Metabolism of tryptophan

• An aromatic amino acids

• Indole ring containing amino acid
• α-amino β- indole propionic acid
• Neutral amino acid
• Essential amino acids
• Both glucogenic and ketogenic
Biologically important compound derived from
tryptophan
Metabolism of Tryptophan

Metabolism is divided into

• Kynurenine pathway
• Serotonin pathway
Kynurenine pathway
• Mainly takes place in liver
• Through this pathway tryptophan is oxidized into :
Alanine
Acetyl CoA
Niacin Co-enzyme (NAD+,NADP+)
 Serotonin pathway
• Serotonin or 5-hydroxytryptamine (5HT)
• It is a neurotransmitter
• Normally about 1% of tryptophan is converted into serotonin and 99%
are metabolized to form alanine ,acetyl CoA and niacin
• Serotonin is widely distributed in the body
• In mammals largest amount is synthesized in the intestinal cells
Functions of serotonin
• Excitatory neurotransmitter in brain
• It is closely involved in the regulation of cerebral activity
• Potent vasoconstrictor and causes smooth muscle
contractions in bronchioles and arterioles
• Causes platelet aggregation
• Causes peristalsis, peptide hormone release in GI tract
• Serotonin controls sleep, behavioural pattern, blood pressure
and body temperature
Carcinoid syndrome
• Serotonin is produced by Argentaffin cells of GI tract
• These cells undergo uncontrolled growth and lead to carcinoid tumour
• Flushing, sweating, Bronchoconstriction, Diarrhoea, heart failure
• Tryptophan to niacin conversion is decreased– pallegra like
symptoms(60% tryptophan is channeled towards formation)
• Metabolite of serotonin 5HIAA in urine is increased
 Melatonin
• Produced by pineal gland
• Synthesis is regulated by light dark cycle
• Functions as neurotransmitter
• Modulates circadian rhythm
• Maintain sleep wake cycle
• Regulates reproductive function
 Hartnup’s disease
• First described in family of Hartnup
• Autosomal recessive disorder
• Intestinal and renal transport of tryptophan and other neutral amino acids
(Ala,Ser,Val,His) are decreased
• The net outcome – low levels of these a.a. in blood and their excretion in
urine is increased
• Diagnosis –increased level in urine
• Decreased plasma tryptophan level
Hartnup’s disease cont……
• Clinical symptoms include dermatitis, ataxia, mental retardation
,neutral amino aciduria
• Pellegra like and neurological symptoms due to tryptophan
• Impairment in the synthesis of NAD+ and serotonin from tryptophan
Metabolism of sulphur containing amino
acid
• L-methionine –essential amino acid
• L-Cysteine
• L-cystine
• Methionine ,cysteine and cystine are the principal sources of Sulphur in
the body
• Methionine is essential a.a.
• Cysteine can be synthesized in the body from methionine
• Other sources of S in body is thiamine ,lipoic acid and
biotin
Compounds formed from methionine

• Protein
• Glucose
• Cysteine
• S-adenosyl methionine
Fate of L-methionine
• Stage 1- Activation of methionine into S adenosyl methionine and its
demethylation to form L-homocysteine
• Stage 2 – Conversion of L-homocysteine to L-homoserine
• Stage 3 – Degradation of homoserine to end products L-propionyl-
CoA and α-amino butyrate
 Active methionine/adenylation of
methionine
• Chemically called as S-adenosyl methionine
• Activation of methionine is in presence of ATP (catalyzed by an enzyme ,called
L-methionine adenosyl transferase -MAT)
• Requires presence of Mg ion and G-SH
• ATP donates the entire adenosine moiety to methionine and looses 3 molecules
of phosphate
• In methionine ,the thio-ether linkage (C-S-C) is very stable but in SAM CH3
group forms a high energy bond with sulphur and methyl group becomes
labile and easily transferred to the acceptor
 Transmethylation reaction

Transfer of methyl group –CH3 from active methionine to an acceptor is known

as Transmethylation reaction
In SAM due to presence of high energy bond ,the methyl group is labile and
may be transferred easily to other acceptors
Importance of Transmethylation reaction

• Many compounds in our body become functional or active only after

methylation
• Methylated protein is less degraded
Fate of homocysteine which is formed after transmethylation reaction

• From S-adenosyl homocysteine ,the adenosyl group is removed to form

homocysteine (Homologous with cysteine )
• Homocysteine again converted into methionine by addition of methyl
group donated from one carbon pool with the help of Vit B12
• Homocysteine degradation – Homocysteine condenses with serine to form
cystathionine (by enzyme cystathionine beta synthase in presence of
Pyridoxal phosphate )
• Cystathionine is hydrolyzed to form cysteine and homoserine (enzyme –
cystathionase )
• Homoserine is deaminated and then decarboxylated to propionylCoA
• Propionyl CoA is changed into succinyl CoA and enters TCA cycle
Inborn errors of metabolism of Sulfur containing amino
acids
• Cystinuria
• Cystinosis
• Homocystinuria type I
• Homocystinuria II
• Homocystinuria III
• Cystathionuria