Role in Disease
Disorders of this protein include alpha 1-antitrypsin deficiency, an autosomal recessive hereditary disorder in which a deficiency of alpha 1-antitrypsin leads to a chronic uninhibited tissue breakdown. This causes the degradation especially of lung tissue, and eventually leads to characteristic manifestations of pulmonary emphysema. Evidence has shown that cigarette smoke can lead to oxidation of methionine 358 of α1-antitrypsin (382 in the pre-processed form containing the 24 amino acid signal peptide), a residue essential for binding elastase; this is thought to be one of the primary mechanisms by which cigarette smoking (or second-hand smoke) can lead to emphysema. Because A1AT is expressed in the liver, certain mutations in the gene encoding the protein can cause misfolding and impaired secretion, which can lead to liver cirrhosis.
An extremely rare form of Pi, termed PiPittsburgh, functions as an antithrombin (a related serpin), due to a mutation (Met358Arg). One person with this mutation has been reported to have died of a lethal bleeding diathesis.
Liver biopsy will show abundant PAS-positive globules within periportal hepatocytes.
Read more about this topic: Alpha 1-antitrypsin
Famous quotes containing the words role in, role and/or disease:
“Certainly parents play a crucial role in the lives of individuals who are intellectually gifted or creatively talented. But this role is not one of active instruction, of teaching children skills,... rather, it is support and encouragement parents give children and the intellectual climate that they create in the home which seem to be the critical factors.”
—David Elkind (20th century)
“But however the forms of family life have changed and the number expanded, the role of the family has remained constant and it continues to be the major institution through which children pass en route to adulthood.”
—Bernice Weissbourd (20th century)
“His poor self,
A dedicated beggar to the air,
With his disease of all-shunned poverty,
Walks, like contempt, alone.”
—William Shakespeare (1564–1616)