimal” media One Gene: One Enzyme X-rays Amino acids nucleotides Complete medium Vitamins Minimal medium • Each mutation seemed to lead to the loss of an essential enzymatic function • All major biochemical pathways could be affected Genetic Analysis of Biochemical Pathways • Adrian Srb and Nathan Horowitz - arginine biosynthesis in Neurospora • 7 mutant strains: – None grew on minimal medium – All grew on minimal medium plus arginine • Tested each mutant for growth on citrulline and ornithine (chemically quite similar to arginine) Genetic Analysis of Biochemical Pathways • 4 mutants (arg4-arg7) grew on both cit and orn, in addition to arg • 2 mutants (arg2 and arg3) grew on cit (and arg), but not orn • arg1...
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