A m I n o A c I d S M E T A B O L I S M
A m I n o A c I d S M E T A B O L I S M
Objectives:
1.To study Amino Acid Metabolism 2. Overall Nitrogen Metabolism. 3.Digestion & Absorption of Dietary Protein. 4. Removal of Nitrogen from Amino Acids. 5.Urea cycle and Its disorders. 6. Metabolism of Ammonia. 7. Fate & Metabolism of individual Amino Acids.
A m I n o A c I d S M E T A B O L I S M
Introduction
Unlike fat and carbohydrate, Amino Acids are not stored in the body, Protein that exist is to maintain the supply of AA for future use.
AA. Must be supplied from the diet (Exogenous)ORFrom the catabolism of normal proteins inside body tissues……….(Endogenous).What about the Excess?
A m I n o A c I d S M E T A B O L I S M
The excess enter 2 phases:Phase1……… Removal of α Amino Acids Transamination&Oxidative deamination
Ammonia & α Ketoacids (Carb. Skeleton) Portion of ammonia is excreted in the urine but most of it will be converted to the less toxic compound “Urea”.
A m I n o A c I d S M E T A B O L I S M
Phase2…………… α Ketoacids Common intermediate of energy producing metabolic pathways
A m I n o A c I d S M E T A B O L I S M
Amino Acid Pool
AA.s are present in the body cells, blood, ECF. They are essential constituents of protoplasm. They are incorporated into cellular structure of protein, collagen, myosin, Hemoglobin & transferrin.
3 sources of AA: AA provided by degradation of protein(Endogenous) AA provided by dietary protein (Exogenous). 3. Synthesis of non essential AA.
A m I n o A c I d S M E T A B O L I S M
A m I n o A c I d S M E T A B O L I S M
R= alkyl or heterocyclic group
General formula
A m I n o A c I d S M E T A B O L I S M
Peptide bond
Peptide bond : 2 or more AA Poly peptide > 10 AA
A m I n o A c I d S M E T A B O L I S M
Formation of Peptide bond: The bond formed between two amino acid is called peptide bond. When 2 A.A. are joined together di-peptide will be formed , if 3 A.A. are joined together tri-peptide will form. If 2-10 A.A. are joined together oligo-peptide is formed . If it is more than 10 it is called poly-peptide. Polypeptides are large peptide chains containing large no. of peptide bond less than 100 A.A. residue. If the A.A. residue is more than 100 A.A. it is called protein.
A m I n o A c I d S M E T A B O L I S M
A-non migrating neutral( mono amino – mono carboxylic ) * aliphatic straight chain and branched chain glycine , alanine ,valine * aromatic phenyl alanine tyrosine tryptophan * sulfur containing AA cysteine cystine methionine B-basic AA lysine arginine histidine
C-Acidic AA Aspartic A. Glutamic A.
Imino Group(Heterocyclic AA) Proline Hydroxyproline
Classification: 3 groups
A m I n o A c I d S M E T A B O L I S M
Nonessential
Essential
Alanine
Arginine*
Asparagine
Histidine *
Aspartate
Valine
Cysteine
Lysine
Glutamate
Isoleucine
Glutamine
Leucine
Glycine
Phenylalanine
Proline
Methionine
Serine
Threonine
Tyrosine
Tyrptophan
*The amino acids Arg, His are considered “conditionally essential”
A m I n o A c I d S M E T A B O L I S M
Digestion Of Dietary Protein
Proteins are generally too large to be absorbed by the intestine, they must be hydrolysed to give their constituent AA which can be absorbed.
Stomach
Stomach: the gastric juice and the HCL pH(2-3) too dilute to hydrolysed, In the serous cells pepsinogen is activated to pepsin or auto catalytically by other pepsin molecules that have already activated. Pepsin releases peptides and few AA.
Pancreas: large polypeptides produced in the stomach are further hydrolysed or cleaved into oligopeptide and AA by the action of pancreatic proteases. These enzymes are activated by 2 hormones; cholecystokinin and secretin. The Trypsinogen is activated into trypsin which is one of five major classes that also contain chymotrypsin, elastase, carboxypeptidase A & B..
Pancreas
Intestine
A m I n o A c I d S M E T A B O L I S M
Intestine : In the intestine lumianl surface contains aminopeptidases that repeatedly cleaves the oligopeptides to produce free AA and small peptides.
A m I n o A c I d S M E T A B O L I S M
Absorption
Free AA are taken into the intestinal cells by Na-linked secondary transport system. Di-and tri peptides are taken up by H+- linked transport system. The peptides are hydrolyzed in the cytosol to AA before being released in to the portal system .
Thus, only free AA are found in the portal vein after meals containing proteins . These AAs are either metabolized by the liver or released into the general circulation. Branched-chain AAs are important examples of AAs that are not metabolized by the liver and sent from the liver into the systemic blood circulation.
A m I n o A c I d S M E T A B O L I S M
Specificity;tryp cleaves the carbonyl gp of pptide contributed by ar.,ly
A m I n o A c I d S M E T A B O L I S M
Glucogenic &Ketogenic Amino Acids
Glucogenic AA: whose catabolism produces pyruvate or one of the intermediates of the citric acid cycle.These intermediates are substrate for gluconeogenesis,which can give rise to glucose or glycogen in the live or the muscles.
Ketogenic AA: whose catabolism produces acetoacetate or one of its precursors like acetyl coA or acetoacetyl coA. Acetoacetate is one of the ketone bodies which also include B-hydroxybutyric acid and acetone. *only leucine and lysine are purely ketogenic .
Next Fig
A m I n o A c I d S M E T A B O L I S M
Glucogenic &Ketogenic Amino Acid
A m I n o A c I d S M E T A B O L I S M
The catabolism of the AAs found in proteins pass through different steps:Removal of α AA.2. Breakdown of the resulting carbon skeleton.These pathways form seven intermediate products. oxaloacetate α ketoglutarate Pyruvate Fumarate Succinyl CoA Acetyl CoA Acetoacetate