1. PROTEIN AND AMINO ACID METABOLISM A. A. Osuntoki, Ph.D

2. PROTEINS Protein are polymers of amino acids The monomers are linked by covalent bonds called peptide bonds O II C N II H A peptide bond is formed in a reaction between the carboxylic group of one amino acid and the amino group of another.

3. Proteins are polypeptides There are 20 common amino acids found in naturally occurring proteins The types and arrangement of the amino acid monomers determine the physical and chemical properties of a protein. The arrangement of monomers in a protein chain is under genetic control.

4. BASIC STUCTURE OF AMINO ACIDS

5. CLASSIFICATION OF AMINO ACIDS Various classification modes Nutritional classification : x Essential x Non essential. Chemical classification. x On the basis of the nature of the side chain e.g. aliphatic, aromatic, heterocyclic, carboxylic etc. x On the basis of polarity Metabolic classification x Glucogenic, x Ketogenic x Both glucogenic and ketogenic

6. Amino acids are used for different purposes in our body. Most of the metabolic pool of amino acids is used as building blocks of proteins, Amino acids can not be stored in the body for later use Amino acids not required for immediate biosynthetic needs is deaminated and the carbon skeleton is used as metabolic fuel (10-20 % in normal conditions) or converted into fatty acids via acetyl CoA.

7. PRECURSOR FUNCTION Amino acids in addition to major function as monomers of proteins are essential precursors of a variety of important biomolecles such as Nucleotides Nucleotide coenzymes Haem Various hormones e.g epinephrine and norepinephrine neurotransmitters Glutathione

8. AMINO ACID CATABOLISM The main products of the catabolism of the carbon skeleton of the amino acids are pyruvate, oxalacetate, α-ketoglutarate, succinyl CoA, fumarate, acetyl CoA and acetoacetyl CoA. When carbohydrates are not available (starvation, fasting) -or cannot be used properly, as in diabetes mellitus, amino acids can become a primary source of energy and an important source of glucose for those tissues that only can use this sugar as metabolic fuel. The formation of glucose from amino acids (gluconeogenesis) in liver and kidney is intensified during starvation and this process becomes the most important source of glucose for the brain, RBC and other tissues.

9. AMINO ACID DEAMINATION The first reaction in the breakdown of an amino acid Involves the removal of α- amino group The excess nitrogen is excreted through the urea cycle The carbon skeleton is used for energy generation or glucose production

10. Most amino acids are deaminated by transamination Transamination does not result in any net deamination Deamination occurs largely through the oxidative deamination of glutamate by glutamate dehydrogenase GDH

11. DEAMINATION

13. KETOGENIC AND GLUCOGENIC AMINO ACIDS Amino acids can be classified according to the metabolic fate of the carbon skeleton in: ketogenic and glucogenic Ketogenics: Amino acids that yield acetyl CoA or acetoacetyl CoA ( e.g. they do not produce metabolites that can be converted in glucose). Lysine and Leucine are the only amino acids that are exclusively ketogenic. Glucogenic: Amino acids whose catabolism yields to the formation of Pyruvate or Krebs Cycle metabolites, that can be converted to glucose through gluconeogenesis. Glucogenic amino acids are: Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glycine, Histidine, Methionine, Proline, Serine, and Valine. Glucogenic and ketogenic: Amino acids that yield some products that can become glucose and others that yields acetyl CoA or Acetoacetyl CoA. Isoleucine, Phenylalanine, Tryptophan, Tyrosine and Threonine.

14. INBORN ERRORS OF AMINO ACID METABOLISM Several inborn errors Most are recessive Examples: Phenylketonuria Alcaptonuria Albinism

15. UREA CYCLE The excess nitrogen produced from the metabolic breakdown of amino acids is excreted via the urea cycle Urea is synthesized in the liver by urea cycle enzymes Secreted into the bloodstream Sequestered by the kidneys for excretion in the urine

17. THANK YOU