Proteins can be classified into two broad types:

Active proteins - enzymes, the biological catalysts that make possible the thousands of chemical reactions that go on inside a living cell. - microtubule proteins that produce movement in the cell - membrane-bound proteins that regulate pumping of ions and nutrients across the membrane. Structural proteins - contribute to the structural properties of the cell and the organism; human hair keratin and bone collagen are two structural proteins. Some proteins are both active and structural, for example, the contractile proteins actin and myosin, which comprise the great bulk of muscles and hence affect shape.

Enzyme Function
Active sites

Enzymes are biological catalysts that speed up chemical reactions that otherwise would occur too slowly for cells to function. The substrate molecules fit into an enzyme's active site. Enzymes do their job of catalysis by physically grappling with the substrate molecules, interacting with them to make or break chemical bonds.

Schematic representation of the action of a hypothetical enzyme in putting two substrate molecules together
(a) In the "lock-and-key" mechanism the substrates have a complementary fit to the enzyme's active site. (b) In the induced-fit model, binding of substrates induces a conformational change in the enzyme. (c) Enzymes are highly specific for the chemical reactions they catalyze, and the specificity lies in the precise fit between substrate and active site.

Malfunctioning Alleles

In genetics the standard organismal phenotype is called the wild-type, because this is the type observed in the wild, in other words, in nature. All essential genes must be capable of producing their functional products in order to produce this wild-type phenotype. These normally functioning alleles are called wild-type alleles.

Mutations (changes in the DNA sequence of a gene, occur

spontaneously in nature). Since alleles are forms of genes, mutations by definition create new alleles. In genetic research, a gene is generally symbolized by a letter or several letters based on the word describing the phenotype produced by a mutant allele. Then the corresponding wild-type allele is designated by the addition of a superscript plus sign (+). For example the wild-type eye color of the fruit fly Drosophila is red, but a mutant allele of a gene on the X-chromosome produces white eyes, so the mutant allele is designated w and its wild-type allele is w +.

Genetic disease

A common cause of genetic disease in humans is enzyme deficiency caused by mutation. Human cells carry two chromosome sets, so all genes are represented twice (gene pairs). Normally both are wild-type alleles. However, individuals carrying a pair of defective alleles of a gene coding for an enzyme will show reduced or no enzyme activity and express disease symptoms.

Mutations can lead to gene malfunction by changes in sequences that are protein-coding or important for information processing.

Gene Mutation

MISSENSE MUTATION In this example, the nucleotide adenine is replaced by cytosine in the genetic code, introducing an incorrect amino acid into the protein sequence.

Gene Mutation

NONSENSE MUTATION In this example, the nucleotide cytosine is replaced by thymine in the DNA code, signaling the cell to shorten the protein.

Gene Mutation

INSERTION MUTATION In this example, one nucleotide (adenine) is added in the DNA code, changing the amino acid sequence that follows.

Gene Mutation

DELETION MUTATION In this example, one nucleotide (adenine) is deleted from the DNA code, changing the amino acid sequence that follows.

Gene Mutation

FRAMESHIFT MUTATION A frameshift mutation changes the amino acid sequence from the site of the mutation.

Gene Mutation

REPEAT EXPANSION MUTATION In this example, a repeated trinucleotide sequence (CAG) adds a series of the amino acid glutamine to the resulting protein.

Effects of mutations on cellular function

Generally, mutations result in reduced protein function or no protein function. A mutation with reduced function is called a leaky mutation because some of the wild-type function "leaks" through into the phenotype. A mutation that results in no protein function is called a null mutation. Changes that do not affect the function of a protein are called silent mutations.

Positions of mutant sites and their functional consequences

Some mutations alter the informationtransfer process rather than directly altering the genetic code. Some mutations produce malfunction not through any effect on amino acid sequence but on intron splicing. Since intron splicing depends on specific nucleotide sequences at the exon-intron boundaries and inside the intron, if these sites are mutated, the intron cannot be excised and no functional mRNA will be produced. A similar mutation alters the regulation of the gene. For example, the promoter sequence to which the RNA polymerase binds is crucial, and if changes occur in this sequence, the gene might not be transcribed at all or might be transcribed at abnormally low (or high) rates.

Enzyme Failures. One small part of the human metabolic map, showing the
consequences of various specific enzyme failures.

(After I. M. Lerner and W. J. Libby, Heredity, Evolution, and Society, 2d ed. Copyright 1976 by W. H. Freeman and Company.)

Phenylketonuria (PKU)

A defect in the enzyme phenylalanine hydroxylase causes a buildup of phenylalanine (originating from dietary protein). At high concentrations phenylalanine is converted into phenylpyruvic acid, a substance that interferes with the development of the nervous system, giving rise to mental retardation in an infant with two copies of the defective allele. If the high level of phenylpyruvic acid is detected soon after birth, the baby can be placed on a special lowphenylalanine diet and develops without retardation.

Cystic Fibrosis

The most commonly found mutation is a deletion of three nucleotides, which should result in the removal of the amino acid phenylalanine from the primary sequence of the protein.

The location of the cystic fibrosis gene on chromosome 7, with an enlargement showing the nature of the common 3-bp deletion that removes a phenylalanine from the polypeptide sequence.

Cystic Fibrosis

This is not caused by an enzyme deficiency but by inactivity of a protein that controls the passage of chloride ions through membranes in secretory tissue.