For All Medical & Non Medical Students

1. Metabolism of
Branched Chain Amino Acids
By
N. Santhosh Kumar
Asst.Professor
Department of Biochemistry
SIMS&RH, Tumkur

2. Branched chain amino acid
Neutral, Aliphatic, nutritionally essential amino acid
Metabolically
glucogenic a.a’s
Metabolically glucogenic
& Ketogenic a.a’s
Metabolically
Ketogenic a.a’s

3. Catabolism
of
Branched Chain Amino Acids

4. 1st common reaction

5. 2nd common reaction
TPP, FAD,
Lipoic acid

6. 3rd common reaction

7. Valine, Leucine Isoleucine

9. Disorders of BCAAs
Maple syrup urine
disease (MSUD)

10. Rare, genetic defect 1:1 lakh live births
Defect of Branched chain -keto acid dehydrogenase
Blockade in the conversion of -keto acids to the
respective Acyl CoA thioesters

11. conc of BCAAs and their keto acids are highly elevated
in Plasma &urine
Accumulation of BCAAs causes an impairment in
transport and function of other amino acids
reduced Protein biosynthesis

12. Vomiting, dehydration, metabolic acidosis
Complications & Symptoms
Urine of the affected individuals smells like burnt
sugar
If not treated, lethargy, convulsions, mental retardation,
coma and death within 1 year after birth

13. FeCl3 test, Rothera's test
Dinitrophenyl hydrazine (DNPH) test (+ve)
Low diet of branched chain amino acid &
high dose of Thiamine (B1)
Diagnosis
Treatment

14. Case Base Question-1
A neonate’s urine sample was sent to laboratory for suspected an
inborn error of the metabolism. Mother of baby gave history of
poor feeding and frequent episodes of vomiting. The urine sample
had burnt sugar smell. Rothera’s test was positive
A: Identify the inborn error of metabolism?
B:Mention the enzyme defect in above condition?
C: What are the laboratory findings in urine?
D: Rothera’s test positive indicates the presence of which
pathological constituent in urine?

15. A child presented to emergency with severe vomiting,
dehydration and fever. History revealed that child was born
normal but from last few months was noted to develop
progressive mental retardation. The urine of patient had smell
of burnt sugar. Urine analysis showed increased levels of
branched chain keto acids and Rothera's test also positive.
Q: a) What is the probable diagnosis?
b) Mention the biochemical defect.
c) Name the amino acids likely to be excreted in urine.
d) Which vitamin is useful in treatment of this condition?
Case Base Question-2

16. Solve the MCQs
In maple syrup urine disease, which of the following compounds is
accumulated ?
a. Homogentiste b. Methylmalonyl CoA
c. Branched chain α-keto acids d. Homocysteine
Defect of Branched chain α-keto acid dehydrogenase leads to
a. Maple syrup urine disease b. Albinism
c. Hartnup disease d. Phenylketonuria
An inborn error, maple syrup urine disease is due to deficiency of the
enzyme
a. Glycinase b. Branched chain amino transferase
c. Acyl CoA dehydrogenase d. α-keto acid dehydrogenase
One of the following amino acids give rise to α-keto acids that accumulate
in the urine in maple syrup urine disease
a. Phenylalanine b. Valine
c. Lysine d. tyrosine

17. Intermittent branched
chain ketonuria
Isovaleric acidemia

18. Excretion high
in urine
Specific inborn
error of leucine
metabolism.
Defective enzyme
isovaleryl-CoA DH
Cheesy odor in the
breath and body
fluids.
Symptoms include
acidosis & mild
mental retardation.

19. Metabolism of
Hydroxyl group containing
amino acids

20. Nonessential &
Glucogenic amino
acid
Essential &
Glucogenic amino
acid

21. Metabolism of Serine

22. Sources
Serine
Glycine
Phospholipids
(Phosphatidylserine)
Alanine +
hydroxypyruvate
Catabolism
Glycine (in humans)
Pyruvate + NH4
+
Deamination
(Serine dehydratase )
serine
OH-methyl Transferase

23. Metabolic fate of Serine
• Donates one carbon group (methyleneTHF) to the one C- pool
• Formation of cysteine
• Synthesis of phospholipids (Phosphatidyl serine)
• Spingosine (sphingolipid from serine & palmitoyl CoA)
• Serine analogues are used as anticancer drug (Azaserine) &
antituberculous drug (Cycloserine)

24. • Forms the active catalytic residue of many enzymes
- Serine proteases eg: trypsin & coagulation factors.
• Involves signal transduction (Serine and threonine kinase)
• Serine decarboxylated to ethanolamine by PLP (cephalin)
• it forms choline (involved acetylcholine-neurotransmitter)

25. Metabolism of Threonine
(Essential & Glucogenic amino acid)

26. Catabolism
Propionyl CoA
Oxidatively decarboxylation
PLP
Succinyl CoA
TCA cycle
Methylmalonyl CoA
Biotin
B12
Oxidative deamination

27. THREONINE
OH group of threonine in protein
serves to provide a site for
phosphorylation
Threonine aldolase
Acetate
Dehydrogenase
Acetyl CoA
Thiokinase

28. Thank You