Prabhakar Singh- IV_SEM-Paper V_MAPLE SYRUP URINE DISEASE, SICKLE CELL ANEMIA

1. TEJASVI NAVADHITAMASTU
“Let our (the teacher and the taught) learning be radiant”
Let our efforts at learning be luminous and filled with joy, and endowed with the force of purpose
Paper XII: CLINICAL AND DIAGNOSTIC BIOCHEMISTRY
Dr. Prabhakar Singh. D.Phil. Biochemistry
Department of Biochemistry, VBSPU, Jaunpur
MAPLE SYRUP URINE DISEASE, SICKLE CELL ANEMIA

2. MAPLE SYRUP URINE DISEASE
This is a metabolic disorder of branched chain amino acids. The urine of the
affected individuals smells like maple syrup or burnt sugar—hence the name as
MAPLE SYRUP URINE DISEASE.
Enzyme defect :Maple syrup urine disease is due to a defect in the enzyme
branched chain D-keto acid dehydrogenase. This causes a blockade in the
conversion of D-keto acids to the respective acyl CoA thioesters. The plasma and
urine concentrations of branched amino acids and their keto acids are highly
elevated. This disease is also known as branched chain ketonuria.
Biochemical complications and symptoms :
1. l Accumulation of branched chain amino acids causes an impairment in
transport and function of other amino acids.
2. l Protein biosynthesis is reduced.
3. l Branched chain amino acids competitively inhibit glutamate dehydrogenase.
4. l The disease results in acidosis, lethargy, convulsions, mental retardation,
coma and, finally, death within one year after birth.

4. Summary of branched chain amino
acid metabolism
–Defect in D-keto acid
dehydrogenase results in maple
syrup urine disease
HMG CoA– E-Hydroxy E-methyl-
glutaryl CoA Valine is glycogenic,
leucine is ketogenic, while isoleucine
is both

5. SICKLE CELL ANEMIA

7. STICKY PATCHES AND FORMATION OF
DEOXYHEMOGLOBIN FIBRES
The sticky patch of one deoxyHbS binds
with the receptor of another deoxyHbS
and this process continuous resulting in
the formation of long aggregate
molecules of deoxyHbS.
Thus, the polymerization of deoxyHbS
molecules leads to long fibrous
recipitates.
These stiff fibres distort the erythrocytes
into a sickle or crescent shape.
The sickled erythrocytes are highly
vulnerable to lysis.
In case of oxyHbS, the complementary
receptor is masked, although the sticky
patch is present. Hence, the molecules of
oxyHbS cannot bind among themselves
or with the molecules of deoxyHbS.
Normal deoxyHbA lacks sticky patches
but
contains receptors. Absence of sticky
patches does not allow the deoxyHbA to
participate in the formation of
aggregates
The substitution of valine for glutamate results in a sticky
patch on the outer surface of E-chains. It is present on oxy-
and deoxyhemoglobin S but absent on HbA. There is a site
or receptor complementary to sticky patch on deoxyHbS.
As explained above, sicklingis due to polymerization of
deoxyHbS. Therefore, if HbS is maintained in the
oxygenated form (or with minimum deoxyHbS), sickling
can be prevented.

10. THALASSEMIAS