Amino acid metabolism.

Slides:



Advertisements
Similar presentations
Lecture 12 Modified from internet resources, journals and boks
Advertisements

Chapter 5 - Cell Respiration and Metabolism Metabolism - the sum of all the chemical reactions that occur in the body. It is comprised of:  anabolism.
How Cells Harvest Energy Chapter 7. 2 Respiration Organisms can be classified based on how they obtain energy: autotrophs: are able to produce their own.
Detoxification of ammonia and biosynthesis of urea. The basic features of nitrogen metabolism were elucidated initially in pigeons.
Amino acid oxidation and the production of urea
The Urea Cycle بسم الله الرحمن الرحيم Dr. Mahmoud Sirdah Dr. Mahmoud Sirdah.
Welcome to class of Metabolism of nitrogen compound Dr. Meera Kaur.
Degradation of amino acids Amino acid breakdown can yield: –Acetyl-CoA –  -KG –Succinyl-CoA –OAA –fumarate.
Protein metabolism Protein digestion: A)In stomach: passage of food into stomach stimulates gastric mucosa to secret a polypeptide hormone called: Gastrin.
Amino Acids Metabolism: Disposal of Nitrogen.
By Amr S. Moustafa, MD, PhD Medical Biochemistry Unit, Path. Dept. College of Medicine, King Saud University Urea Cycle.
BIOC/DENT/PHCY 230 LECTURE 4. Nitrogen Metabolism Many nitrogen containing compounds eg. Amino acids, nucleotides, porphyrins, neurotransmitters There.
Catabolism of proteins and amino acids. Reactions in the attachment of ubiquitin to proteins.
METABOIC FATE OF AMINO ACIDS. Intracellular proteases hydrolyze internal peptide bonds, of protein releasing peptides, which are then degraded to free.
Digestion of Proteins 25.7 Degradation of Amino Acids 25.8 Urea Cycle Chapter 25 Metabolic Pathways for Lipids and Amino Acids.
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Chapter 18 Metabolic.
BIOC 460 DR. TISCHLER LECTURE 38 AMINO ACID DEGRADATION/ UREA CYCLE.
Metabolism II.
Digestion of Protein The goal of protein digestion is the hydrolysis of all peptide bonds to produce free amino acids. No chemical digestion of protein.
Metabolism of amino acids, purine and pyrimidine bases
LIPID METABOLISM – BLOOD LIPIDS
DR AMINA TARIQ BIOCHEMISTRY
Metabolism of Amino Acid
General pathways of amino acids transformation.
Amino acid metabolism · Nitrogen balance protein catabolism, synthesis biosynthesis normal N balance: N ingested = N excreted negative N balance: N ingested.
# 2 Degradation of Amino Acids
Amino acid degradation Most of absorbed dietary amino acids are catabolized by 2 subsequent steps: I- Removal of α-amino group: α-amino group is removed.
Amino Acid Metabolism. Intestinalsynthesize apoproteins (for lipoproteins) Epithelia:synthesize digestive enzymes glutamine degradation is a primary source.
Chapter 5 Cell Respiration and Metabolism. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metabolism All.
Fig. 23-1, p.630 Amino acids act principally as the building blocks and to the synthesis of variety of other biologically molecules. When a.acids deaminated.
How Cells Harvest Energy
Dr. Saidunnisa Professor of Biochemistry
Nitrogen Cycle. Summary of Protein and Amino Acid Metabolism.
Amino acid metabolism M.F.Ullah,Ph.D COURSE TITLE: BIOCHEMISTRY 2
By Dr Rana Hasanato Medical Biochemistry Unit, Path. Dept. College of Medicine, King Saud University Urea Cycle.
AMINO ACIDS METABOLISM Course: MEDICIMAL CHEMISTRY 1 Course Code: 301.
Metabolism of Amino Acid
The Nitrogen Cycle Nitrite reductase Nitrate reductase nitrogenase.
Amino acids - Classifications, Amino acids Physico – Chemical Properties, Protein structure, folding & function, Nitrogen Cycle Nitrogen Balance, Reductive.
Special aspects of renal metabolism Mahmoud A. Alfaqih BDS PhD Jordan University of Science and Technology.
Chapter Twenty-Three The Metabolism of Nitrogen. Nitrogen Fixation Nitrogen fixation is the reduction of N 2 to NH 3: Bacteria are responsible for the.
Amino Acid Metabolism CHY2026: General Biochemistry.
Enter in the formation of A.A. pool
Dr. Ghufran Mohammed Hussein
Urea Biosynthesis Transamination. 2. Oxidative Deamination.
Learning Objectives 1. What Processes Constitute Nitrogen Met.? 2. How Is Nitrogen Incorporated into Biologically Useful Compounds? 3. What Role Does Feedback.
24.6 Degradation of Proteins and Amino Acids
Catabolism of amino acids
Oxidative Decarboxylation and Krebs Cycle
Human Cells Cellular Respiration
Chapter 7: Metabolism The Basics Glycolysis TCA Fat Metabolism
Amino acid metabolism Metabolism of amino acids differs, but 3 common reactions: Transamination Deamination Decarboxylation.
Cellular Respiration Chapter 8.
Amino Acids Metabolism:
Amino Acid Metabolism.
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.
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.
MBG304 Biochemistry Lecture 9: Amino acid metabolism
Urea Cycle Clinical Biochemistry Unit, Path. Dept.
UNIT 12 CS BASIC CONCEPTS OF METABOLISM
Cell Physiology: Metabolism
Amino Acid Metabolism The continuous degradation and synthesis of cellular proteins occur in all forms of life. Each day humans turn over 1–2% of.
Metabolism II.
REVIEW SLIDES.
Nitrogen metabolism Part C:
Determination of the enzyme ALT (SGPT) & AST activity in serum by enzymatic method using Biophotometer.
How Cells Harvest Energy
Biochemistry UREA CYCLE
Dr. Sumbul Fatma Medical Biochemistry Unit Department of Pathology
PROTEIN METABOLISM Prof.Dr.Fügen Aktan
Presentation transcript:

Amino acid metabolism

Content Introduction General Metabolism of amino acids Transamination Deamination

Introduction Amino acid catabolism is part of the whole body catabolism Nitrogen enters the body in a variety of compounds present in the food, the most important being amino acids present in the dietary protein. Nitrogen leaves the body as urea, ammonia, and other products derived from amino acid metabolism

Fate of amino acids Body protein Synthesis of tissue protein Synthesis of Biological compounds Synthesis of glucose, ketone bodies or fatty acids Oxidation in TCA cycle to yield energy and CO2 Dietary protein Synthesis of non essential amino acids Amino acid Pool

General Metabolism of amino acids Anabolic reactions where proteins are synthesized Catabolic reactions where dietary proteins & body proteins are broken down to amino acids Synthesis of specialized products such as heme, creatine, purines and pyrimidines

4)Transamination: amino group is removed to produce carbon skeleton(keto acid),the amino group is excreted as urea 5) Carbon skeleton is used for the synthesis of non essential amino acids 6) Carbon skeleton is also used for gluconeogenesis or for complete oxidation 7) Amino acids are used for, other minor metabolic functions like conjugation,methylation, amidation etc..

Biosynthesis of urea Urea biosynthesis occurs in stages: Transdeamination (Removal of α-amino group) by –a coupled process of transamination and deamination Transamination forms Glutamate in peripheral cells Deamination of glutamate forms ammonia in liver (2) Minor pathway of oxidative and non oxidative deamination produce ammonia in peripheral cells (3)Ammonia transport-Ammonia is transported to liver as glutamate, glutamine or alanine (4) Detoxification of released ammonia – Ammonia is detoxified by specific reactions (Urea cycle) forming urea in liver

Transamination Transamination interconverts pairs of α-amino acids and α -keto acids. During Transamination, the amino group of an amino acid (amino acid R 1) is transferred to a keto acid (keto acid R 2), this produces a new keto acid while from the original keto acid, a new amino acid is formed

Aminoacid + Keto acid New Keto acid + New Amino acid

Role of B6 Phosphate (PLP) in transamination The transfer of α-amino group from donor amino acid to Pyridoxal phosphate forms Pyridoxamine phosphate, and a keto acid. The α-amino group is finally passed on to acceptor α-keto acid to form a new amino acid.

Eg: (1) ALT- Serum glutamate Alanine transferase Reaction catalyzed can be represented as follows-

Eg: (2) AST-Serum glutamate-oxaloacetate-aminotransferase (SGOT) Reaction catalyzed can be represented as follows-

Characteristics of Transamination The general process of transamination is reversible ,occurs in all the tissues It is catalyzed by Transaminases, also called amino transferases that require PLP(derived from Vit B6) as coenzyme Specific transaminases exist for each pair of amino &keto acids.however only two make significant contribution for transamination ,aspartate transaminase (AST/SGOT) and alanine transaminase(ALT/SGPT) Synthesis of non essential amino acids: all non essential aa can be synthesized by body from keto acids available from other sources. Eg: pyruvate to alanine, oxaloacetate to aspartate.. Glycine,alanine,serine,cysteine,asparagine,glutamine,aspartic acid,glutamic acid, asparagine,glutamine,tyrosine,proline- non essential amino acids

5) Interconversion of aa ,so that equalization of quantity of non essential aa can be achieved 6) It diverts excess aa towards energy generation 7) The resultant α-Keto acid can be completely oxidized to provide energy, glucose, fats or ketone bodies depending upon the cellular requirement. 8) Amino acid undergo transamination to finally concentrate nitrogen in glutamate ,which is the only aa that undergoes oxidative deamination to a significant extent to liberate free NH3 for urea synthesis

9) All aa except lysine,threonine, proline & hydroxyproline participate in transamination 10) Transamination is not restricted to α -amino groups.The δ -amino group of ornithine readily undergoes transamination. 11) Serum transaminases are important for diagnostic and prognostic purpose

Clinical significance of Transaminases Serum aminotransferases such as serum glutamate-oxaloacetate-aminotransferase (SGOT) (also called Aspartate aminotransferase, AST) and serum glutamate-pyruvate aminotransferase (SGPT) (also called alanine transaminase, ALT) have been used as clinical markers of tissue damage, with increasing serum levels indicating an increased extent of damage. 

AST-Serum glutamate-oxaloacetate-aminotransferase (SGOT) AST is found in the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes, and erythrocytes The enzyme is both cytoplasmic as well as mitochondrial in nature Normal levels 8-20 U/L

AST… Elevated in Myocardial Infarction Significantly elevated in liver disease, primary hepatoma In alcoholic hepatitis: AST> ALT ↑ AST can also be seen in Muscle disorders like muscular dystrophies

ALT ALT is found primarily in the liver. The normal serum activity ranges between Levels: 13-35 U/L in males,10-30 U/L in females

ALT.. Very high levels in acute hepatitis of toxic /viral origin( 300-1000 U/L) ALT elevation> AST elevation Moderate increase in cirrhosis,hepatitis C ,NASH( 50-100 U/L)

"Education is the best friend "Education is the best friend. An educated person is respected everywhere. Education beats the beauty and the youth." Chanakya quotes  (Indian politician, strategist and writer, 350 BC-275BC)

Deamination Removal of amino group from the amino acid as NH3 is termed as deamination

Histidase

Oxidative deamination Libration of free ammonia from the amino group of amino acids coupled with oxidation. Takes place mainly in liver & kidney Purpose: 1) To provide ammonia for urea synthesis. 2) To provide alpha keto acid for energy generation

This reaction is inhibited by ATP/GTP and stimulated by ADP/GDP thus when energy level is low more AA degraded to form alpha KG. In addition to equilibrating amino groups among available a-keto acids, transaminases funnel amino groups from excess dietary amino acids to those amino acids (e.g., glutamate) that can be deaminated Only a few amino acids can be deaminated directly. Glutamate Dehydrogenase catalyzes a major reaction that effects net removal of N from the amino acid pool .  Glutamate Dehydrogenase is one of the few enzymes that can utilize either NAD+ or NADP+ as electron acceptor (Enzyme)

The nitrogen atom that is transferred to α-ketoglutarate in the transamination reaction forming Glutamate, is converted into free ammonium ion by oxidative deamination Glutamate occupies a central place in the amino acid metabolism Basically it acts as a collector of amino group of the amino acids.

This reaction is catalyzed by glutamate dehydrogenase(GDH) This enzyme is unusual in being able to utilize either NAD+ or NADP+ Glutamate dehydrogenase is Zinc containing complex enzyme (six identical subunits), located in mitochondria, as are some of the other enzymes required for the production of urea.

Regulation of Glutamate dehydrogenase(GDH) The activity of GDH is allosterically regulated Guanosine triphosphate (GTP) and adenosine triphosphate (ATP) are allosteric inhibitors, whereas Guanosine diphosphate (GDP) and adenosine diphosphate (ADP) are allosteric activators Hence, a lowering of the energy charge (more of ADP and GDP) accelerates the oxidation of amino acids favoring formation of alpha keto glutarate that can be channeled towards TCA cycle for complete oxidation to provide energy Steroid & thyroid hormones inhibit GDH

Thus Transamination and deamination are coupled processes though they occur at distant places Often termed as "transdeamination."

At right is summarized the role of transaminases in funneling amino N to glutamate, which is deaminated via Glutamate Dehydrogenase, producing NH4+.

Minor pathways of oxidative deamination Via, L-amino acid oxidase 2) D-amino acid oxidase

L-amino acid oxidase: acts on all amino acids except hydroxy amino acids & dicarboxylic amino acids Uses FMN as co-enzyme

+ Release of ammonia

D-amino acid oxidase: Acts on glycine & D amino acid that may be formed by bacterial metabolism Uses FAD as co-enzyme

Minor pathways of Non oxidative deamination Some of the amino acids can be deaminated to liberate NH3 without undergoing oxidation Types of reactions: Dehydratases: requires PLP as coenzyme Desulfhydrases: requires PLP as coenzyme Histidase