AQA GCSE Biology Biology Paper 2 (Higher), June 2022: Question 5

14 marks · Standard Demand difficulty · Short Answer

Analyze the inheritance of maple syrup urine disease (MSUD) using a pedigree tree and Punnett square, and explain the biochemical and physiological consequences of the enzyme deficiency.

Practise this question

Question

The question presents a pedigree chart (Figure 4) showing three generations of a family with maple syrup urine disease (MSUD), an inherited recessive condition. Individuals 1 and 2 (unaffected) have children 5 (affected female) and 6 (unaffected male). Individual 7 (unaffected female) mates with individual 8 (unaffected male, son of unaffected male 3 and affected female 4, brother of unaffected male 9). Individuals 7 and 8 have three children: unaffected male 10, unaffected female 11, and affected male 12. Figure 5 shows a biochemical pathway where amino acids are acted upon by Enzyme 1 to produce toxic substance P and ammonia. Toxic substance P is converted by Enzyme 2 into harmless products, while ammonia is converted by other enzymes into urea. It notes that a person with MSUD cannot make Enzyme 2.
Question text

05 Maple syrup urine disease (MSUD) is a rare inherited human condition.

MSUD is usually diagnosed early in childhood and can be controlled by having a

low-protein diet.

Figure 4 shows the inheritance of MSUD in one family.

Figure 4

The allele for MSUD is recessive.

05.1 Give one piece of evidence from Figure 4 which shows that MSUD is a

recessive condition.

[1 mark]

05.2 Persons 7 and 8 in Figure 4 are expecting a fourth child.

Determine the probability that the child will have MSUD.

You should:

• draw a Punnett square diagram

• identify the phenotype of each offspring genotype

• use the symbols:

N = allele for not having MSUD

n = allele for MSUD.

[4 marks]

Probability =

Figure 5 shows chemical reactions involved in the normal breakdown of some types

of amino acid inside body cells.

Figure 5

A person with MSUD cannot make Enzyme 2.

05.3 One of the final products shown in Figure 5 is urea.

Where in the human body are the reactions shown in Figure 5 most likely to occur?

[1 mark]

Tick ( ) one box.

Kidney

Liver

Pancreas

Small intestine 19

Scientists can analyse blood samples or urine samples to see if a person has MSUD.

The test identifies high concentrations of toxic substance P, shown in Figure 5.

05.4 Explain why the blood of a person with MSUD will have a high concentration of

toxic substance P.

Use information from Figure 5.

[3 marks]

05.5 Explain why the urine of a person with MSUD will have a high concentration of

toxic substance P.

[2 marks]

05.6 Explain why a person with MSUD must have a low-protein diet.

[3 marks]

Mark scheme

Show the mark scheme Mark scheme for Question 5 outlining answers and guidance across six sub-questions. 05.1 awards 1 mark for identifying that unaffected parents have an affected child (e.g., 1 and 2 have 5, or 7 and 8 have 12). 05.2 awards 4 marks for correct gametes (N and n for each parent), Punnett square genotypes (NN, Nn, Nn, nn), correct phenotypes identified, and a probability of 0.25 (or 25%, 1/4, 1 in 4). 05.3 awards 1 mark for liver. 05.4 awards 3 marks for: no enzyme 2 so cannot break down toxic substance, toxic substance builds up from amino acids, and toxic substance diffuses into blood. 05.5 awards 2 marks for substance P passing through the kidney filter and not being reabsorbed. 05.6 awards 3 marks for proteins being made of amino acids, low-protein diet reducing amino acid levels, preventing build-up of toxic substance P and avoiding organ damage.

Question 5

AO /

Question Answers Extra information Mark

Spec. Ref.

05.1 parents without MSUD have a allow 1 and 2 (without MSUD) 1 AO3

child with MSUD have child 5 (with MSUD) 4.6.1.6

or 4.6.1.7

7 and 8 (without MSUD) have

child 12 (with MSUD)

ignore MSUD skips a generation

AO /

Spec. Ref.

05.2 gametes correct: 1 AO2

N + n and N + n

correct derivation of offspring allow correct for gametes stated 1 AO2

genotypes:

NN Nn Nn nn

correct phenotype for each allow correct for offspring 1 AO2

genotype genotypes

ignore carrier

AO3

correct probability: allow correct answer only 1

0.25 / ¼ / 25% / 1 in 4 allow 1:3

do not accept 1 in 3 / 1:4 4.6.1.6

4.6.1.7

AO /

Spec. Ref.

05.3 liver 1 AO2

4.5.3.3

AO /

Spec. Ref.

16 allow P for toxic substance

05.4 throughout AO2

4.2.2.1

(no enzyme 2 made so) cannot allow (no enzyme 2 made so) 1 4.1.3.1

break down the toxic substance cannot change toxic substance 4.6.1.5

into harmless products 4.6.1.6

the toxic substance is still made allow toxic substance builds up 1

(from the amino acids) over time

ignore concentration of toxic

substance is high(er)

toxic substance diffuses / moves 1

(from cells) into the blood ignore incorrect name of organ

AO /

Spec. Ref.

05.5 the toxic substance passes 1 AO1

through filter in kidney 4.5.3.3

or

P passes through filter in kidney

(some / all) not reabsorbed allow (some / all) not absorbed 1

back into the blood

or (some / all) not taken back

into the blood

ignore (some / all) not absorbed

into the blood

or (some / all) not taken into the

blood

AO /

Spec. Ref.

05.6 proteins contain amino acids allow proteins are broken down 1 AO1

or into amino acids

proteins are made of amino

acids

must keep (certain) amino acids allow (so) (certain) amino acids 1 AO2

in low amount do not build up

allow (so) less of (certain) amino

acids are produced AO2

(so) toxic substance or P does 1

not build up in the body and 4.6.1.5

cause damage to cells / tissues / 4.6.1.7

organs 4.4.2.3

Total Question 5 14

How to answer it

Inheritance of MSUD & Protein Metabolism

What this question tests

This 14-mark question assesses core understanding across genetics and human organ systems:

  • Pedigree Analysis: Deducing recessive inheritance from a family tree.
  • Genetic Crosses: Constructing a 4-mark Punnett square with phenotypes and calculating offspring probability.
  • Deamination & Urea Formation: Recalling that amino acid breakdown and urea production occur in the liver.
  • Biochemical Cascades & Excretion: Explaining accumulation of toxic metabolic intermediates, kidney filtration, and dietary management.
Question 05.1 (1 mark)

Evidence for Recessive Inheritance

Identifying proof that the MSUD allele is recessive from Figure 4

✅ Mark Scheme Answer

Any one of the following clear observations:

  • Parents without MSUD have a child with MSUD.
  • Parents 1 and 2 (unaffected) have child 5 (affected).
  • Parents 7 and 8 (unaffected) have child 12 (affected).

❌ Common Errors & Examiner Warning

  • "MSUD skips a generation": Gained 0 marks. This is an observation, not scientific evidence of recessiveness.
  • Vague statements like "because 4 has it and 8 doesn't" do not prove recessiveness.
Mark scheme guidance: 1 mark for AO3. Must state both that the parents do not have the condition and that their child does (or cite specific IDs like 7 & 8 having 12).
Question 05.2 (4 marks)

Punnett Square Genetic Cross

Determining the probability of child 4 having MSUD

💡 Step 1: Deducing Parental Genotypes

Parents 7 and 8 already have an affected child (12), whose genotype must be nn .

Therefore, both parents must carry the recessive allele while being unaffected themselves: both are heterozygous ( Nn ).

📐 Step 2: Punnett Square & Derivation

N n
N NN
Unaffected 		Nn
Unaffected
n Nn
Unaffected 		nn
Has MSUD

✅ Mark Breakdown (4 Marks)

  • Mark 1: Correct parental gametes identified: N + n and N + n .
  • Mark 2: Correct offspring genotypes derived: NN, Nn, Nn, nn .
  • Mark 3: Correct phenotypes matched to genotypes:
    • NN and Nn = Unaffected / Does not have MSUD
    • nn = Has MSUD.
  • Mark 4: Probability stated correctly: 0.25, ¼, 25%, or 1 in 4 (also allow 1:3 ratio).

❌ Common Errors

  • Writing ratio probability as 1 in 3 or 1:4 (1:4 as a ratio means 1 out of 5, which loses the final mark).
  • Forgetting to state which genotype produces which phenotype.
Question 05.3 (1 mark)

Site of Urea Formation

Where the reactions in Figure 5 occur in the human body

✅ Correct Answer

☑ Liver

🧠 Exam Technique & Recall

Deamination of excess amino acids into ammonia and subsequently into urea happens exclusively in the liver.

The kidneys filter and excrete urea, but they do not make it!

Question 05.4 (3 marks)

High Concentration of Substance P in Blood

Explaining why toxic substance P accumulates in the blood of MSUD patients

✅ Marking Points (3 marks)

  1. Enzyme defect: MSUD patients lack Enzyme 2, so substance P cannot be broken down into harmless products.
  2. Continued production: Substance P is still continuously formed from amino acids by Enzyme 1.
  3. Movement into blood: Substance P diffuses / moves from cells into the blood.

🧠 Flowchart Strategy

Always trace the path through the provided diagram:

Amino acids ➔ (Enzyme 1 works) ➔ Substance P builds up ➔ (Blocked by lack of Enzyme 2) ➔ Diffuses into blood .

Question 05.5 (2 marks)

High Concentration of Substance P in Urine

Connecting kidney filtration to the excretion of substance P

✅ Marking Points (2 marks)

  1. Filtration: Substance P is small enough to pass through the filter / basement membrane in the kidney (into the nephron filtrate).
  2. Lack of Reabsorption: Substance P is not reabsorbed (or not taken back) into the blood, so it passes out into the urine.

❌ Common Errors

  • Saying "it is not absorbed into the blood" without using the word back or reabsorbed loses Mark 2. The substance was already in the blood!
Question 05.6 (3 marks)

Why a Low-Protein Diet is Essential

Explaining the treatment rationale for MSUD

✅ Marking Points (3 marks)

  1. Protein digestion: Proteins are broken down into amino acids (or proteins are made of amino acids).
  2. Limiting substrate: A low-protein diet keeps the level of these specific amino acids low in the body.
  3. Preventing damage: This prevents toxic substance P from accumulating and causing harm/damage to cells, tissues, or organs (such as the brain).

🧠 Clear Cause-and-Effect Chain

To secure full marks on 3-mark explanation questions:

Dietary intake (less protein) ➔ Digestive breakdown (fewer amino acids) ➔ Biochemical outcome (less toxic P made, preventing organ damage).

Topics

Biology · B1: Cell Biology · B2: Organisation · B5: Homeostasis and Response · B6: Inheritance, Variation and Evolution

Question and mark scheme from the AQA GCSE Biology examination, Biology Paper 2 (Higher), June 2022. QuestionVault is an independent revision resource; questions remain the copyright of the awarding body.