Explain how 2 different types of mutations in a gene can result in the loss of an enzyme's function

The primary structure of a protein is determined by the sequence of amino acids in the polypeptide chain. This amino acid sequence is directly coded for by the sequence of codons in the mRNA. As the mRNA is synthesised by complementary base pairing of RNA nucleotides with the enzyme's gene (catalysed by RNA polymerase II in eukaryotes), a mutation in the DNA sequence will cause a change to the mRNA sequence. If this was a point mutation, a single codon in the mRNA would be affected so one amino acid in the polypeptide chain would be changed. However, if this was a frameshift mutation (insertion/deletion of a base), all subsequent codons would be affected. Therefore, all the amino acids in the polypeptide chain would be different to the wild type protein. The folding of the polypeptide chain by hydrogen bonding to form the secondary structure (e.g. alpha helices and beta pleated sheets) is dependent on the sequence of residues in the primary structure. As a result, a change to this sequence caused by a mutation will change the secondary structure. This will also mean that the ionic interactions, disulfide bridges and further hydrogen bonding that occurs between R groups of the residues will not be that required to form the correct 3D structure found in the wild type enzyme. Furthermore, the hydrophobic effect will cause a different 3D structure as the hydrophilic and hydrophobic side chains will not be in the appropriate places (for frameshift mutation). As the function of the enzyme is dependent on its 3d structure (e.g. active site must be able to bind substrate), the changes to the final enzyme structure described due to a mutation will cause a loss of function (which for an enzyme is catalysis).