1. Chapter 4 – proteins, mutations & genetic disorders
Unit 1 – Human Cells

2. Protein Structure Proteins all contain 4 chemical elements:
- carbon (C)
- oxygen(O)
- hydrogen (H)
- nitrogen (N)
Proteins are made up of subunits called amino acids
- approximately 20 different types
Protein length is very variable

3. Polypeptides Amino acids join together
- with links called peptide bonds
Chains of amino acids are called polypeptides
During protein synthesis, amino acids are joined in a specific order
This determines their ultimate structure and function

4. Protein bonding Several types of bonds link amino acids together
Hydrogen bonds:
- form between amino acids
- cause the protein chain to fold or coil
Further linkages:
- bridges between sulphur atoms
- attractions between positive or negative atoms
All bonds help form the overall 3-D structure
- vital in determining it’s function

5. Final protein structure varies greatly
- depends on how polypeptide chains become arranged

6. Types of protein

7. Functions of protein Enzymes: - speed up biochemical reactions
- proteins are folded to expose an active site
- this combines with a specific substrate
Structural:
- key component of cellular membranes
- muscular contraction
Hormones:
- chemical messengers to certain target tissues
E.g. insulin, ADH, growth hormone
Antibodies:
- defend the body against antigens
Associations with other chemicals:
- can form glycoproteins
- haemoglobin

8. Mutation
A change in the structure or composition of an organisms genome
An individual with a mutation affecting their phenotype is called a mutant
Mutations arise spontaneously, at random, and are rare
Mutation rates can be increased by certain mutagenic agents
E.g. mustard gas, radiation
- these mutations are said to be induced

9. Mutations & Genetic Disorders
Mutations can alter genes or entire chromosomes
Therefore, proteins produced don’t function correctly
- or aren’t produced at all
This is the cause of genetic disorders
- many of which are disabling or even lethal

10. Single-gene mutation – Point mutation
A change in one nucleotide in the DNA of a single gene
Three types:
-substitution
- deletion
- insertion

11. Single-gene mutation – splice site
mRNA contains both coding and non-coding regions
- non-coding regions (INTRONS) need to be removed
- remaining coding regions (EXONS) are then joined together
- this process is called splicing
If mutation occurs at a splice site, introns may be retained in error

12. Single-gene mutation – nucleotide sequence repeat expansion
Insertion of copies of one triplet sequence
- often the triplet can be repeated several hundred times

13. Impacts of mutation on protein structure
Missense:
- a substitution causes a single codon to be changed
- amino acid produced, but not the original one intended
E.g. sickle-cell anaemia, PKU
Nonsense:
- after substitution, codon is changed to a stop codon
- protein synthesis stops
- polypeptide chain shorter than normal
- unable to function
E.g. Duchenne muscular dystrophy

14. Impacts of mutation on protein structure
Splice-site mutation:
Retaining introns leads to an altered protein
Protein won’t function properly
E.g. beta thalassemia
Frameshift:
- follow insertion or deletion
- all codons after mutation are shifted out of frame
- protein usually non functional
E.g. cystic fibrosis, Tay-Sachs
Nucleotide sequence repeat expansion
- defective protein has many repeats of an amino acid
- sometimes protein not formed at all (silenced)
E.g. Huntington’s, fragile X syndrome

15. Chromosome structure mutations
Caused by chromosomes breaking apart
- forms “sticky” ends which can join other broken ends
Deletion:
- results in chromosome lacking genes
- normally drastic effects
E.g. Cri-du-chat syndrome
Duplication:
- when deleted segments of genes attach to a partner chromosome
- a set of genes is therefore repeated
E.g. common in some cancers

16. Chromosome structure mutations
Translocation:
- section of chromosome breaking off and attaching to a non-matching partner
2 types:
Non-reciprocal
Reciprocal
Common in cancers
E.g. chronic myeloid leukaemia
Or, can significantly alter phenotype
E.g. Down’s Syndrome