1. Biotransformation Saiesh phaldesai 1st year M.pharma Pharmaceutics
By-
Saiesh phaldesai
1st year M.pharma
Pharmaceutics
Srinivas college of pharmacy
mangalore

2. Phase II reactions CONJUGATION WITH GLUCORDIC ACID
CONJUGATION WITH SULPHATE MOIETIES
CONJUGATION WITH ALPHA AMINO ACIDS
CONJUGATION WITH GLUTATHIONE AND MERCAPTOPURIC ACID
ACETYLATION
METHYLATION
Miscellaneous Conjugation Reactions

3. CHARACTERISTICS: They are simple endogenous molecules.
They are large molecular size.
They are polar or ionic substance so to render the substrate soluble.

4. CONJUGATION WITH GLUCORDIC ACID
Glucuronide formation occurs in 2 steps:-
Synthesis of an activated coenzyme uridine-5’- diphospho -alpha-D- glucuronic acid (UDPGA) from UDP- glucose (UDPG). The coenzyme UDPGA acts as the donor of glucuronic acid. UDPG is synthesized by interaction of alpha-D Glucose-1-Phosphate with uridine triphosphate (UTP).
Transfer of the glucuronyl moiety from UDPGA to the substrate RxH in presence of enzyme UDP- glucuronyl transferase to form the conjugate. In this step, the alpha- configuration of glucuronic acid undergoes inversion and thus, the resulting product is beta-D-glucuronide.

5. STEPS INVOLVED ARE:

6. CONJUGATION WITH SULPHATE MOIETIES
Synthesis of an activated coenzyme 3’-phosphoadenosine-5’-phosphosulfate(PAPS) which acts as a donor of sulfate to the substrate. This also occurs in two steps- an initial interaction between the sulfate and the adenosine triphosphate (ATP) to yield adenosine-5’-phosphosulfate (APS) followed by activation of latter to PAPS.
Transfer of sulfte group from PAPS to the substrate RXH in presence of enzyme sulfotransferase and subsequent liberatioj of 3’- phosphoadenosine-5’-phosphate(PAP).

7. THE STEPS INVOVLED ARE:

8. CONJUGATION WITH ALPHA AMINO ACIDS
1 Activation of carboxylic acid drug substrate with ATP and coenzyme A (CoA) to form an acyl CoA intermediate. Thus, the reaction is a contrast of glucuronidation and sulfation where the donor coenzyme is activated and not the substrate.
2 Acylation of the alpha- amino acid by the acyl CoA in presence of enzyme N-acyl transferase.

9. THE REACTION IS SUMMARIZED BELOW :

10. CONJUGATION WITH GLUTATHIONE AND MERCAPTURIC ACID FORMATION

11. CONJUGATION WITH GLUTATHIONE AND MERCAPTURIC ACID FORMATION

12. ACETYLATION
The enzyme involved is the nonmicrosomal N-acetyl transferase. Acetylation is an important metabolic pathway for drugs containing primary amino groups.

13. METHYLATION
1.Synthesis of an activated coenzyme s-adenosyl methionine, the donor of methyl group, from L- methionine and ATP
2. Transfer of the methyl group from Sam to the substrate in presence of nonmicrosomal enzme methyl transferase

14. Miscellaneous Conjugation Reactions
Conjugation of cyanide:-
Conjugation of cyanide ion involves transfer of sulfur atom from thiosulfate to the cyanide ion in presence of enzyme rhodanese to form inactive thiocyanate.
Conjugation with Ribose:-
Endogenous pruine and pyrimidine bases conjugate with ribose to form nucleotides.
Conjugation with Taurine:-
Taurine, a beta-amino sulfonic acid, conjugates the endogenous bile acids to produce components of bile

15. Factor affection of Biotransformation of Drug
The Therapeutic efficacy, Toxicity and Biological half life of drug depends on metabolic rate.
And the factor that influence metabolic rate are:
1) Physico chemicval property of drug.
2) chemical factors.
a. Induction of drug metabolizing enzyme.
b. Inhibition of drug metabolizing enzyme
c. Environmental chemicals.
3) Biological factors.
A. Species differences.
B.strain differences.
C. Sex differences.
D.Age.
E. Diet.
F. Altered pharmacologic factors.
i Pregnancy.
ii Hormonal imbalance.
Iii Disease state.
G. Temporal factors.
I Circadian rhythm.

16. REFERENCES
1 Biopharmaceutics & pharmacokinetics. A.treatise, D.M.Brahmankar & S.B. Jaiswal, Vallabh Prakashan, P.No Biopharmaceutics & clinical pharmacokinetics by Milo Giberldi, 4th edition, Philadelphis, Leu and febiger, P.No Text book of Biopharmaceutics & pharmacokinetics, Dr.Shobha Rani R. Hiremath, P.No

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