A 44-year-old man is evaluated due to progressive dyspnea over the past several years. The patient has no associated chest pain or palpitations. Physical examination shows a prolonged expiratory phase without wheezes or rhonchi. CT scan of the chest demonstrates bilateral lower lobe-predominant emphysema. Further testing reveals that the patient has a protease inhibitor deficiency, which has led to increased elastin fiber breakdown. Elastin fibers within alveolar walls normally allow the lung to stretch during active inspiration and recoil during passive expiration. Which of the following most likely contributes to this property of elastin?

Question

A 44-year-old man is evaluated due to progressive dyspnea over the past several years.  The patient has no associated chest pain or palpitations.  Physical examination shows a prolonged expiratory phase without wheezes or rhonchi.  CT scan of the chest demonstrates bilateral lower lobe-predominant emphysema.  Further testing reveals that the patient has a protease inhibitor deficiency, which has led to increased elastin fiber breakdown.  Elastin fibers within alveolar walls normally allow the lung to stretch during active inspiration and recoil during passive expiration.  Which of the following most likely contributes to this property of elastin?

Quizplus · Accepted Answer

11ec160b_36f5_9c1d_9249_95030b4210fc_MD0001_00 This patient's emphysema is likely due to alpha-1 antitrypsin deficiency. Neutrophil-secreted elastase is an endogenous proteolytic enzyme that hydrolyzes elastin within alveolar walls. The liver synthesizes alpha-1 antitrypsin, a protein that inhibits neutrophil elastase and prevents alveolar wall degradation, particularly in the lower airways. Patients with alpha-1 antitrypsin deficiency consequently develop excessive alveolar elastin degradation, which clinically manifests with early-onset, lower lobe-predominant emphysema. Elastin is a fibrous connective tissue protein that provides elasticity to the skin, blood vessels, and pulmonary alveoli. The fibers can stretch to several times their length and recoil back to their original size once stretching forces are withdrawn. Elastin assembly is closely related to that of collagen. Similar to collagen, elastin is synthesized as a large polypeptide precursor (tropoelastin) composed of about 700, mostly nonpolar, amino acids (eg, glycine, alanine, valine) (Choice D). Elastin also contains proline and lysine residues; however, in contrast to those found in collagen, few of these amino acids are hydroxylated (Choice C). After tropoelastin is formed, it is secreted into the extracellular space where it interacts with microfibrils (fibrillin) that function as a scaffold. Next, lysyl oxidase, a copper-dependent enzyme, oxidatively deaminates some of the lysine residues of tropoelastin, facilitating the formation of desmosine cross-links between neighboring polypeptides that hold the elastin molecules together. These cross-links, along with the high content of nonpolar (hydrophobic) amino acids, account for the rubber-like properties of elastin. (Choices A and B) Disulfide bridges are formed during collagen, not elastin, synthesis. After post-translational hydroxylation and glycosylation of procollagen molecules, disulfide bond formation between the C-terminal propeptide regions of 3 alpha chains brings the chains into a favorable alignment for triple helix assembly. Educational objective: The rubber-like properties of elastin are due to high content of nonpolar (hydrophobic) amino acids and extensive cross-linking between elastin monomers facilitated by lysyl oxidase. Patients with alpha-1 antitrypsin deficiency can develop early-onset, lower lobe-predominant emphysema due to excessive alveolar elastin degradation. __________ References: Elastin metabolism and chemistry: potential roles in lung development and structure. (http://www.ncbi.nlm.nih.gov/pubmed/6376098)

A 44-Year-Old Man Is Evaluated Due to Progressive Dyspnea Over