BIOC 3003 TEST STUDY SET 2025/2026
Why do enzymatic disorders show recessive inheritance? - ANSWER Because most
mutations inactivate enzyme function rather than producing a novel activity (loss of
function mutation).
Give an example of a recessive enzymatic disorder. - ANSWER Phenylketonuria (PKU)
What are the symptoms of phenylketonuria? - ANSWER Symptoms include marked
irritability, severe vomiting, eczema, seizures and a must mouse like odour.
What is the cause of phenylketonuria? - ANSWER A mutation in phenylalanine
hydroxylase (PAH) prevents phenylalanine from being catalysed to tyrosine.
What kind of mutations are in PAH? - ANSWER Mutations include gross deletions,
missense mutations, premature stop codons and splicing mutations.
How do missense mutations operate in PAH? - ANSWER Missense mutations impair
enzyme activity by causing increased protein instability and aggregation.
What does the high incidence of PKU in some populations suggest? - ANSWER Suggests
that heterozygotes (carriers) may have an adaptive advantage.
What is the working hypothesis in this regards? - ANSWER Ochratoxin A is a mycotoxin
produced by species of mould and fungi that can infest stored grains. Food
contaminated with ochratoxin A can result in human foetal death. A pregnant woman
eating such food may miscarry, but if she is heterozygous for PKU the higher
concentration of phenylalanine in her blood could protect the foetus.
Give an example of a dominant enzymatic disorder. - ANSWER Hereditary Sensory
Neuropathy Type 1 (HSN1).
What are the characteristics of HSN1? - ANSWER Characterized by progressive
degeneration of dorsal root ganglia. Late onset of symptoms (2nd or 3rd decade). Loss
of sensation (pain and touch) can lead to skin ulceration and loss of digits. Only
palliative treatment is available. It is the most common hereditary disorder of peripheral
sensory neurons.
What is thought to cause HSN1? - ANSWER Thought to be due to an increase in SPT
(serine palmitoyltransferase) activity. In neurons this results in increased de novo
ceramide synthesis and apoptosis of cells.
Describe SPT - ANSWER Serine palmitoyltransferase catalyzes the first step in the
biosynthesis of sphingolipids (including ceramide and sphingomyelin). Consists of two
subunits SPTLC1 and SPTLC2 encoded by separate genes. Both are needed for activity.
Why do structural proteins generally show dominant inheritance? - ANSWER Because
,these proteins are usually involved in macromolecular complexes. Mutant proteins are
able to modify the function of these complexes (gain of function mutations).
Give an example of a recessive structural protein disorder. - ANSWER Duchenne and
Becker muscular dystrophies.
Describe features of Duchenne and Becker muscular dystrophies. - ANSWER Affected
boys develop muscle weakness at age 3, (death occurs in early 20s). Incidence is
1/3300. Becker (non-lethal) is much milder phenotype. Both result from mutations in
Dystrophin.
What does Dystrophin do? - ANSWER Dystrophin links the actin filaments of muscle cells
to the extracellular matrix (laminins). When the protein is not there, the force exerted by
contraction cannot be converted to the muscle. Therefore there is no movement,
degeneration of muscle and eventually breathing problems.
Which kinds of mutations are more likely to produce BMD? - ANSWER Deletions (non
frameshifting) in the rod domain.
Which kinds of mutations are more likely to produce DMD? - ANSWER Deletions in the
Actin binding or C terminal domains or frameshifting deletions in the rod domain.
Why don't female carriers of Muscular Distrophy show any sign of muscle weakness? -
ANSWER Because of the random inactivation of the X chromosome.
Give an example of a dominant structural protein disorder. - ANSWER Collagen and
keratin disorders.
How many types of collagen are there? - ANSWER 23
Describe the collagens. - ANSWER Collagens are a family of fibrous proteins that are
major component of ECM. They consist of helical subunits (α chains) about 1000 amino
acids long, proline and glycine rich. The three α chains combine to give a triple helix.
What is the characteristic repeated motif of collagen? - ANSWER G-X-X
What is each type 1 collagen chain made of? - ANSWER 3 pro collagen peptides. Two
proα1 chains (encoded by COL1A1) and one proα2 chain (encoded by COL1A2).
What are some examples of fibril arrangements in collagen? - ANSWER Wicker like -
multidirectional forces
, Parallel bundles - linear forces
Alternate layers perpendicular (plywood array) - strength
Interwoven with elastin - elastic fibers
What are the steps in collagen synthesis? - ANSWER 1. Single poplypeptides of Collagen
subunits are translated by the ribosome and trafficked to ER
2. Hydroxylation of lysine and proline side chains allowing inter chain hydrogen
bonding)
3. The triple helix is formed
4. Procollagen is converted to tropocollagen by procollagen peptidase (N-/C- termini
cleaved)
5. Bundles form
6. Cross links form to stabilise (lysine)
--> Gives tensile strength.
What are the causes of collagen disorders? - ANSWER Can be caused by aberrations in
collagen synthesis or processing or by changes in collagen structure.
What happens when there is too much/little of collagen? - ANSWER Too much: fibrosis
and keloid formation.
Too little: wound healing and tissue fragility.
List some examples of diseases associated with improper collagen assembly. - ANSWER
Ehlers-Danlos syndrome
Osteogenesis Imperfecta
Scurvy
Dystrophic Epideromolysis Bullosa
Junctional Epidermolysis Bullosa
Why do enzymatic disorders show recessive inheritance? - ANSWER Because most
mutations inactivate enzyme function rather than producing a novel activity (loss of
function mutation).
Give an example of a recessive enzymatic disorder. - ANSWER Phenylketonuria (PKU)
What are the symptoms of phenylketonuria? - ANSWER Symptoms include marked
irritability, severe vomiting, eczema, seizures and a must mouse like odour.
What is the cause of phenylketonuria? - ANSWER A mutation in phenylalanine
hydroxylase (PAH) prevents phenylalanine from being catalysed to tyrosine.
What kind of mutations are in PAH? - ANSWER Mutations include gross deletions,
missense mutations, premature stop codons and splicing mutations.
How do missense mutations operate in PAH? - ANSWER Missense mutations impair
enzyme activity by causing increased protein instability and aggregation.
What does the high incidence of PKU in some populations suggest? - ANSWER Suggests
that heterozygotes (carriers) may have an adaptive advantage.
What is the working hypothesis in this regards? - ANSWER Ochratoxin A is a mycotoxin
produced by species of mould and fungi that can infest stored grains. Food
contaminated with ochratoxin A can result in human foetal death. A pregnant woman
eating such food may miscarry, but if she is heterozygous for PKU the higher
concentration of phenylalanine in her blood could protect the foetus.
Give an example of a dominant enzymatic disorder. - ANSWER Hereditary Sensory
Neuropathy Type 1 (HSN1).
What are the characteristics of HSN1? - ANSWER Characterized by progressive
degeneration of dorsal root ganglia. Late onset of symptoms (2nd or 3rd decade). Loss
of sensation (pain and touch) can lead to skin ulceration and loss of digits. Only
palliative treatment is available. It is the most common hereditary disorder of peripheral
sensory neurons.
What is thought to cause HSN1? - ANSWER Thought to be due to an increase in SPT
(serine palmitoyltransferase) activity. In neurons this results in increased de novo
ceramide synthesis and apoptosis of cells.
Describe SPT - ANSWER Serine palmitoyltransferase catalyzes the first step in the
biosynthesis of sphingolipids (including ceramide and sphingomyelin). Consists of two
subunits SPTLC1 and SPTLC2 encoded by separate genes. Both are needed for activity.
Why do structural proteins generally show dominant inheritance? - ANSWER Because
,these proteins are usually involved in macromolecular complexes. Mutant proteins are
able to modify the function of these complexes (gain of function mutations).
Give an example of a recessive structural protein disorder. - ANSWER Duchenne and
Becker muscular dystrophies.
Describe features of Duchenne and Becker muscular dystrophies. - ANSWER Affected
boys develop muscle weakness at age 3, (death occurs in early 20s). Incidence is
1/3300. Becker (non-lethal) is much milder phenotype. Both result from mutations in
Dystrophin.
What does Dystrophin do? - ANSWER Dystrophin links the actin filaments of muscle cells
to the extracellular matrix (laminins). When the protein is not there, the force exerted by
contraction cannot be converted to the muscle. Therefore there is no movement,
degeneration of muscle and eventually breathing problems.
Which kinds of mutations are more likely to produce BMD? - ANSWER Deletions (non
frameshifting) in the rod domain.
Which kinds of mutations are more likely to produce DMD? - ANSWER Deletions in the
Actin binding or C terminal domains or frameshifting deletions in the rod domain.
Why don't female carriers of Muscular Distrophy show any sign of muscle weakness? -
ANSWER Because of the random inactivation of the X chromosome.
Give an example of a dominant structural protein disorder. - ANSWER Collagen and
keratin disorders.
How many types of collagen are there? - ANSWER 23
Describe the collagens. - ANSWER Collagens are a family of fibrous proteins that are
major component of ECM. They consist of helical subunits (α chains) about 1000 amino
acids long, proline and glycine rich. The three α chains combine to give a triple helix.
What is the characteristic repeated motif of collagen? - ANSWER G-X-X
What is each type 1 collagen chain made of? - ANSWER 3 pro collagen peptides. Two
proα1 chains (encoded by COL1A1) and one proα2 chain (encoded by COL1A2).
What are some examples of fibril arrangements in collagen? - ANSWER Wicker like -
multidirectional forces
, Parallel bundles - linear forces
Alternate layers perpendicular (plywood array) - strength
Interwoven with elastin - elastic fibers
What are the steps in collagen synthesis? - ANSWER 1. Single poplypeptides of Collagen
subunits are translated by the ribosome and trafficked to ER
2. Hydroxylation of lysine and proline side chains allowing inter chain hydrogen
bonding)
3. The triple helix is formed
4. Procollagen is converted to tropocollagen by procollagen peptidase (N-/C- termini
cleaved)
5. Bundles form
6. Cross links form to stabilise (lysine)
--> Gives tensile strength.
What are the causes of collagen disorders? - ANSWER Can be caused by aberrations in
collagen synthesis or processing or by changes in collagen structure.
What happens when there is too much/little of collagen? - ANSWER Too much: fibrosis
and keloid formation.
Too little: wound healing and tissue fragility.
List some examples of diseases associated with improper collagen assembly. - ANSWER
Ehlers-Danlos syndrome
Osteogenesis Imperfecta
Scurvy
Dystrophic Epideromolysis Bullosa
Junctional Epidermolysis Bullosa
