Valine, Ieucine & isoleucine are the branched
chain & essential amino acids.
Valine (Val) is glucogenic amino acid.
Leucine (Leu) is ketogenic amino acid.
Isoleucine (Ile) is both ketogenic & glucogenic
These amino acids serve as an alternate
source of fuel for the brain especially under
conditions of starvation.
The first three metabolic reactions are
common to the branched chain amino acids.
2. Oxidative decarboxylation
The three amino acids undergo a reversible
transamination to form their respective keto
α-Keto acid dehydrogenase is a complex
It is comparable in function to PDH complex
& requires 5 coenzymes - TPP, lipoamide,
FAD, coenzyme A & NAD+.
α-Keto acid dehydrogenase catalyses
oxidative decarboxylation of the keto acids
to the corresponding acyl CoA thioesters.
This is a regulatory enzyme.
The dehydrogenation is similar to that in
fatty acid oxidation.
FAD is the coenzyme & there is an
incorporation of a double bond.
There are two enzymes responsible for
The branched chain amino acids diverges &
takes independent routes.
Valine is converted to propionyl CoA, a
precursor for glucose.
Leucine produces acetyl CoA & acetoacetate,
the substrates for fatty acid synthesis.
Isoleucine is degraded to propionyl CoA &
Valine is glycogenic & leucine is ketogenic.
Isoleucine is both glycogenic & ketogenic.
Acyl CoA Dehydrogenase
Methylacrylyl CoA Triglyl CoA
Maple syrup urine disease:
The urine of the affected individuals smells
like maple syrup or burnt sugar.
Enzyme defect: Branched chain α-keto acid
This causes a blockade in the conversion of
α-keto acids to the respective acyl CoA
The plasma & urine concentrations of
branched amino acids & their keto acids are
This disease is also known as branched chain
Accumulation of branched chain amino acids
causes an impairment in transport & function
of other amino acids.
Protein biosynthesis is reduced.
Branched chain amino acids competitively
inhibit glutamate dehydrogenase.
The disease results in acidosis, lethargy,
convulsions, mental retardation, coma &
death within one year after birth.
Urine contains branched chain keto acids,
valine, leucine & isoleucine.
Rothera's test is positive.
Diagnosis depends on enzyme analysis.
Diagnosis should be done prior to 1 week
Diet low in branched chain amino acids.
This is a less severe variant form of maple
syrup urine disease.
Enzyme defect:α-keto acid dehydrogenase.
There is an impairment & no total blockade
in the conversion of α-keto acids to their
respective acyl CoA thioesters.
Careful diet planning is adequate.
This is a specific inborn error of leucine
Enzyme defect: Enzyme isovaleryl CoA
The conversion of isovaleryl CoA to
methylcrotonyl CoA is impaired.
The excretion of isovalerate is high in urine.
The affected individuals exhibit a 'cheesy'
odor in the breath & body fluids.
The symptoms include acidosis & mild mental
This inborn error is characterized by
increased plasma concentration of valine
while leucine & isoleucine levels remain
The transamination of valine alone is
Textbook of Biochemistry-U Satyanarayana
Textbook of Biochemistry-DM Vasudevan