Chapter 9: Biochemical Genetics Flashcards
- The 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
Biochemical genetics
- The science concerned with the chemical and the physical nature of __ and the mechanism by which they control the development and maintenance of the organism.
- Use to define __ __.
- genes
- metabolic diseases
__ __ are conditions caused by inherited enzyme deficiencies that disrupt normal body metabolism.
Metabolic diseases (Garrod’s hypothesis)
What is Garrod’s hypothesis?
Garrod’s hypothesis (1908) proposes that metabolic diseases result from inherited enzyme deficiencies that disrupt normal body metabolism.
According to Garrod’s hypothesis, enzyme deficiencies lead to the accumulation of a __ __, which is the compound acted upon by an enzyme in a __ __. Additionally, there may be impaired formation of a product that is normally produced by the deficient enzyme.
- toxic substrate
- chemical reaction
What are the consequences of enzyme deficiencies according to Garrod’s hypothesis?
According to Garrod’s hypothesis (1908), enzyme deficiencies lead to the accumulation of a toxic substrate, which is the compound acted upon by an enzyme in a chemical reaction. Additionally, there may be impaired formation of a product that is normally produced by the deficient enzyme.
Garrod’s hypothesis was proposed by __ __ __ in __, pioneering the understanding of the genetic basis of metabolic diseases.
- Sir Archibald Garrod
- 1902
- What happens in normal metabolic pathways?
- What can occur if there is a deficiency or malfunction of an enzyme in a metabolic pathway?
- In normal metabolic pathways, enzymes catalyze the conversion of substrates into products.
- If there is a deficiency or malfunction of an enzyme involved in a particular step of a metabolic pathway, the substrate may accumulate because it cannot be converted into the product.
When an enzyme is deficient or absent, the excess substrate may be diverted into __ __ __. What can be produced as a result of this?
- alternative metabolic pathways
- toxic metabolites or by-products
Garrod’s Hypothesis proposes “__ __ - __ __,” suggesting that genes act through the production of enzymes.
one gene - one enzyme
According to Garrod’s Hypothesis, each __ is responsible for producing a single __.
- gene
- enzyme
Garrod’s Hypothesis: “One Gene-one enzyme”
Genes act through the production of __, with each gene responsible for producing a single enzyme that in
turn affects a single step in a __ __.
- enzymes
- metabolic pathway
- metabolic pathways: Highly __ __ making up the __ __ that continually occur in the body.
- Produce crucial chemicals such as __, __for the digestion of food and the breakdown of various body wastes.
- controlled sequences
- biochemical reactions
- pigments
- enzymes
- refer to the inability to produce a certain enzyme, which interrupts a metabolic pathway.
- In the homozygous recessive state, a defective enzyme in the metabolic pathway can result in serious physiological consequences.
inborn errors of metabolism
Who first observed and coined the term “inborn errors of metabolism”?
Sir Archibald Garrod observed that inherited diseases reflect a patient’s inability to make a particular enzyme, which he referred to as “inborn errors of metabolism.”
Garrod’s hypothesis was proven to be correct by __ and __ in the 1930s. They demonstrated the relationship between genes and enzymes, confirming the concept of “__ __-__ __.”
- George Beadle
- Edward Tatum
- one gene - one enzyme
Garrod studied __, a harmless but rare disorder in the general population but more frequent in children of first-cousin marriages.
alkaptonuria
What is the characteristic symptom of alkaptonuria?
A patient with this disorder produces urine that when exposed to air turns distinctively dark, because these people lack the enzyme found in normal individuals who are able to convert the reddening agent, alkapton, to another substance
How did Garrod determine the nature of alkaptonuria?
Following Mendel’s laws, Garrod concluded that alkaptonuria is a congenital disorder, not the result of a bacterial infection as was commonly thought.
How was alkaptonuria often detected in infants?
diapers of infants, particularly in the front part, due to the characteristic darkening of the urine.
Garrod found that alkaptonuria is inherited as a __ __ __ trait.
single gene recessive
characterized by the abnormal accumulation of chemicals in the urine and blood.
Inborn errors of metabolism
__ __ in metabolic pathways can be circumvented by providing nutritional supplements or other means to bypass the blocked step.
Mutant blocks
In humans, inborn errors of metabolism can be managed by supplying __ __ that are lacking, such as __ in the case of diabetes, which can be synthesized and provided to patients.
- insulin
- essential substances
How to recognize metabolic disorder: (5)
- Index of suspicion
- Family History
- History
- Physical Examination
- Laboratory Examination
- refers to the initial level of suspicion or concern regarding a particular condition or illness.
Index of suspicion
- With any full-term infant who has no antecedent maternal fever or PROM (premature rupture of the membranes)
- Sick enough to warrant a blood culture or LP, one should proceed with a few simple lab tests. What way to recognize a metabolic disorder?
Index of suspicion
Many IEMs follow an __ __ __ pattern, meaning that an affected individual inherits two copies of the mutated gene, one from each parent. Therefore, a negative family history (absence of affected individuals) does not necessarily rule out the possibility of an IEM, as carriers of the mutated gene may be asymptomatic. What way to recognize a metabolic disorder?
- autosomal recessive inheritance
- Family history
increase the likelihood of inheriting autosomal recessive disorders due to the higher probability of both parents carrying the same mutated gene (3) What way to recognize a metabolic disorder?
- Consanguinity
- Ethnicity
- Inbreeding
- Family history
Family History
__ __ deaths or __ losses in the family may indicate an underlying genetic disorder, including IEMs. Such occurrences warrant thorough investigation, including genetic testing and counseling for the family.
- Recurrent neonatal
- fetal
Maternal family history is important for __-__ __ because affected males typically inherit the X chromosome from their mothers. Thus, maternal family members are more likely to be carriers or affected by the disorder.
X-linked disorders
__ __ are caused by mutations in mitochondrial DNA (mtDNA), which is inherited exclusively from the mother.
Mitochondrial disorders
What to check to recognize metabolic disorder in Family History? (3)
- Consanguinity, ethnicity, inbreeding
- Neonatal deaths, fetal losses
- Maternal family history
Males – X-linked disorders
Mitochondrial disorders
What aspects of the patient’s history are important in recognizing metabolic disorders? (2)
- Timing of onset of symptoms
- Response to therapies
What physical examination findings may indicate a metabolic disorder? (5)
- Dysmorphism
- Odor
- Jaundice
- FTT (failure to thrive)
- Hepatomegaly (enlarged liver)
What laboratory examination is typically conducted to diagnose metabolic disorders?
Anion gap metabolic acidosis
Inborn metabolic disorders (4)
- galactosemia
- phenylketonuria (PKU)
- alkaptonuria
- albinism
- Person with genotype gg, is unable to metabolize galactose because of deficiency in enzyme Gal-1-P uridyl transferase
- Blocks a step in the reaction chain and galactose accumulates in the bloodstream.
Galactosemia
Effects of galactosemia (3)
- enlarged liver
- mental retardation
- slow growth
Therapy for galactosemia
- newly born galactosemics are given a galactose-free diet.
- Early detection is a must
- Absence of enzyme phenylalanine hydroxylase resulting in the inability to hydroxylate phynelalanine to tyrosine.
- Phenylalanine converted to phenylpyruvic acid (PPA) which is released in urine.
Phenylketonuria (PKU)
Phenylketonuria:
- Absence of enzyme __ __ resulting in the inability to hydroxylate __ to __.
- Phenylalanine converted to __ __ (__) which is released in urine.
- phenylalanine hydroxylase
- phynelalanine
- tyrosine
- phenylpyruvic acid (PPA)
Effects of phenylketonuria (PKU)
excess phenylpyruvic acid (PPA) inhibits the conversion of tryptophan to serotonin in the brain and spinal cord.
Therapy of phenylketonuria (PKU)
- Diet therapy
- Early detection is a must
- Absence of homogentisic acid oxidase activity.
- Inherited as a single gene recessive trait
Alkaptonuria
Alkaptonuria:
- Absence of __ __ __ activity.
- Inherited as a __ __ __ trait
- homogentisic acid oxidase
- single gene recessive
Effect of alkaptonuria
pigmentation called ochronosis of the ear and eyes.
Individuals afflicted with alkaptonuria secrete __ __ (also called __ or __ __ __) in urine - this compound turns black when urine stands.
- homogentisic acid
- alkapton
- 2,5 dihydrophenylacetic acid
Alkaptonuaria: Homogentisic acid also accumulates in __ __, leading to a darkening of the nose, eyes and ears.
cartilaginous tissues
the condition of alkaptonuria is associated with a type of __.
arthritis
- A hereditary disorder involving the absence or reduction of melanin; an autosomal recessive trait.
- Absence of enzyme tyrosinase needed in the production of melanin.
albinism
Albinism
* A hereditary disorder involving the absence or reduction of __; an __ __ trait.
* Absence of enzyme __ needed in the production of __.
- melanin
- autosomal recessive
- tyrosinase
- melanin
- Albinos are susceptible to __, __ __ and __.
- Allele for Albinism is favored by natural selection (sexual selection) in the two __ tribes (cultural practices)
- sunburn
- skin cancer
- blindness
- Indian
