2024 VJC H2 Bio P3 MS

1 2024 H2 Biology Prelim Paper 3 Answer 1 Thyroid hormones are produced and released by the thyroid gland. In humans, the thyroid gland is found in the neck below the Adam’s apple. It is lined with thyroid follicular cells, also called thyrocytes, that surround a lumen. Fig. 1.1 shows the thyroid follicular cells. Fig. 1.1 Unlike most hormones with specific target cells or tissues, the thyroid hormones act on nearly every cell in the body and are important in regulating the basal metabolic rate of the body. They regulate the metabolism of proteins, fat and carbohydrates in cells, affecting protein synthesis and cellular respiration. They are also involved in the control of heat generation in the body and are essential for proper cell development and differentiation. There are two types of thyroid hormones, namely triiodothyronine (T3) and thyroxine (T4). Their structures differ by the number of iodine present. Fig. 1.2 shows the structure of T3 and T4. Fig. 1.2 (a) With reference to Fig. 1.1 and 1.2, (i) suggest how thyroid hormones are able to act on nearly every cell in the body. [1]

2 • Thyroid hormones are secreted into the capillaries and carried throughout the body by the circulatory system / via the blood; (ii) compare the structure of thyroid hormones to an amino acid. [2] Similarity • Both thyroid hormones and amino acid have a central carbon bonded to a hydrogen atom, an amino group, a carboxyl group and a variable R group; (accept mention of just 1 of the groups) Difference • Thyroid hormones contain iodine atoms but not amino acids; (b) The release of thyroid hormones from the thyroid gland is regulated by other hormones released from the brain. Neurones in the hypothalamus in the brain release thyrotropin - releasing hormone (TRH), which stimulates the release of thyroid -stimulating hormone (TSH) from cells in the anterior pituitary. TSH then stimulates the release of T3 and T4 from the thyroid gland. Fig. 1.3 shows the relationship between different tissues in the control of the release of thyroid hormones. Fig. 1.3 Research was conducted to study the effect of TSH on the release of thyroid hormones from the thyroid gland. In this research, pluripotent stem cells were induced to differentiate into a culture of thyroid follicular cells. TSH was then introduced into the culture medium

3 of this cell culture, and the amount of T 3 and T 4 released into the culture medium was measured for a period of one week. The result of this experiment is shown in Fig. 1.4. Fig. 1.4 With reference to Fig. 1.4, (i) compare the changes in the levels of T3 and T4 in the cell culture medium during the week. [2] Similarity • The levels of both T3 and T4 decreased in general; Difference • The starting level of T3 was lower at 8.8 µg/mL than that of T3 at 2.8 mg/mL; • The level of T 3 decreases at a faster rate , from 8.8 µg/mL in day 1 to 1.8 µg/mL in day 7, compared to that of T4 from 2.8 mg/mL in day 1 to 1.2 µg/mL in day 7; (ii) contrast the release of thyroid hormones with the release of antibodies. [1] • Thyroid hormones were released on the same day that TSH was introduced, while antibodies are released a few days after an antigen is introduced; (c) The research continued and managed to discover the signalling pathways involved in the stimulation of the thyroid gland by TSH. The action of TSH on the thyroid follicular cells in the thyroid gland is shown in Fig. 1.5.

4 Fig. 1.5 (i) Identify the proteins labelled A and B. [2] • A: adenyl cyclase; • B: G protein; (ii) Explain the significance of protein A in TSH signalling. [3] • Upon activation by the binding of the G protein, adenyl cyclase catalyses the conversion of ATP to cAMP, resulting in an increase of cAMP concentration in the cytoplasm; • (4 molecules of) cAMP bind to protein R (dimer), resulting in the release of active PKA (dimer) from protein R (dimer); • Active PKA catalyses the phosphorylation of other kinases / relay proteins, triggering the phosphorylation cascade / signal transduction pathways that result in cellular responses in the thyroid follicular cells for the synthesis and secretion of thyroid hormones; (iii) Ca2+ ions are released from an organelle in the thyroid follicular cell when the cell is stimulated by TSH. Describe how the structure of this organelle allows its roles in TSH signalling. [3] • Ref. to the organelle as the smooth endoplasmic reticulum (sER); • Lumen surrounded by membrane impermeable to Ca2+ allows storage of high concentration of Ca2+ ions (higher concentration than cytoplasm) in the lumen of the sER; • Presence of IP3-gated Ca2+ channels on the membrane of sER, which open when bound by IP3, allows the facilitated diffusion of Ca2+ from the lumen of sER into the cytoplasm;

5 • Ca2+ bind to and activate Ca2+-dependent protein kinase to catalyse the phosphorylation of other kinases / relay proteins, triggering the phosphorylation cascade / signal transduction pathways that result in cellular responses in the thyroid follicular cells for the synthesis and secretion of thyroid hormones; (d) Beside the action of TRH and TSH, another regulatory mechanism of thyroid hormones is via the supply of iodine, an important component of thyroid hormones. Most dietary iodine is reduced to iodide ions before absorption by the small intestine. The iodide ions are transported to the thyroid gland via the circulatory system and accumulated in thyroid follicular cells. Fig. 1.6 shows the uptake of iodide ions by a thyroid follicular cell. Fig. 1.6 With reference to Fig. 1.6 and your knowledge on transport across membrane, (i) calculate the number of ATP required in the uptake of 10 mol of iodide ions into the thyroid follicular cell. Leave your answer to 3 significant figures. Show your working in the space provided. [1] • 20 / 3 = 6.67 mol of ATP (3 s.f.); (ii) explain the need for transport proteins in the uptake of iodide ions into the thyroid follicular cell. [4] Need for hydrophilic environment • Iodide ions are charged and polar / hydrophilic, and cannot cross the cell surface membrane due to the hydrophobic core of the cell surface membrane;

6 • The iodide ion transport protein provides a hydrophilic channel / binding site to shield the iodide ions from the hydrophobic core to bring them into the cell; Need for Na+ gradient • Concentration of the iodide ions is higher in the cytoplasm inside the cell than in the capillary / The iodide ions is transported into the cell against its concentration gradient; • The iodide ions are transported into the cell together with Na+, which enters the cell down its concentration gradient; • The Na+-K+ pump transports Na+ out of the cell into the capillary against its concentration gradient, with energy from ATP hydrolysis, to set up a high Na+ concentration in the capillary; (iii) state two differences between the transport of iodide ions and thyroglobulin into the lumen of the thyroid gland. [2] feature of comparison transport of iodide ions into thyroid gland lumen transport of thyroglobulin into thyroid gland lumen mode of transport active transport exocytosis involvement of transport protein transport protein involved transport protein not involved involvement of vesicles iodide ions not packaged into vesicles thyroglobulin packaged into secretory vesicles (e) Thyroid hormones, unlike most protein hormones, are transported into target cells and bind to intracellular receptors known as thyroid hormone receptors (TRs). TRs often form heterodimers with retinoic X receptor (RXR) and act as a transcription factor for a wide variety of genes. The dimer binds to a thyroid hormone response element (TRE) on the DNA and recruits co-repressors to repress gene expression. Fig. 1.