METABOLISM OF PROTEINS AND AMINO ACIDS

Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids (anabolism), and the breakdown of proteins by catabolism. ... In humans, non-essential amino acids are synthesized from intermediates in major metabolic pathways such as the Citric Acid Cycle.

1. METABOLISM OF PROTEINS AND AMINO ACIDS Prepared By: Rabia Khan Baber Course Title : Biochemistry

2. AIMS AND OBJECTIVES OF CLASS Introduction to amino acid pool Essential and nonessential amino acids What is amino acid metabolism Where does amino acid metabolism occur ? The general ways of amino acids degradation Outline of amino acid degradation T ransamination Specific transaminases Role of pyridoxal phosphate

3. AIMS AND OBJECTIVES OF CLASS What is deamination ? Why does deamination occur? Types of deamination Importance of oxidative deamination Types of non oxidative deamnation Difference between oxidative and non-oxidative deamination

4. AIMS AND OBJECTIVES OF CLASS What is decarboxylation ? What are biogenic amines? Importance of biogenic amines Classification of biogenic amines, their importance and functions

5. AMINO ACID POOL The amino acids available for protein synthesis at any given time; the liver regulates the blood level of amino acids based on tissue needs and converts excess amino acids to carbohydrates for energy production. The " Amino Acid Pool" is a grand mixture of amino acids available in the cell derived from dietary sources or the degradation of protein. Since proteins and amino acids are not stored in the body, there is a constant turnover of protein.

6. NONESSENTIAL VS. ESSENTIAL AMINO ACIDS Nonessential AA Amino acids that can be synthesized by the body Alanine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine, Tyrosine Essential AA Amino acids that can not be synthesized by the body Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine*, Phenylalanine*, Threonine, Tryptophan, Valine

7. WHERE DOES AMINO ACID METABOLISM OCCUR ? The small intestines, liver, kidneys, and muscle are organs that play an essential role in amino acid metabolism. The main role of each is given as follows. Intestine: Amino acids from protein digestion are absorbed in the small intestine . Liver : The catabolism of amino acids, except those with branched chains, starts in the live r. Kidney : Kidney captures glutamine released from muscles.

8. AMINO ACID METABOLISM The general ways of amino acids degradation : 1. Transamination ​ 2 . Deamination 3. Decarboxylation

9. OUTLINE OF AMINO ACID DEGRADATION All amino acids contain at least one nitrogen atom, which forms their α-amino group; several amino acids contain additional nitrogen atoms in their side chains. Some nitrogen is used in biosynthesis, for example of nucleotides, but most of it is surplus and must be eliminated. To this end, the liver incorporates it into urea, which is released into the bloodstream and excreted by the kidneys. Removal of nitrogen is typically an early step in the degradation and leaves behind the carbon skeleton. The structure of the latter is different for each amino acid, and accordingly each amino acid has its own specific pathway of degradation.

10. CONT.. The liver is the major site of degradation for most amino acids, but muscle and kidney dominate the degradation of specific ones Nitrogen is removed from the carbon skeleton and transferred to α-ketoglutarate, which yields glutamate The carbon skeletons are converted to intermediates of the mainstream carbon oxidation pathways via specific adapter pathways Surplus nitrogen is removed from glutamate, incorporated into urea, and excreted

11. TRANSAMINATION One of the central reactions of the amino acid metabolism is The process of transamination occurs through aminotransferase enzymes which can be specific for an amino acid or can cater to several amino acids that are similar in their chemical compositions. Amino acid that is currently not needed can be transformed into another amino acid that is currently needed. The reallocation of the amino group occurs via an alpha-keto acid, which has an analogous structure to alpha-amino acids. Alpha-keto acids only differ from alpha-amino acids in having a keto group, instead of an amino group.

12. α- a mino acid (Donor) α- ketoacid (Recipient) New amino acid New keto acid

13. Transamination turns the alpha-keto acid into a new amino acid available for metabolism. The responsible enzyme is called aminotransferase (or transaminase). The aminotransferase, however, needs an assistant to do its work: the pyridoxal phosphate (PLP). This is a coenzyme produced out of vitamin B6 (pyridoxine) by phosphorylation. PLP has an aldehyde group (H-C=O) that reacts in the transamination with the amino group of the amino acid (with the elimination of H2O). With this, a Schiff base (R-NH2) is formed. This reaction destabilizes the amino acid and the hydrogen atom starts to migrate which, in turn, leads to a shift of the double bond and ketamine (R-C=O) emerges from the former aldimine (H-C=O ). Then, water is added across this double bond which concludes the formation of the alpha-keto acid. PLP is reduced to PMP (pyridoxamine phosphate). The reverse reaction is also a common variation for generating another amino acid: pyridoxamine phosphate reacts with another alpha-keto acid and PLP is reconstituted.

14. SPECIFIC TRANSAMINASES Specific transaminases are clinically important because they use specific amino acid and specific ketoacid . i. Aspartate transaminase ii. Alanine transaminase

15. Aspartate transaminase (ASAT) ; Also known as Aspartate amino transferase . The ASAT transfers the amino group from aspartate to alpha-ketoglutarate, forming oxaloacetate and glutamate. Alanine transaminase (ALT) ; Also known as Alanine amino transferase. ALAT catalyzes the transfer of an amino group from alanine to alpha-ketoglutarate, forming pyruvate and glutamate

16. ROLE OF PYRIDOXAL PHOSPHATE IN TRANSAMINATION The pyridoxal phosphate, is the most important coenzyme in the amino acid metabolism. PLP is the biologically active form of pyridoxal, the aldehyde form of vitamin B6. Vitamin B6 also appears as amine (pyridoxamine) and alcohol (pyridoxine). The derivatives of vitamin B6 can be converted into each other. They are ingested and can be found in animal-based food (pyridoxal and pyridoxine), as well as in vegetable-based food (pyridoxine ). Wheat germs are relatively rich in vitamin B6. PLP as a coenzyme is involved in the amino acid metabolism in the reactions of transamination, decarboxylation and deamination.

17. CONCLUSION Transamination is a biochemical reaction undergone by amino acids. It is involved in the exchange of an amine group with a keto group. Transamination reactions are responsible for the synthesis of nonessential amino acids. In comparison, deamination is a biochemical reaction responsible for the breakdown of excess proteins in the liver. It involves the removal of the amine group from amino acids, releasing ammonia. Therefore, the main difference between transamination and deamination is the type of biochemical reaction and importance.

18. DEAMINATION When an oversupply of nitrogen in the form of amino acids exists, it needs to be disposed of somewhere in the body. Deamination is the process that carries out this breakdown of amino acids. However, this process releases free cytotoxic ammonia which has to be quickly metabolized to urea. This urea synthesis, which requires a lot of energy, takes place in the liver. For this to happen, the excess nitrogen needs to be transported from the periphery to the liver.

19. DEAMINATION OF CYTOSINE TO URACIL  Deamination is the removal of the amine group as ammonia (NH3)

20. WHY DOES DEAMINATION OCCUR ? Deamination occurs when an excess in protein is consumed, resulting in the removal of an amine group, which is then converted into ammonia and expelled via urination. This deamination process allows the body to convert excess amino acids into usable by-products.

21. The potential problem with deamination is that too much ammonia is toxic, causing a condition known as hyperammonemia . The symptoms of this condition are shown below

22. Our body has a method to safely package ammonia in a less toxic form to be excreted. This safer compound is urea, which is produced by the liver using 2 molecules of ammonia (NH3) and 1 molecule of carbon dioxide (CO2). Most urea is then secreted from the liver and incorporated into urine in the kidney to be excreted from the body

23. TYPES OF DEAMINATION There are two types of deamination. i. OXIDATIVE DEAMINATION ii. NON-OXIDATIVE DEAMINATION

24. OXIDATIVE DEAMINATION Oxidative deamination is the process of removal of an amine group from a molecule via oxidation. This type of reactions largely occurs in liver and kidney. It involves the generation of alpha-keto acids and some other oxidized products from amine groups. This reaction is very important in the catabolism of amino acids. It forms a catabolized product from amino acids. the byproduct of this reaction is ammonia which is a toxic byproduct. Here, the amine group converts into ammonia. And then, this ammonia converts into urea and excreted from our body.

25. Most of the times, glutamic acid or glutamate is the main reactant of this type of reactions. Because, glutamic acid is the end product of many transamination reactions that take place in our cells. Furthermore, the enzyme involved in this reaction is glutamate dehydrogenase. This enzyme catalyzes the transfer of an amino group to an alpha-keto acid group. Also, there is another enzyme that involves in this type of reactions. It is the monoamine oxidase enzyme that catalyzes the deamination via the addition of oxygen.

26. IMPORTANCE OF OXIDATIVE DEAMINATION Central Role for Glutamic Acid: Apparently most amino acids may be deaminated but this is a significant reaction only for glutamic acid. If this is true, then how are the other amino acids deaminated? The answer is that a combination of transamination and deamination of glutamic acid occurs which is a recycling type of reaction for glutamic acid. The original amino acid loses its amine group in the process .

27. NON OXIDATIVE DEAMNATION Non-oxidative deamination is the process of removal of an amine group from a molecule via different reactions other than oxidation. We call it “direct deamination” without oxidation . There are certain reactions which can be non- oxidatively deaminated by specific enzymes and can form NH3. these reactions do not fulfil major role in NH3 formation.

28. Only three types of non oxidative deamnation will be discussed. Amino acid dehydrases Deamination of histidine Amino acid desulfhydrases

29. DIFFERENCE BETWEEN OXIDATIVE AND NONOXIDATIVE DEAMINATION

30. BIOCHEMISTRY 233 T

31. SUMMARY Deamination is the liberation of ammonia via the deamination of an amine group. There are two major types of oxidative and nonoxidative deamination. The nonoxidative deamination includes reactions other than oxidation such as reduction, hydrolysis, and intramolecular reactions. Hence, the key difference between oxidative and nonoxidative deamination is that the oxidative deamination occurs via the oxidation of amino group amino acids whereas the nonoxidative deamination occurs via reactions other than oxidation.

32. DECARBOXYLATION Decarboxylation is the reaction in which the carboxyl group COOH is removed from the amino acid and as a result amine is formed. It is catalyzed by decarboxylases, pyridoxal phosphate-containing enzymes, present in microorganisms and animal tissues. Intestinal bacteria especially, have enzymes which can decarboxylate lysine and ornithine respectively into cadaverine and putrescine, amines which are always present in small quantities in the intestine, but can cause intoxications if their con­centration increases due to abnormal intestinal fermentations.

33. WHAT ARE BIOGENIC AMINES ? Amines are formally derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent. A group of Naturally Occurring, Biologically Active Amines , such as norepinephrine, histamine and serotonin, that act primarily as neurotransmitters and are capable of affecting mental functioning and of regulating blood pressure, body temperature and other bodily processes are called Biogenic Amines. B iogenic amine occurs as a result of the enzymatic reaction catalyzed by pyridoxal phosphate to decarboxylate the amino acid

34. IMPORTANCE OF BIOGENIC AMINES Biogenic amines play an essential role in cell membrane stabilization, immune functions, and prevention of chronic diseases, as they participate in the nucleic acid and protein synthesis. Besides , they are compounds created as the growth regulation neural transmission and inflammation mediators.

35. CLASSIFICATION OF BIOGENIC AMINES Biogenic amines are classified in two categories ; i . On The Basis Of Chemical Structure ii. On The Basis Of Amine Group

36. ON THE BASIS OF CHEMICAL STRUCTURE Aromatic and Heterocyclic Aliphatic di-, tri-, and Polyamines Aliphatic Volatile Amines

37. Aromatic and heterocyclic amines Amino acid precursors Aliphatic precursor Amino acid precursors Aliphatic volatile amines Amino acid precursors Histamine Histadine Putrescine Ornithine Ethanolamine Serine Tryptamine Histadine Cadaverine Lysine Methylamine Tyramine Tyrosine Agmatine Arginine Isopentylamine Serotonin Tryptophan Spermine Ornithine Ethylamine L-Alanine

38. ON THE BASIS OF AMINE GROUP Monoamine Diamine Polyamine Tyramine Histamine Spermine Ethylamine Tryptamine Spermidine Ethanolamine Serotonin Agmatine

39. SOME OF THE IMPORTANT BIOGENIC AMINES Tyramine and its functions ; Tyramine, consisting of tyrosine amino acid as a result of tyrosine decarboxylase activity, is generally found in low amounts. Tyramine leads to several physiological reactions such as blood pressure increase, vasoconstriction, tyramine active noradrenalin secretion, etc., as the sympathetic nervous system controls several functions of the body. Tyramine , stored in the neurons, causes the increase in the tear, salivation and respiratory as well as mydriasis

40. Tryptamine and its functions; Tryptamine consists of tryptophan amino acid as a result of the aromatic L-amino acid decarboxylase activity. Tryptamine is a monoamine alkaloid found in plants, fungi, and animals. Tryptamine, found in trace amounts in mammalian brains, increases blood pressure as well as plays a role as a neurotransmitter or neuromodulator. Histamine and its functions; Histamine, a standard component of the body, consists of histidine amino acid as a result of histidine decarboxylase activity depending on pyridoxal phosphate. Histamine distribution and concentration found in the tissues of all vertebrates are very unsteady . Histamine participates in the essential functions such as neurotransmission and vascular permeability. However , it also plays a role in starting the allergic reactions.

41. Putrescine and its functions; It consists of ornithine amino acid as a result of ornithine decarboxylase activity. Putrescine , produced by bacteria and fungi, contributes to the cell growth and cell division . Spermine and its functions; Whose precursor amino acid is ornithine, is formed from spermidine through the spermine synthase enzyme . Spermine is present in several organisms and tissues, as it is a polyamine that is found in all eukaryotic cells and has a role in the cellular metabolism. It plays a role in the intestinal tissue developments and stabilizes the helical structure in viruses

42. Textbook of Biochemistry-U Satyanarayana Textbook of Biochemistry-DM Vasudevan Text book of medical biochemistry, MN Chatterjee Fundamentals of biochemistry, J.L Jain, Sunjay Jain, Nitin Jain REFERENCES