The synthesis of lispro insulin

A person with Type 1 diabetes ran out of her prescription insulin and has not been able to inject insulin for the past 3 days. An overproduction of which of the following could cause a metabolic acidosis ?

  1. Hemoglobin
  2. Ketone bodies
  3. HCl
  4. Bicarbonate
    (Ketone bodies are weak acids. In diabetic ketoacidosis, the liver produces ketone bodies, which will reduce the brain’s dependency on glucose as its sole energy source. This is due to the lack ofinsulin, and the liver switching to starvation mode owing to the constant signaling by glucagon. Hemoglobin in the red blood cells and bicarbonate, both in the red blood cells and the plasma, are two of the body’s major buffers, and their overproduction would not lead to an acidosis. HCl overproduction within the stomach might lead to duodenal ulcers or gastroesophageal reflux, but not to an overall metabolic acidosis, as the protons do not find their way into the circulation. A loss of chloride, if severe enough, could produce a metabolic alkalosis, but not an acidosis. )

For the synthesis of lispro insulin (as described in the previous question), which one of the following changes in the coding for the B-chain would be required?

  1. CAAAAA to AAAAAC
  2. CCTAAT to AAACTC
  3. CCGAAG to AAACCA
  4. AAACCA to CCGAAG
  5. AAGCCT to AAACCC
    (The codons for proline are CCU, CCA, CCG, and CCC. The codons for lysine are AAA and AAG. The normal sequence of these two amino acids in the B-chain of insulin is pro-lys, so examples of this are CCGAAG, or CCCAAA. However, in the genetically engineered lispro variant of insulin, the lysine codon comes first, followed by the options of valine codons. The only answer that does this correctly is answer C. Answer A converts a pro-lys to a lys-asn. Answer B converts a pro-asn to lys-pro. Answer D converts a lys-pro to a pro-lys, and answer E converts a lys-pro to lys-pro. )

A 67-year-old woman weighing 50 kg undergoes mastectomy for breast cancer. Intraoperative blood loss is 525 mL.
What percentage is this blood loss of her estimated blood volume?

  1. 5%
  2. 10%
  3. 15%
  4. 20%
  5. 25%
    (In this patient, estimated blood volume should be calculated using 70mL/kg, i.e. 3500mL so 525mL is 15% of the patient’s estimated blood volume. In obese patients, this would lead to an overestimate of blood volume so a value of 45–55mL/ kg of actual body weight should be used. Young children have a higher blood volume by weight approximately 80–90mL/kg.

It is important to consider blood loss in the context of estimated blood volume so its full significance can be understood. A similar blood loss (525mL) in an 8-year-old, 25 kg child would probably put the child into class III hypovolaemic shock. This should be taken in the clinical context as intraoperative blood loss is difficult to estimate so heart rate, blood pressure, capillary refill time, peripheral perfusion, urine output, etc. should be considered in conjunction with any estimated blood loss. Postoperatively a drain can be useful in gauging ongoing blood loss but remember that drains can become blocked or be dislodged so they may not fill even in the context of significant bleeding.)

A patient with a hyperlipoproteinemia would most likely benefit from a lowcarbohydrate diet if the lipoproteins that are elevated in the blood belong to which class of lipoproteins? Choose the one best answer.

  1. Chylomicrons
  2. VLDL
  3. LDL
  4. HDL
  5. Chylomicrons and VLDL
    (VLDL is produced mainly from dietary carbohydrate, LDL is produced from VLDL, and chylomicrons contain primarily dietary triacylglycerol. Elevated HDL levels are desirable and are not considered to be a lipid disorder. HDL also contains low levels of triglyceride. A low-carbohydrate diet would be expected to reduce the level of circulating VLDL due to reduced fatty acid and triglyceride synthesis in the liver.)

A 52-year-old man, after suffering a heart attack, was put on 81 mg of aspirin daily by his cardiologist. The purpose of this treatment is to reduce the levels of which one of the following?

  1. Cytokines
  2. Leukotrienes
  3. Thromboxanes
  4. Cholesterol
  5. Triglycerides

(Ethanol is both water- and lipid-soluble. It is easily absorbed from the gastrointestinal tract and is distributed throughout the body via the blood stream. It is mostly metabolized in the livelj so the level would be high in this tissue. It is lipid-soluble, so it would be found in fatty tissue. It has many central effects in the brain, so it easily passes the bloodbrain barrier. The central cornea has no arterial supply. The only way alcohol could accumulate in the central cornea would be through diffusion into the aqueous humor and then into the central cornea, a slower and less-efficient system. Therefore, the tissue with the lowest level of alcohol would be the central cornea.)