Chapter 9: Biochemical Genetics

Question 1

• 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.

Answer 1

Biochemical genetics

Question 2

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 __ __.

Answer 2

• genes
• metabolic diseases

Question 3

__ __ are conditions caused by inherited enzyme deficiencies that disrupt normal body metabolism.

Answer 3

Metabolic diseases (Garrod’s hypothesis)

Question 4

What is Garrod’s hypothesis?

Answer 4

Garrod’s hypothesis (1908) proposes that metabolic diseases result from inherited enzyme deficiencies that disrupt normal body metabolism.

Question 5

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.

Answer 5

• toxic substrate
• chemical reaction

Question 6

What are the consequences of enzyme deficiencies according to Garrod’s hypothesis?

Answer 6

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.

Question 7

Garrod’s hypothesis was proposed by __ __ __ in __, pioneering the understanding of the genetic basis of metabolic diseases.

Answer 7

• Sir Archibald Garrod
• 1902

Question 8

• What happens in normal metabolic pathways?
• What can occur if there is a deficiency or malfunction of an enzyme in a metabolic pathway?

Answer 8

• 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.

Question 9

When an enzyme is deficient or absent, the excess substrate may be diverted into __ __ __. What can be produced as a result of this?

Answer 9

• alternative metabolic pathways
• toxic metabolites or by-products

Question 10

Garrod’s Hypothesis proposes “__ __ - __ __,” suggesting that genes act through the production of enzymes.

Answer 10

one gene - one enzyme

Question 11

According to Garrod’s Hypothesis, each __ is responsible for producing a single __.

Answer 11

• gene
• enzyme

Question 12

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 __ __.

Answer 12

• enzymes
• metabolic pathway

Question 13

• 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.

Answer 13

• controlled sequences
• biochemical reactions
• pigments
• enzymes

Question 14

• 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.

Answer 14

inborn errors of metabolism

Question 15

Who first observed and coined the term “inborn errors of metabolism”?

Answer 15

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.”

Question 16

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 “__ __-__ __.”

Answer 16

• George Beadle
• Edward Tatum
• one gene - one enzyme

Question 17

Garrod studied __, a harmless but rare disorder in the general population but more frequent in children of first-cousin marriages.

Answer 17

alkaptonuria

Question 18

What is the characteristic symptom of alkaptonuria?

Answer 18

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

Question 19

How did Garrod determine the nature of alkaptonuria?

Answer 19

Following Mendel’s laws, Garrod concluded that alkaptonuria is a congenital disorder, not the result of a bacterial infection as was commonly thought.

Question 20

How was alkaptonuria often detected in infants?

Answer 20

diapers of infants, particularly in the front part, due to the characteristic darkening of the urine.

Question 21

Garrod found that alkaptonuria is inherited as a __ __ __ trait.

Answer 21

single gene recessive

Question 22

characterized by the abnormal accumulation of chemicals in the urine and blood.

Answer 22

Inborn errors of metabolism

Question 23

__ __ in metabolic pathways can be circumvented by providing nutritional supplements or other means to bypass the blocked step.

Answer 23

Mutant blocks

Question 24

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.

Answer 24

• insulin
• essential substances

Question 25

How to recognize metabolic disorder: (5)

Answer 25

* Index of suspicion * Family History * History * Physical Examination * Laboratory Examination

Question 26

- refers to the initial level of suspicion or concern regarding a particular condition or illness.

Answer 26

Index of suspicion

Question 27

- 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?

Answer 27

Index of suspicion

Question 28

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?

Answer 28

- autosomal recessive inheritance - Family history

Question 29

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?

Answer 29

- Consanguinity - Ethnicity - Inbreeding - Family history

Question 30

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.

Answer 30

- Recurrent neonatal - fetal

Question 31

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.

Answer 31

X-linked disorders

Question 32

__ __ are caused by mutations in mitochondrial DNA (mtDNA), which is inherited exclusively from the mother.

Answer 32

Mitochondrial disorders

Question 33

What to check to recognize metabolic disorder in Family History? (3)

Answer 33

- Consanguinity, ethnicity, inbreeding - Neonatal deaths, fetal losses - Maternal family history – Males – X-linked disorders – Mitochondrial disorders

Question 34

What aspects of the patient's history are important in recognizing metabolic disorders? (2)

Answer 34

- Timing of onset of symptoms - Response to therapies

Question 35

What physical examination findings may indicate a metabolic disorder? (5)

Answer 35

- Dysmorphism - Odor - Jaundice - FTT (failure to thrive) - Hepatomegaly (enlarged liver)

Question 36

What laboratory examination is typically conducted to diagnose metabolic disorders?

Answer 36

Anion gap metabolic acidosis

Question 37

Inborn metabolic disorders (4)

Answer 37

- galactosemia - phenylketonuria (PKU) - alkaptonuria - albinism

Question 38

* 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.

Answer 38

Galactosemia

Question 39

Effects of galactosemia (3)

Answer 39

- enlarged liver - mental retardation - slow growth

Question 40

Therapy for galactosemia

Answer 40

- newly born galactosemics are given a galactose-free diet. - Early detection is a must

Question 41

- 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.

Answer 41

Phenylketonuria (PKU)

Question 42

Phenylketonuria: - Absence of enzyme __ __ resulting in the inability to hydroxylate __ to __. - Phenylalanine converted to __ __ (__) which is released in urine.

Answer 42

- phenylalanine hydroxylase - phynelalanine - tyrosine - phenylpyruvic acid (PPA)

Question 43

Effects of phenylketonuria (PKU)

Answer 43

excess phenylpyruvic acid (PPA) inhibits the conversion of tryptophan to serotonin in the brain and spinal cord.

Question 44

Therapy of phenylketonuria (PKU)

Answer 44

- Diet therapy - Early detection is a must

Question 45

- Absence of homogentisic acid oxidase activity. - Inherited as a single gene recessive trait

Answer 45

Alkaptonuria

Question 46

Alkaptonuria: - Absence of __ __ __ activity. - Inherited as a __ __ __ trait

Answer 46

- homogentisic acid oxidase - single gene recessive

Question 47

Effect of alkaptonuria

Answer 47

pigmentation called ochronosis of the ear and eyes.

Question 48

Individuals afflicted with alkaptonuria secrete __ __ (also called __ or __ __ __) in urine - this compound turns black when urine stands.

Answer 48

- homogentisic acid - alkapton - 2,5 dihydrophenylacetic acid

Question 49

Alkaptonuaria: Homogentisic acid also accumulates in __ __, leading to a darkening of the nose, eyes and ears.

Answer 49

cartilaginous tissues

Question 50

the condition of alkaptonuria is associated with a type of __.

Answer 50

arthritis

Question 51

* A hereditary disorder involving the absence or reduction of melanin; an autosomal recessive trait. * Absence of enzyme tyrosinase needed in the production of melanin.

Answer 51

albinism

Question 52

Albinism * A hereditary disorder involving the absence or reduction of __; an __ __ trait. * Absence of enzyme __ needed in the production of __.

Answer 52

- melanin - autosomal recessive - tyrosinase - melanin

Question 53

- Albinos are susceptible to __, __ __ and __. - Allele for Albinism is favored by natural selection (sexual selection) in the two __ tribes (cultural practices)

Answer 53

- sunburn - skin cancer - blindness - Indian