2026 CJC H2 Biology 9477 P3 ANS

CATHOLIC JUNIOR COLLEGE JC2 PRELIMINARY EXAMINATIONS Higher 2 CANDIDATE NAME CLASS 2T INDEX NUMBER BIOLOGY 9477/03 Paper 3 Long Structured and Free Response Questions 15 September 2026 2 hours Candidates answer on the Question Paper. Additional Materials: Writing Paper READ THESE INSTRUCTIONS FIRST Write your name, class and index number in the spaces at the top of this page. Write in dark blue or black pen. You may use an HB pencil for any diagrams or graphs. Do not use staples, paper clips, glue or correction fluid. Section A Answer all questions in the spaces provided on the Question paper. Section B Answer any one question in this section on writing papers provided. The use of an approved scientific calculator is expected, where appropriate. You may lose marks if you do not show your working or if you do not use appropriate units. At the end of the examination, fasten your answers for Section B securely. The number of marks is given in brackets [ ] at the end of each question or part question. For Examiner’s Use 1 [32] 2 [12] 3 [11] 4 or 5 [20] TOTAL 75

2 This document consists of 25 printed pages and 1 blank page. [Turn over

3 Section A Answer all questions in this section. 1 The INSR gene encodes the insulin receptor , a transmembrane receptor protein found on the surface of many mammalian cells. The receptor binds to insulin and activates intracellular signalling pathways involved in regulating cellular metabolism. After transcription, the INSR pre-mRNA undergoes post-transcriptional processing. The pre-mRNA can be processed into many different mRNA molecules, which are translated to produce different isoforms of the insulin receptor. Figure 1.1 shows two pathways of post-transcriptional processing of INSR pre-mRNA in mammalian cells. Fig. 1.1 (a) (i) Outline the events involved in the expression of the INSR gene during post-transcriptional processing of the pre-mRNA. ………………………………………………………………………………….……………………… [3] 1. A 7- methylguanosine cap is added to the 5’ end of the pre-mRNA, (Accept 5’ guanosine cap / 5’ capping) 2. and a poly-A tail is added to the 3’ end of the pre-mRNA to stabilise the transcript and facilitate nuclear export.

4 3. Spliceosomes recognize intron-exon junction sequences to excise/ remove non-coding introns and spliced together coding exons together to form mature mRNA. (ii) In normal hepatocytes, insulin activates target cells that promote increased glycogen synthesis. Outline how insulin results in the initiation of cell signalling in a hepatocyte. ………………………………………………………………………………….……………………… [2] 1. Insulin binds complementarily to the binding site of the transmembrane receptor tyrosine kinase (TKR). 2. This induces a conformational change that promotes receptor dimerisation , leading to autophosphorylation of tyrosine kinase domains , thus activating downstream signal transduction cascades. OR This induces a conformational change that brings the two intracellular tyrosine kinase domains into close proximity , enabling cross-autophosphorylation of the intracellular β -subunits and activating downstream signal transduction cascades (iii) With reference to Fig. 1.1, describe how the mechanisms of post-transcriptional processing result in different receptor isoforms IR-A and IR-B, and suggest how the structural difference between the two isoforms results in different cellular responses. ………………………………………………………………………………….……………………… [4] 1. The mechanism is alternative RNA splicing , where spliceosome select alternative splice sites during pre-mRNA processing. 2. Exon 11 is retained/included in Pathway 1 but skipped/excised in Pathway 2, producing two distinct mature mRNA transcripts from the same pre-mRNA . 3. Exclusion of Exon 11 in IR-A removes a specific sequence of amino acids from the extracellular domain, changing the 3D tertiary conformation of the ligand-binding site 4. The difference in the structure changes the intracellular domain such that a different relay protein(s) binds to the activated receptor / OWTTE

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6 Gene mutations that occur within the INSR gene can directly change the receptor structure and function. Analysis of tissue samples from patients with liver carcinoma identified three distinct somatic variants mapping to functional domains of the receptor. Table 1.1 shows three different somatic mutations identified in liver cells. Table 1.1 Variant Location on INSR Gene DNA change Outcome 1 exon 2 (extracellular domain) nonsense mutation introducing a stop codon within the exon not responsive to insulin 2 exon 17 (intracellular domain) missense mutation locking the kinase domain in an active conformation cellular effects are present without insulin 3 exon 13 (transmembrane domain) missense mutation causing misfolding of a single α- helix less sensitive to insulin (iv) With reference to Table 1.1, suggest how the molecular mechanism of each mutation in variants 1 , 2 and 3 changes the structure and function of the insulin receptor, resulting in their observed outcomes. ………………………………………………………………………………….……………………… [6] Variant 1 [2 Marks] 1. (Mechanism/Structure): Any Point mutation (single a.a. substitution/deletion/addition) introduces a premature stop codon early in mRNA translation, resulting in a severely truncated / shortened polypeptide chain lacking the extracellular binding domain. 2. (Function/Effect): The truncated protein results in a total loss of functional / non-functional insulin receptors at the cell surface membrane. OR Insulin receptor loses its functional insulin-binding site , rendering the cell completely unresponsive to insulin / unable to bind insulin. OWTTE Variant 2 [2 Marks]

7 3. (Mechanism/Structure): Any Point mutation (single a.a. substitution/deletion/addition) in Exon 17 that permanently locks the intracellular tyrosine kinase domain in an active tertiary conformation. 4. (Function/Effect): Leads to constitutive / hyperactive