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Jack and his mother go to see their GPJack and his mother go to see their GP….. The doctor told Jack’s mother that The doctor told Jack s mother that Jack must not eat overnight before coming for the appointment with him
His fasting venous plasma glucose His fasting venous plasma glucose level gave a value of 8 mmol/l –normal is about 5 mmol/l
Let’s consider what we know about glucose, insulin and relevantglucose, insulin and relevant concepts before we think about a diagnosis and treatment for Jack....
Glucose transport across intestinal and renal epithelial cells occurs via a Na+‐glucose co‐transporter. Glucose transport across other cell membranes uses different transporters that are independent of Na+. Which of the following statements is CORRECT regarding glucoseWhich of the following statements is CORRECT regarding glucose transport across cell membranes?
A Glucose is water soluble and hence readily diffuses acrossA. Glucose is water soluble, and hence readily diffuses across cell membranes
B. Glucose is accumulated against its concentration gradient g gby glucose transporters in all cell types
C. Energy from ATP is required for the transport of glucose to i ll i h N + i d d loccur in cells with Na+‐independent glucose transporters
D. Na+/K+‐ATPase can indirectly drive active glucose transport across renal epithelial cell membranes
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across renal epithelial cell membranes
E. Na+ ions and glucose only move along their concentration gradients during co‐transport in intestinal cell membranes
A. B. C. D. E.
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Cotransport: active transport driven by a concentration gradient
There are several possibilities related to the structure of Jack’s insulin that could account for his present illness. In the back of his mind, Jack’s doctor recalls some basic knowledge of insulin from his studies at UQ Which concept is WRONG?his studies at UQ. Which concept is WRONG?
A. Insulin is expressed by the ribosome as i l l tid h ia single polypeptide chain
B. Insulin becomes active only upon l i lproteolytic cleavage
C. The active form of insulin is stabilized b i h i di lfid b dby an intrachain disulfide bond
D. The active form of insulin is stabilized
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by interchain disulfide bonds
E. Proinsulin is the fully folded and most
A. B. C. D. E.0 of 500
1010active form of insulin
His doctor considers the possibility that Jack has inherited the disease. He searches the web and finds that a leucine to valine mutation in insulin can lead to onset of diabetes.
Valine Leucine Aspartatep
V
pKa of carboxylate proton is 4Side‐chains are highlighted in pink
His doctor considers the possibility that Jack has inherited the disease. He searches the web and finds that a leucine to valine mutation in insulin can lead to onset of diabetes. Which of h ld NOT b i h d ’ ?these would NOT be correct in the doctor’s assessment?
A. Such a change would be described as a conservative substitution in gthe polypeptide sequence
B. A change at the DNA level must have resulted in the change from leucine to valine
C. The side chains of leucine and valine have the ability to form covalent bonds between each other thereby inactivating insulinbonds between each other, thereby inactivating insulin
D. Leucine is likely to be buried in the interior of insulin, a globular protein. Hence, this change may only mildly affect insulin function
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p g y y y
E. A change from leucine to aspartate at this site would be more likely to result in insulin not maintaining its folded 3‐dimensional structure
Introduction to next 2 questionsIntroduction to next 2 questions....
In a normal subject.....j
After eating a meal, increases in blood glucose stimulate l f i li f b t ll i threlease of insulin from beta cells in the pancreas.
Insulin acts on tyrosine kinase linked receptors to l f th bl dremove glucose from the blood.
Jack’s beta cells are not secreting insulin.
When blood glucose levels decrease below a set point, glucagon is secreted by alpha cells in the pancreas. Glucagon acts on G‐protein coupled receptors to
After a few weeks, including a short stay in hospital, Jack is stabilized on daily insulin injections with topup doses at meal times. Which statement is INCORRECT?
A. Insulin increases the activity of transporters for glucose uptake into body cells
B. Insulin reduces the concentration of glucose in Jack’s blood
C. Insulin stimulates the breakdown of glycogen to glucose in muscle
i h h l i di hD. Protein phosphorylation mediates the actions of insulin in cells
E I li t it t ith t b i
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E. Insulin acts on its receptors without being transported into the cells
It continues..... “Q1. A strong covalent bond that is between amino acids and functions in maintaining a polypeptide's specific three‐dimensional shape is a (an)
“Q2. Which of the following statements regarding nucleotides is NOT correct? A. Nucleotide monomers are linked together to
build a polynucleotidebuild a polynucleotide
B. Adjacent nucleotides are joined by covalent bonds that form between the –OH group on g pthe 3’ carbon of one nucleotide, and the phosphate on the 5’ carbon on the next
C. Nucleotide polymers have a backbone of sugar‐phosphate units, with nitrogenous bases as appendagesappendages
D. The sequence of bases along a DNA or mRNA polymer is unique for each gene
0% 0% 0%0%0% 1010E. In the DNA double helix, the nitrogenous bases
pair up and form H‐bonds, so that A always pairs with G and T always pairs with C
Back at school, Jack notices that one of his classmates, Max, who recently arrived from Africa, is absent.Max, who recently arrived from Africa, is absent.
Actually, Max is often absent from school after sports y, pevents.
His teacher explains that he is in hospital and has been diagnosed with the disease sickle cell anemia.
Back home at Jack’s placeBack home at Jack s place....
To celebrate Jack’s diagnosis and successful stabilizationTo celebrate Jack s diagnosis and successful stabilization on his insulin regime, his parents took him out for dinner at the local hotel.
His dad had a few beers but thought it OK to drive home. Unfortunately, this happened. Why?
The car was a write off but fortunately injuries to JackThe car was a write‐off, but fortunately injuries to Jack and his parents were limited to minor lacerations.
Jack’s father will definitely be handing the wheel over to his wife next time he has a few drinks when they gohis wife next time he has a few drinks when they go out....
And Jack is getting used to managing his diabetes as part of his daily routine – for life!
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