1. AMINO ACIDS METABOLISM Course: MEDICIMAL CHEMISTRY 1 Course Code: 301

2. Denaturing of Protein Alteration of the protein’s shape and thus functions through the use of – Heat – Acids – Bases – Salts – Mechanical agitation Primary structure is unchanged by denaturing

3. Denaturing of Protein Figure 6.5

4. Protein Digestion: Part 1 Figure 6.6

5. Protein Digestion: Part 2

6. Figure 6.6 Protein Digestion: Part 3

7. Figure 6.6 Protein Digestion: Part 4

8. Amino Acid Absorption Amino acids are absorbed in the small intestine Amino acids are transported to the liver from the intestines via the portal vein In the liver, amino acids are – Used to synthesize new proteins – Converted to energy, glucose, or fat – Released to the bloodstream and transported to cells throughout the body Occasionally proteins are absorbed intact

9. Amino Acid Metabolism Liver metabolizes amino acids, depending on bodily needs Most amino acids are sent into the blood to be picked up and used by the cells – Amino acid pool is limited but has many uses Protein turnover – the continual degradation and synthesizing of protein

10. Amino Acid Pool The amount of free amino acids distributed throughout the body is called amino acid pool Plasma level for most amino acids varies widely throughout the day. It ranges between 4-8 mg/ dl It tends to increase in the fed state and tends to decrease in the post absorptive state Sources of Amino acid pool 1. Dietary protein 2. Breakdown of tissue protein 3. Biosynthesis of nonessential amino acids

11. OVERVIEW OF AMINO ACID METABOLISM ENVIRONMENT ORGANISM Ingested protein Bio- synthesis Protein AMINO ACIDS Nitrogen Carbon skeletons Urea Degradation (required) 1 23 a b Purines Pyrimidines Porphyrins cc Used for energy pyruvate α-ketoglutarate succinyl-CoA fumarate oxaloacetate acetoacetate acetyl CoA (glucogenic)(ketogenic) 11

12. Fate of Amino acid pool 1.Biosynthesis of structural proteins. eg - tissue protiens 2.Biosynthesis of functional proteins. eg- haemoglobin, myoglobin etc. 3.Biosynthesis of small peptides of biological importance. eg- glutathione, endorphins 4. Biosynthesis of non protein nitrogens (NPN) as urea, uric acid, creatine, creatinine and ammonia 5.Catabolism of amino acids to give ammonia and α-keto acids

13. Fate of Amino acid pool Figure 6.7

14. Energy production from Amino Acids GLUCOGENIC AMINO ACIDS – C arbon skeleton can be converted to glucose TCA cycle intermediates or pyruvate (gluconeogensis) KETOGENIC AMINO ACIDS - C arbon skeleton can be converted to ketone bodies

15. GLUCOGENIC / KETOGENIC AMINO ACIDS 15

16. TCA Cycle/ Krebs Cycle/ Citric Acid Cycle

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19. Catabolic pathways of Amino acids 1.Transamination 2.Deamination 3.Transdiamination

21. Transamination reactions

22. Transamination means transfer of amino group from α-amino acid and a new α-keto acid with formation of a new α-amino acid and a new α-keto acid. Liver is the main site of transamination All amino acids can be transaminated except lysine, threonine, proline and hydroxyproline. All transamination reactions are reversible It is catalyzed by aminotransfereses. It needs pyridoxal phosphate as a coenzyme. Examples of transaminase 1.Alanine transaminase 2.Aspartate transaminase 3.Glutamate transaminase

23. Transamination reactions

28. Oxidative deamination

29. Glutamate Dehydrogenase catalyzes a major reaction that effects net removal of N from the amino acid pool. It is one of the few enzymes that can use NAD + or NADP + as e - acceptor.

31. Urea Cycle Most animals convert excess nitrogen to urea, prior to excreting it. Urea is less toxic than ammonia. The Urea Cycle occurs mainly in liver. The 2 nitrogen atoms of urea enter the Urea Cycle as NH 3 (produced mainly via Glutamate Dehydrogenase) The NH 3 and CO2 (carbonyl C) that will be part of urea are incorporated first into carbamoyl phosphate. Function: detoxification of ammonia (prevents hyperammonemia)

32. UREA CYCLE mitochondria cytosol 32