Biochemistry

1. AMINO ACID METABOLISM 2
Mrs. Kulkarni Dipali M.
Assistant Professor,
Yash Institute of Pharmacy,
Aurangabad.

2. Catabolism of phenylalanine,tyrosine:
metabolic disorders
(Phenyketonuria, Albinism, alkeptonuria,
tyrosinemia)
Synthesis, significance of biological
substances; 5-HT, melatonin,
dopamine,
noradrenaline,
adrenaline
Catabolism of heme; hyperbilirubinemia
and jaundice

6. 5-HT 5-Hydroxytryptamine
• CNS – As Neurotransmitter
•Biosynthesized from tryptophan
Elimination
• Metabolized by MAO and then
Aldehyde dehydrogenase to form
5-hydroxyindole acetic acid(5-HIAA)
• 5-HIAA is excreted in urine
Functions associated with 5HT pathways are:
Behavioral responses
Feeding behavior
Mood and emotion control
Sleep / wakefulness control
Emetic reflex (esp. chemical triggered)
Control of sensory pathways

7. Biosynthesis
Tryptophan (From diet)
5Hydroxytryptophan
5-Hydroxy tryptamine
5 Hydroxyindole acetaldehyde
5Hydroxyindole acetic acid (5HIAA)
Aromatic L-A.A decardoxylase
Tryptophan hydroxylase
Monoamine oxidase(MAO)

8. Biosynthesis of Melatonin :
Generated from amino acid tryptophan and serotonin
Is made predominantly at night in the pineal gland.
Tryptophan hydroxylase activity where presence in the
mitochondrial increase during darkness
about 2 fold.
Physiological role of melatonin
1-Radical scavenger
2-Sleep
3-Cancer
4-Immune system
5-Other
Melatonin can act as an antioxidant .

10. Catecholamines
• Epinephrine/Adrenaline
• Norepinephrine/Noradrenaline
• Dopamine
• They are found within the CNS, PNS, and
adrenal glands.
Tyrosine is obtained from dietary protein and
is transported from the blood into the brain
• Each step in the formation of catecholamines
depends on a specific enzyme that acts as a
catalyst for that step
• Tyrosine hydroxylase is the rate limiting
enzyme in the pathway -it determines the
overall rate of dopamine and norepinephrine
formation

11. Biosynthesis of Catecholamines

12. Synthesis of dopamine,norepinephrine and epinephrine

13. Regulation of synthesis
• The level of catecholamines within the nerve terminal
– e.g., high catecholamine levels within the nerve
terminal
tend to inhibit tyrosine hydroxylase, serving as a negative
feedback mechanism
• The rate of cell firing
– e.g., when neurons are activated and firing at a high
rate,
such as during stress, tyrosine hydroxylase would be
stimulated
• These elegant mechanisms enable dopaminergic and
noradrenergic neurons to carefully control their rate
of neurotransmitter formation.

14. Catecholamine synthesis, release, and inactivation
• Tyrosine hydroxylase catalyzes the rate-limiting step in
catecholamine synthesis
• Catecholamine formation can be increased ↑ by the
administration of a biochemical precursor (i.e., to be converted into
a particular neurotransmitter) such as – L-DOPA (for the treatment
of Parkinson’s disease)
• Catecholamine formation can be decreased ↓ by the drug, AMPT
(α-methyl-para-tyrosine)
• This compound blocks tyrosine hydroxylase, thus preventing
overall catecholamine synthesis and causing a general depletion of
DA and NE neurotransmitters
• AMPT treatment caused a return of depressive symptoms in
patients who had previously recovered following treatment with
antidepressants that act selectively on the noradrenergic system,
indicating that the depressed patients’ recovery depends on the
maintenance of adequate levels of catecholamines

15. Catabolism of Heme
HEME CATABOLISM: STEPS
1. Destruction of RBC to release Heme
2. Degradation of heme into biliverdin
3. Reduction of biliverdin into bilirubin
4. Transportation of bilirubin in blood
5. Hepatic uptake of bilirubin
6. Conjugation of bilirubin in liver
7. Deconjugation of bilirubin in intestine
8. Excretion
Reticulo endothelial cell
Lysosome
Microsomal system
Cytoplasm
Heme - degraded into bilirubin by reticulo-endothelial cells
(in Microsomal fraction & in cytoplasm sequentially).
• Bilirubin- principal bile pigment - is excreted via liver into intestine

17. Fate of globin
The globin may be reutilized as such for the formation of hemoglobin
or degraded to the individual amino acids.
The amino acids undergo their own metabolism, including
participation in fresh globin synthesis.
One gram of hemoglobin on degradation finally yields about 35 mg
bilirubin.
Approximately 250-350 mg of bilirubin is daily produced in human
adults.
The term bile pigments is used to collectively represent bilirubin and
its derivatives
Bilirubin has greater affinity to bind with MPS

18. Conjugation of Bilirubin in liver
This process is carried out by-
Uridine Di-Phosphate Glucuronosyl Transferase or
(UDP- Glucuronosyl Transferase) enzyme= UGT 1A.
This enzyme is found in endoplasmic reticulum of hepatocytes.
This enzyme transfers Glucuronosyl group of UDP- Glucuronic acid to
COOH group of Propionic acid of bilirubin; process is called
conjugation of Bilirubin.
Bilirubin is converted initially into mono conjugated bilirubin
[Bilirubin Monoglucuronide] and finally into Di-conjugated bilirubin
[Bilirubin Diglucuronide] and render them water soluble

19. Jaundice
Jaundice - clinical sign characterized by yellow discoloration of
sclera,skin & mucosa due to deposition of bilirubin in state of
hyperbilirubinemia.
When bilirubin level exceeds 2mg/dl
Starts to diffuse in tissues & deposited
Yellow discoloration of sclera, mucosa & skin
Jaundice/ Icterus
Bilirubin has greater affinity to bind with MPS.