UKPSC Prelims 2024 General Studies Paper-I · Question 83 of 147

Correct — C, Insulin.

Insulin is a small protein of 51 amino acids, so its gene can be cut out, pasted into a plasmid and expressed in a bacterium.

Genentech did this in E. coli in 1978, and Eli Lilly's Humulin, approved in the United States in October 1982, became the first recombinant human hormone sold as a medicine.

The idea to carry away: recombinant DNA technology makes gene products, that is proteins and peptides. Of the four options, insulin is the one hormone that is a protein.

The other three are steroids or an iodinated amino acid, which cells build with enzymes rather than read off a gene.

Until then diabetics used insulin extracted from the pancreas of slaughtered cattle and pigs.

It differs from human insulin by three and one amino acids respectively, and some patients developed allergic reactions to the foreign protein. That supply and purity problem is what recombinant insulin solved.

• (a)
  Estrogen — Estrogen (estradiol) is a steroid, assembled from cholesterol by a chain of enzymes rather than encoded by a gene, so a cloned gene in a bacterium cannot yield it directly. Pharmaceutical estrogens are made by chemical synthesis.

  It is the right answer when a paper asks for the ovarian hormone secreted by the growing Graafian follicle, the hormone behind female secondary sexual characters and the proliferative phase of the menstrual cycle.

• (b)
  Testosterone — Testosterone is likewise a steroid derived from cholesterol. Expressing a cloned gene gives a protein, not a steroid, so recombinant DNA technology is the wrong tool for it; medicinal testosterone is produced by chemical synthesis.

  It is the right answer for the androgen secreted by the Leydig (interstitial) cells of the testis under luteinising hormone, and for the hormone behind male secondary sexual characters and spermatogenesis.

• (d)
  Thyroxine — Thyroxine (T4) is an iodinated derivative of the amino acid tyrosine, not a protein.

  The thyroid makes it by attaching iodine to tyrosine residues held on the protein thyroglobulin, so it is a modified amino acid rather than the product of a gene that could be cloned. The tablet form, levothyroxine, is chemically synthesised.

  It is the right answer for the iodine-containing hormone whose deficiency causes goitre, cretinism in children and myxoedema in adults, and for the hormone that sets basal metabolic rate.

Recombinant DNA technology joins a DNA fragment from one organism to a vector, commonly a plasmid, and puts the construct into a host cell, which then expresses the gene.

Whatever the host makes is a gene product, which limits the direct output to proteins and peptides.

Hormones fall into chemical classes: peptide or protein hormones (insulin, glucagon, growth hormone), steroids (estrogen, testosterone, cortisol), iodothyronines (thyroxine) and amino-acid derivatives (adrenaline).

Of these, the peptide class is the direct gene product, which is why insulin was the natural first target.

• Human insulin has 51 amino acids in two chains, A (21) and B (30), joined by disulphide bridges.
• In the body insulin is made as proinsulin; the connecting C-peptide is cut out during maturation to give the active hormone.
• Genentech expressed synthetic genes for the A and B chains separately in E. coli in 1978, then joined the chains chemically.
• Humulin, marketed by Eli Lilly, received United States approval in October 1982 as the first recombinant human hormone medicine.
• NCERT Class XII dates Eli Lilly's insulin work to 1983 and describes the same A-chain and B-chain method.
• Animal insulin from cattle differs from human insulin by three amino acids; pig insulin differs by one.
• Frederick Sanger worked out the amino-acid sequence of insulin, the first protein to be sequenced, and received the 1958 Nobel Prize in Chemistry for it.
• Recombinant human growth hormone (1985) replaced hormone extracted from cadaver pituitaries, which had transmitted Creutzfeldt-Jakob disease.
• Insulin and glucagon are peptides; estrogen, testosterone and cortisol are steroids; thyroxine is an iodinated tyrosine derivative.
• Biocon launched Insugen, an Indian recombinant human insulin made in Pichia pastoris, in 2004.

• The word hormone pulls attention to glands; the deciding property is chemistry. Three options are steroids or an iodinated amino acid, and a bacterium given a cloned gene makes protein, not steroid.
• Somatostatin, a 14-amino-acid hormone, was expressed in E. coli in 1977 as a laboratory demonstration; insulin was the first to reach patients. Read whether a stem asks for the first laboratory expression or the first medicine. Here somatostatin is absent and insulin is the one protein offered.
• NCERT gives 1983 for Eli Lilly's insulin work while the United States approval of Humulin came in October 1982; a date option a year off is not a different product.
• Growth hormone is also a recombinant protein hormone but came later, in 1985; if it appears beside insulin, insulin is the earlier one.
• Insulin analogues such as lispro and glargine are later engineered variants of the molecule, not the first recombinant product.

• practice — not a real PYQ

  Humulin, the first recombinant human insulin to be marketed, was produced by expressing the insulin-chain genes in which host organism?

  • (a)Saccharomyces cerevisiae
  • (b)Escherichia coli
  • (c)Agrobacterium tumefaciens
  • (d)Bacillus thuringiensis
  Answerb — Eli Lilly's Humulin used Genentech's E. coli process, in which the A and B chains were expressed separately and then joined.

  Saccharomyces cerevisiae is the yeast host Novo Nordisk later used for its own insulin, not Humulin.

  Agrobacterium tumefaciens is the natural genetic engineer of plants, used to carry genes into crops. Bacillus thuringiensis is the source of the cry genes behind Bt cotton.

• practice — not a real PYQ

  Before a recombinant version became available in 1985, which of the following human hormones used in medicine was extracted from the pituitary glands of cadavers?

  • (a)Insulin
  • (b)Growth hormone
  • (c)Adrenaline
  • (d)Thyroxine
  Answerb — Growth hormone is a pituitary protein, so before recombinant somatropin it was pooled from human cadaver pituitaries, a supply withdrawn after Creutzfeldt-Jakob disease cases.

  Insulin came from cattle and pig pancreas, not human tissue.

  Adrenaline was isolated from animal adrenal glands and has been chemically synthesised since the early 1900s. Thyroxine came from animal thyroid extract and is now synthesised chemically.

• practice — not a real PYQ

  Which one of the following hormones is chemically a steroid?

  • (a)Insulin
  • (b)Glucagon
  • (c)Cortisol
  • (d)Oxytocin
  Answerc — Cortisol is secreted by the adrenal cortex and is built from cholesterol, the defining origin of a steroid.

  Insulin and glucagon are peptide hormones of the pancreatic islets. Oxytocin is a nine-amino-acid peptide made in the hypothalamus and released from the posterior pituitary.

• practice — not a real PYQ

  Insulin is secreted by which of the following cells?

  • (a)Alpha cells of the islets of Langerhans
  • (b)Beta cells of the islets of Langerhans
  • (c)Delta cells of the islets of Langerhans
  • (d)Acinar cells of the pancreas
  Answerb — The beta cells of the islets of Langerhans secrete insulin, which lowers blood glucose. Alpha cells secrete glucagon, which raises it. Delta cells secrete somatostatin.

  Acinar cells are the exocrine part of the pancreas and release digestive enzymes into the pancreatic duct, not hormones into the blood.