Genetic aspects of metabolic disease

Question 1

What are in born errors of metabolism

Answer 1

They’re a class of genetic disease that alter metabolic pathways.

Question 2

Genetic mutations, what are they?

Answer 2

Changes in the nucleotide sequence of the DNA. E.g Substitution, Insertion, deletion

Question 3

2 Types of cause of mutation

Answer 3

Spontaneous (e.g replication errors, tautomerisation, deamination, depurination).

Induced (a bunch of them)

Question 4

Spontaneou

Answer 4

Replication errors - introduce wrong base at certain position, does this naturally. It will probably get repaired tho! Sometimes it won’t tho bc it can’t be recognised.

Tautomeric shifts - Bases of DNA subject to spontaneous changes.

Sometimes Amino group (single bond) of A or C change to imino group (double bond)

Sometimes Keto group (C=O) of G or T change to Enol group (C-OH) loss of double bond.

Deamination - cut off amino group, change to =o. C becomes Uracil, A becomes Hypoxanthine (pairs C), G becomes Xanthine (pairs C). These can be repaired.
Methylation of C makes T, which cannot be repairs

Depurination - base it cut off at the sugar bond. Cell has to guess which nucleotide it has to place in replication. (

Question 5

What does Ethidium bromide do to a sequence

Answer 5

Inserts itself so new sequence will have to guess what to put in its place. So results in completely different daughter cell sequence

Can also cause deletion

Question 6

Types of metabolic disorders

Answer 6

Anabolic - stopping the build up into larger units. This could lead to a deficiency in the larger metabolites we might need

Catabolic - stopping breakdown into smaller metabolites.

Storage - Stopping the breakdown of storage molecules to smaller monomers.

Question 7

Examples of inborn errors of metabolism

Answer 7

Phenylketonuria (PKU) - affects Amino acids metabolism

Glycogen storage diseases - CHO

Familial hypercholesterolaemia - Cholesterol

Question 8

PKU

Answer 8

Autosomal reccesive disorder, mutation in PAH gene (phenylalanine).

Prevents it from metabolising. Build up of phenylalanine within blood and urine.

If it’s >20mg/dL, normally <2mg/dL

NORMALLY:

PAH breaks down Phe to Tyr, this occurs via BioH4>BioH2 via Dihydropteridine reductase (helps recycle the BioH4). In ON

Question 9

What is PKU type 4?

Answer 9

Fully functioning PAH enzyme but mutant Dihydropteridine reductase which recycles the cofactor BioH4. This means PAH enzyme can’t work anymore.

Question 10

4 enzymes involved in glycogen breakdown and what do they do.

Answer 10

1. Glycogen phosphorylase (only works on 1>4 linage):

converts glycogen to Glucose 1-phosphate.

2. Glycogen debranching enzyme (works on 1,6 linkage)
3. Phosphoglucomutase

Glucose-1-phosphate > G-6-P

4. G-6-phosphatase

Converts G-6-P to glucose

Question 11

Von gierke disease - glycogen storage disease 1

Answer 11

Deficiency in G-6-phosphotase so can’t convert G-6-P to glucose. This increases Glycolysis to then increase lactate.

Results in hypoglycaemia so people w this have to keep eating

Question 12

McArdles disease - glycogen storage disease

Answer 12

Glycogen phosphorylase is absent so Glycogen can’t be converted to Glucose-1-phosphate

Leads to muscle weakness, not enough energy for exercise.

Question 13

Familial hypercholesterolaemia (Glycogen storage disease)

Answer 13

Liver normally regulates cholesterol.

LDL-R receptor has mutation so won’t recognise apolipoprotein with cholesterol so it will be built up in the blood.

Mutation in apolipoprotein, results in not able to recognize LDL-R.

Mutation in heterozygous gene: 50% reduction in LDL-R, liver can’t take up as much cholesterol as they can.

Mutation in homozygous:
no LDL-R at all, death before age 20!