Professional Documents
Culture Documents
Scurvy is a disease characterized by sore and spongy gums, loose teeth, fragile blood vessels,
and poor wound healing. Hydroxylation of proline and lysine is important in the synthesis of collagen.
Hydroxyproline is important in stabilizing the triple helical structure of collagen because it
maximizes interchain hydrogen bond formation. A deficiency in vitamin C leads to lack of
hydroxylation of the two amino acids which now leads to impairment of H-bond formation and
unstable triple helix of the collagen. Additionally, collagen fibrils cannot be cross-linked, greatly
decreasing the tensile strength of the assembled fiber. With this, the connective tissue then becomes
defective, resulting to the above signs and symptoms that characterizes scurvy. Fragile capillary (fragile
blood vessels) can cause subcutaneous extravasation of blood, which explains the multiple hemorrhage
present near the distal end of the patients nail.
***In scurvy, which is due to vitamin C deficiency, hydroxylation of proline residues is decreased, and
an unstable form of collagen is produced. Bones, teeth, blood vessels, and other structures rich in collagen
develop abnormally. Bleeding gums and poor wound healing are often observed.
Reference:
Harvey, R. & Ferrier, D. (2011). Lippincotts Illustrated Reviews: Biochemistry 5th edition.
pp. 20-21, 45-47, 377
Koeppen, B.M. and Stanton, B.A. (2010). Berne and Levy Physiology 6th edition. Mosby, Inc.
(Elsevier): Canada
page 38
CASE 3
1. Explain the difference between human insulin and Humalog mix 75/25 as to structure and
pharmacokinetics.
Chemical Structure:
Insulin contains 51 amino acids arranged in 2 polypeptide chains, Chain A and Chain B.
Chain A is made up of 21 amino acids, while Chain B consists of 30 amino acids.
Residues A7 to B7 and A20 to B19 of chains A and B are covalently bonded by disulfide
bridges.
Structure of human proinsulin (C-peptide plus A and B chains) and insulin. Insulin is shown as the
shaded (orange color) peptide chains, A and B. In insulin lispro, the proline and lysine, at B28 and B29
respectively, have been reversed.
Insulin lispro, the first monomeric insulin analog to be marketed, is produced by
recombinant technology wherein two amino acids near the carboxyl terminal of the B
chain have been reversed in position: Proline at position B28 has been moved to B29,
and lysine at position B29 has been moved to B28.
The Humalog mix 75/25 is a mixture of insulin lispro solution, a rapid-acting blood
glucose-lowering agent and insulin lispro protamine suspension, an intermediate-acting
blood glucose-lowering agent.
Pharmacokinetics:
ONSET
PEAK
DURATION
30 min 1 hour
2 3 hours
4 6 hours
b. 75/25 Humalog
1.5 hours
Up to 10 16 hours
REFERENCE:
Katzung, B. (2012). Basic & Clinical Pharmacology. 12th ed. New York: McGraw-Hill Medical p. 744
Brunton, L. (2011). Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th ed.
McGraw-Hill Professional. pp. 1250-1251)
CASE 4:
1. What is the most likely diagnosis? Justify your answer.
Based on the description of the pain that shes experiencing, the patient most likely has sickle
cell disease; which is common among the people with African-American descent.
The pain that the patient is experiencing is due to anoxia because the sickle cells block the flow
of blood into the capillaries, thus, there is interruption in the oxygen supply which explains her fatigue
and the paleness of her mucosal membranes. Her condition was triggered by the urinary tract infection
she is currently experiencing (based on the results of her urinalysis, and white blood cell count, frequent
and burning urination)
2. Explain the biochemical basis for the patients condition.
Single amino acid substitution on the hemoglobin chain. A molecule of HbS contains 2 normal
-globin chains and 2 mutant -globin chains, in which glutamate at the sixth position has been replaced
with valine.
*** Hemoglobinopathies result from mutations that produce alterations in the structure of hemoglobin. There
are many described hemoglobinopathies. One common mutation results in sickle cell anemia, in which the
chain of haemoglobin contains a valine rather than a glutamate at position 6 (designated as E6V, using the
single-letter codes for the amino acids. E6V means that the glutamate [E] at position 6 in the amino acid chain
[where the amino terminal is amino acid number 1] has been replaced by a valine [V]). Thus, in the mutant
hemoglobin (HbS), a hydrophobic amino acid replaces an amino acid with a negative charge. This change
allows deoxygenated molecules of HbS to polymerize. Red blood cells that contain large complexes of HbS
molecules can assume a sickle shape. These cells undergo hemolysis, and anemia results. Painful vasoocclusive crises also occur, and end-organ damage may result.
References:
Denise R. Ferrier, Lippincott's Illustrated Reviews Biochemistry, 6th edition, pages 35-37