From Proteins to Phenotypes

1. From Proteins to Phenotypes Chapter 10

2. 10.1 Proteins Are the Link Between Genes and the Phenotype • Proteins are the visible end product of the gene expression pathway • Some genes encode proteins that act as growth hormones, receptors, and growth factors • Other genes encode proteins that act as biological catalyst called enzymes.

3. 10.2 Enzymes and Metabolic Pathways • Biochemical reactions in the cell are linked together to form metabolic pathways

4. Metabolism • Metabolism • The sum of all biochemical reactions by which cells convert and utilize energy

5. 10.3 Phenylketonuria (PKU): A Mutation That Affects an Enzyme • Phenylalanine is an essential amino acid and the starting point for a network of metabolic reactions • Essential amino acids • Amino acids that cannot be synthesized in the body and must be supplied in the diet

6. Phenylalanine Metabolism and PKU • A mutation in a gene encoding the enzyme, phenalanine, that controls the first step in the breakdown of phenylalanine causes phenylketonuria (PKU). • PKU affects about 1 in every 12,000 newborns

7. PKU • Phenylketonuria (PKU) • An autosomal recessive disorder of amino acid metabolism that results in mental retardation if untreated • The phenotype is caused by the buildup of phenylalanine and the products of secondary reactions (such as phenylpyruvic acid)

8. PKU Can Be Treated With Diet • Infants with PKU can develop normally before birth, then develop neurological damage when fed a diet containing protein • A PKU diet must contain phenylalanine levels high enough for normal development, but low enough to prevent mental retardation

9. Genetic Journeys: Dietary Management and Metabolic Disorders • For PKU, a formula is prepared from enzymatically digested proteins (or synthetic mixtures of amino acids), fats, carbohydrates, and vitamin and mineral supplements • A typical lunch might include vegetable soup, crackers, fruit cocktail, and formula

10. Keep In Mind • Phenylketonuria and several other metabolic disorders can be treated by dietary restrictions

11. 10.5 Genes and Enzymes of Carbohydrate Metabolism • Mutations in genes encoding enzymes can affect the metabolic pathways of other biological molecules, including carbohydrates • Galactosemia is a genetic disorder caused by lack of an enzyme in sugar metabolism

12. Galactosemia is Caused by Enzyme Deficiency • Galactosemia • A heritable trait associated with the inability to metabolize the sugar galactose • If left untreated, high levels of galactose-1-phosphate accumulate, causing cataracts and mental retardation • Dietary treatment does not prevent long-term complications

13. Studies of Sickle Cell Anemia • Sickle cell anemia was the first example of inherited variation in protein structure • First direct proof that mutations result in a change in amino acid sequence in proteins • Evidence that a change in a single nucleotide can cause a genetic disorder

14. Genetic Journeys:The First Molecular Disease • Studies by Linus Pauling and James Neel concluded that a mutant gene involved in the synthesis of hemoglobin causes sickle cell anemia, and that a genetic disorder can be caused by a defect in a single molecule

15. Keep In Mind • Sickle cell anemia is caused by substitution of a single amino acid in beta globin

16. 10.8 Pharmacogenetics • Individual differences in reactions to therapeutic drugs represent a “hidden” set of phenotypes that are not revealed until exposure occurs • The first pharmacogenetic trait was discovered in the 1930s when researchers at DuPont were trying to develop a sugar substitute.

17. Pharmacogenetics • Pharmacogenetics • A branch of genetics concerned with inheritance of differences in the response to drugs • Variations in the amino acid sequences of proteins affect the way individuals react to prescription drugs and chemicals in the environment • For example, why some people can smoke for cigarettes for years & never develop lung cancer.

18. Genetic Differences in Ability to Taste • PROP compounds (related to PTC) in kale, cabbage, broccoli and Brussels sprouts taste bitter to some people

19. Genetic Differences in Ability to Smell • Two-thirds of people tested could smell pink Verbena flowers but not red ones; the rest could smell red flowers but not pink ones

20. Drug Sensitivities are Genetic Traits • Gene variations and breast cancer therapy • Cancer center treatment facilities are sequencing the genome of tumors to design treatments for their patients.

21. Keep In Mind • Small differences in proteins can have a large effect on our ability to taste, smell, and metabolize medicines

22. 10.9 Ecogenetics • Ecogenetics • The study of genetic variation that affects responses to environmental chemicals • Some individuals may be sensitive or resistant to environmental chemicals such as pesticides • Important in research, medicine, and public policy