Dr.

Alleyne Review for RESP Biochemistry

Sickle-cell:
Sickle cell anaemia....caused by point-mutation glutamic acid (negative charge: -COO
-
) replaced by
valine (hydrophobic) at 6
th
position hydrophobic interactions yields Hb sticking together (normally the
2 negative glutamates would have repelled)
What could have glutamate been replaced with, that would not yield sickle-cell symptoms/signs?
Aspartate......same -COO
-
and thus same repulsive negative interactions between Hb
If glutamic acid had been replaced with lysine, what would be the result? No change (no sickle-cell
symptoms) as lysine is positively charged (-NH
3
+
).....thus similar repulsive forces between like charges
What could glutamic acid be replaced with that would present similarly as sickle-cell? Any hydrophobic
amino acid......e.g. leucine or isoleucine
Thalassemia:
Genetic disease affecting globin chains in Hb.
Consider alpha-thalassemia: affects alpha-globin chain......loss of part/whole alpha chain

-
thlassemia: loss of part of alpha chain (minus is small piece)

o
thalassemia: loss of whole alpha chain (nought is whole)
Consider on an electrophoresis gel: Hb gives 2 bands....alpha and beta

-
thlassemia: have 2 bands still and band relating to alpha chain would move farther....alpha chain lose
small piece, thus lighter and can travel farther

o
thalassemia: have only 1 band (beta chain band) as no alpha chain
Smoking
Have digestive enzymes in lungs too....trypsin, chymotrypsin, elastase (produced by
neutrophils/macrophages in inflammatory response to cigarette smoke). These enzymes break-down
any unwanted proteins that reach lungs/alveoli. However, if they are not stopped they will continue to
break-down even the lung tissue and lead to emphysema. The molecule that inhibits these enzymes and
prevents the uncontrolled destruction of lung tissue is 1- antitrypsin.
Smoking alternation of 1- antitrypsin via some mechanism (smoking oxidises the methionine residue
of 1-antitrypsin to methionine sulfoxide and inactivates it. The methionine residue is the one that
normally binds to the digestive enzymes and inhibits them) no inhibition of digestive enzymes
unopposed destruction of lung tissue emphysema