Chapter 9 - Biochemical Genetics Flashcards
- science concerned with the chemical and the physical nature of genes and the mechanism by which they control the development and maintenance of the organism
- use to define metabolic diseases
biochemical genetics
where is biochemical genetics used
define metabolic diseases
- an inherited enzyme deficiency leading to the disruption of normal body metabolism
- accumulation of a toxic substrate
- impaired formation of a product normally produced by the deficient enzyme
Metabolic disease
compound acted upon by an enzyme in a chemical reaction
substrate
Archibald Garrod’s Hypothesis
one gene - one enzyme
Genes act through the production of enzymes, with each gene responsble for producing a single enzyme that in turn affects a single step in a metabolic pathway
Archibald Garrod’s Hypothesis
- highly contrlled sequences making up the biochemical reactions that continually occur in the body
- produce crucial chemicals such as pigments, enzymes for the digestion of food and the breakdown of various body wastes
metabolic pathways
inability to produce a certain enzyme, thus interrupting a metabolic pathway
inborn errors of metabolism
what is the result of homozygous recessive state on metabolic pathways
serious physiological consequences
what did Garrod reffer to inherited diseases that reflect a patient’s inability to make a particular enzyme
inborn errors of metabolism
who proved Garrod’s hypothesis
- Beadle
- Tatum
when did Archibald Garrod propose the relationship between genes and proteins
1908
what disease did Archibald Garrod study
Alkaptonuria
where is Alkaptonuria common
children of first-cousin marriages
- a patient with this disorder produces urine that when exposed to air turns distinctively dark
- these people lack the enzyme found in normal individuals who are able to convert the reddening agent to another substance
Alkaptonuria
How to recognize metabolic disorder
- index of suspicion
- family history
- history
- physical examination
- laboratory examination
history
- timing of onset of symptoms
- response to therapies
- unable to metabolize galactose because of deficiency in enzyme Gal-1-Puridyl transferase
- person with genotype gg
- blocks a step in the reaction chain and galactose accumulates in the bloodstream
Galactosemia
what is deficient in people with Galactosemia
Galactose-1-Phosphate Uridyltransferase
Effects of Galactosemia
- enlarged liver
- mental retardation
- slow growth
Therapy of people with Galactosemia
newly born is given galactose-free diet
what is a must in people with Galactosemia
early detection
What is damaged in people with Galactosemia
- liver
- eyes
- kidneys
- brain
- absence of enzyme phenylalanine hydroxylase
- resulting in inability to hydroxylate phennylalanine to tyrosine
- phenylalanine converted to phenylpyruvic acid (PPA) which is released in urine
Phenylketonuria (PKU)
what enzyme is absent in people with Phenylketonuria (PKU)
phenylalanine hydroxylase
PPA
phenylpyruvic acid
Effects of Phenylketonuria (PKU)
excess PPA inhibits conversion of tryptophan to serotonin in brain and spinal cord
Therapy for Phenylketonuria (PKU)
diet therapy
- absence of homogentisic acid oxidase activity
- inherited as a single gene recessive trait
- causes pigmentation called ochronsois of the ear and eyes
Alkaptonuria
what enzyme is absent in people with Alkaptonuria
homogentisate 1,2-dioxygenase
what activity is absent in people with Alkaptonuria
homogentisic acid oxidase activity
where does homogentisic acid also accumulate
cartilaginous tissues
bluish-black discoloration of certain tissues, such as the ear
ochronosis
Homogentisic acid accumulation leads to darkening of what?
- nose
- eyes
- ears
what is the effect of Alkaptonuria in the joints
benign arthritis
- absence or reduciton or melanin
- autosomal recessive trait
- absence of enzyme tyrosinase needed in the production of melanin
albinism
what enzyme is absent in albino people
tyrosinase
