Transcript 10.2 Enzymes and Metabolic Pathways

From Proteins to Phenotypes
Chapter 10
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.
10.2 Enzymes and Metabolic Pathways
 Biochemical reactions in the cell are linked
together to form metabolic pathways
Metabolism
 Metabolism
• The sum of all biochemical reactions by which
cells convert and utilize energy
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
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
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)
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
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
Keep In Mind
 Phenylketonuria and several other metabolic
disorders can be treated by dietary restrictions
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
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-1phosphate accumulate, causing cataracts and
mental retardation
• Dietary treatment does not prevent long-term
complications
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
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
Keep In Mind
 Sickle cell anemia is caused by substitution of a
single amino acid in beta globin
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.
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.
Genetic Differences in Ability to Taste
 PROP compounds (related to PTC) in kale,
cabbage, broccoli and Brussels sprouts taste
bitter to some people
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
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.
Keep In Mind
 Small differences in proteins can have a large
effect on our ability to taste, smell, and
metabolize medicines
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