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AMINO ACID METABOLISM PowerPoint Presentation

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Description : Check out this medical presentation on Alanine Aminotransferase (alanine transaminase), which is titled "AMINO ACID METABOLISM", to know about the metabolic relationship of amino acids and transamination reaction.

Tags : Alanine Aminotransferase, alanine transaminase, AMINO ACID METABOLISM, amino acids, transamination reaction

Published on : Jul 05, 2021 | Views : 4830 | Downloads : 15

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Slide 1-

AMINO ACID METABOLISM Jana Novotná Department of the Medical Chemistry and Biochemistry The 2nd Faculty of Medicine, Charles Univ.
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Amino acid structure
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The 20 common amino acids of proteins
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Metabolic relationship of amino acids
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Endopeptidases – hydrolyse the peptide bond inside a chain: pepsin, trypsin, chymotrypsin Exopeptidases – split the peptide bond at the end of a protein molecule: aminopeptidase, carboxypeptidases Dipeptidases Enzymes cleaving the peptide bond pepsin (pH 1.5 – 2.5) – peptide bond derived from Tyr, Phe, bonds between Leu and Glu trypsin (pH 7.5 – 8.5) – bonds between Lys a Arg chymotrypsin (pH 7.5 – 8.5) – bonds between Phe a Tyr
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Essential amino acids in humans Arginine* Histidine* Isoleucine Leucine Valine Lysine Methionine Threonine Phenylalanine Tryptophan *Required to some degree in young growing period and/or sometimes during illness.
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Non-essential and nonessential amino acids in humans Alanine Asparagine Aspartate Glutamate Glutamine Glycine Proline Serine Cysteine (from Met*) Tyrosine (from Phe*) * Essential amino acids Can be formed from a-keto acids by transamination and subsequent reactions.
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General reactions of amino acid catabolism
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The fate of the amino group during amino acid catabolism
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Transamination reaction The first step in the catabolism of most amino acids is removal of a-amino groups by enzymes transaminases or aminotransferases All aminotransferases have the same prostethic group and the same reaction mechanism. The prostethic group is pyridoxal phosphate (PPL), the coenzyme form of pyridoxine (vitamin B6)
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Biosynthesis of amino acid: transamination reactions amino acid1 +a-keto acid2 amino acid2 +a-keto acid1 Glutamate + a-Ketoglutarate + Pyridoxal phosphate (PLP)- dependent aminotransferase Keto-acid Amino acid
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Active metabolic form of vitamin B6
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Mechanism of transamination reaction: PPL complex with enzyme accept an amino group to form pyridoxamine phosphate, which can donate its amio group to an a-keto acid.
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All amino acids except threonine, lysine, and proline can be transaminated Transaminases are differ in their specificity for L-amino acids. The enzymes are named for the amino group donor.
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Clinicaly important transaminases ALT Alanine-a-ketoglutarate transferase ALT (also called glutamate-pyruvate transaminase – GPT) Aspartate-a-ketoglutarate transferase AST (also called glutamate-oxalacetate transferase – GOT) Important in the diagnosis of heart and liver damage caused by heart attack, drug toxicity, or infection.
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Glucose-alanine cycle Ala is the carrier of ammonia and of the carbon skeleton of pyruvate from muscle to liver. The ammonia is excreted and the pyruvate is used to produce glucose, which is returned to the muscle. Alanine plays a special role in transporting amino groups to liver. According to D. L. Nelson, M. M. Cox :LEHNINGER. PRINCIPLES OF BIOCHEMISTRY Fifth edition
Slide 17-

Glutamate releases its amino group as ammonia in the liver The amino groups from many of the a-amino acids are collected in the liver in the form of the amino group of L-glutamate molecules. Glutamate undergoes oxidative deamination catalyzed by L-glutamate dehydrogenase. Enzyme is present in mitochondrial matrix. It is the only enzyme that can use either NAD+ or NADP+ as the acceptor of reducing equivalents. Combine action of an aminotransferase and glutamate dehydrogenase referred to as transdeamination.
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Ammonia transport in the form of glutamine Glutamine synthetase Excess ammonia is added to glutamate to form glutamine. Glutamine enters the liver and NH4+ is liberated in mitochondria by the enzyme glutaminase. Ammonia is remove by urea synthesis.
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Relationship between glutamate, glutamine and a-ketoglutarate a-ketoglutarate glutamate glutamine NH3 NH3 NH3 NH3 E E E glutamate + NAD+ + H2O a-ketoglutarate NH3 + + NADH E glutamate NH3 + glutamine ATP E ADP glutamine H2O + glutamate NH3 + E A. Glutamate dehydrogenase B. Glutamine synthetase (liver) C. Glutaminase (kidney) From transamination reactions To urea cycle
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Oxidative deamination L-amino acid oxidase produces ammonia and a-keto acid directly, using FMN as cofactor. The reduced form of flavin must be regenerated by O2 molecule. This reaction produces H2O2 molecule which is decompensated by catalase. Is possible only for hydroxy amino acids
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Amino acid metabolism and central metabolic pathways 20 amino acids are converted to 7 products: pyruvate acetyl-CoA acetoacetate a-ketoglutarate succynyl-CoA oxalacetate fumarate
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Glucogenic Amino Acids formed: a-ketoglutarate, pyruvate, oxaloacetate, fumarate, or succinyl-CoA Aspartate Asparagine Arginine Phenylalanine Tyrosine Isoleucine Methionine Valine Glutamine Glutamate Proline Histidine Alanine Serine Cysteine Glycine Threonine Tryptophan
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Ketogenic Amino Acids formed acetyl CoA or acetoacetate Lysine Leucine
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Both glucogenic and ketogenic amino acids formed: a-ketoglutarate, pyruvate, oxaloacetate, fumarate, or succinyl-CoA in addition to acetyl CoA or acetoacetate Isoleucine Threonine Tryptophan Phenylalanine Tyrosine
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Alanine Serine Cysteine Threonine The C3 family: alanine, serine, cysteine and threonine are converted to pyruvate Pyruvate
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The C4 family: aspartate and asparagine are converted into oxalacetate Aspartic acid Asparagine Oxalacetate
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The C5 family: several amino acids are converted into a-ketoglutarate through glutamate Glutamine Proline Histidine Arginine a-ketoglutarate
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Interconversion of amino acids and intermediates of carbohydrate metabolism and Krebs cycle
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Metabolism of some selected amino acids
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Serine biosynthesis from glycolytic intermediate 3-phosphoglycerate Copy from: http://themedicalbiochemistrypage.org/amino-acid-metabolism.html
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Glycine biosynthesis from serine Reaction involves the transfer of the hydroxymethyl group from serine to the cofactor tetrahydrofolate (THF), producing glycine and N5,N10-methylene-THF. Copy from: http://themedicalbiochemistrypage.org/amino-acid-metabolism.html
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Glycine oxidation to CO2 Glycine produced from serine or from the diet can also be oxidized by glycine decarboxylase (also referred to as the glycine cleavage complex, GCC) to yield a second equivalent of N5,N10-methylene-tetrahydrofolate as well as ammonia and CO2. Copy from: http://themedicalbiochemistrypage.org/amino-acid-metabolism.html
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The sulfur for cysteine synthesis comes from the essential amino acid methionine. SAM serves as a precurosor for numerous methyl transfer reactions (e.g. the conversion of norepinephrine to epinenephrine). Cysteine and methionine are metabolically related Condensation of ATP and methionine yield S-adenosylmethionine (SAM) SAM
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Cysteine synthesis Copy from: http://themedicalbiochemistrypage.org/amino-acid-metabolism.html Conversion of SAM to homocysteine. Condensation of homocysteine with serine to cystathione. Cystathione is cleavaged to cysteine. Conversion of homocysteine back to Met. N5-methyl-THF is donor of methyl group. * *folate + vit B12
Slide 35-

Genetic defects for both the synthase and the lyase. Missing or impaired cystathionine synthase leads to homocystinuria. High concentration of homocysteine and methionine in the urine. Homocysteine is highly reactive molecule. Disease is often associated with mental retardation, multisystemic disorder of connective tissue, muscle, CNS, and cardiovascular system. Homocystinuria
Slide 36-

Biosynthesis of Tyrosine from Phenylalanine Phenylalanine hydroxylase is a mixed-function oxygenase: one atom of oxygen is incorporated into water and the other into the hydroxyl of tyrosine. The reductant is the tetrahydrofolate-related cofactor tetrahydrobiopterin, which is maintained in the reduced state by the NADH-dependent enzyme dihydropteridine reductase
Slide 37-

Hyperphenylalaninemia - complete deficiency of phenylalanine hydroxylase (plasma level of Phe raises from normal 0.5 to 2 mg/dL to more than 20 mg/dL). The mental retardation is caused by the accumulation of phenylalanine, which becomes a major donor of amino groups in aminotransferase activity and depletes neural tissue of α-ketoglutarate. Absence of α-ketoglutarate in the brain shuts down the TCA cycle and the associated production of aerobic energy, which is essential to normal brain development. Newborns are routinelly tested for blood concentration of Phe. The diet with low-phenylalanine diet. Phenylketonuria
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valine isoleucine leucine a-ketoglutarate glutamate (transamination) a-ketoisovalerate a-keto-b-methylbutyrate a-ketoisokaproate oxidative decarboxylation Dehydrogenase of a-keto acids* CO2 NAD+ NADH + H+ isobutyryl CoA a-methylbutyryl CoA isovaleryl CoA Dehydrogenation etc., similar to fatty acid b-oxidation propionyl CoA acetyl CoA acetoacetate acetyl CoA propionyl CoA + + Catabolism of branched amino acids
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Branched-chain aminoaciduria Disease also called Maple Syrup Urine Disease (MSUD) (because of the characteristic odor of the urine in affected individuals). Deficiency in an enzyme, branched-chain α-keto acid dehydrogenase leads to an accumulation of three branched-chain amino acids and their corresponding branched-chain α-keto acids which are excreted in the urine. There is only one dehydrogenase enzyme for all three amino acids. Mental retardation in these cases is extensive.
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Histidine Metabolism: Histamine Formation Histidine Histamine Histidine decarboxylase CO2 Histamine: Synthesized in and released by mast cells Mediator of allergic response: vasodilation, bronchoconstriction
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Tryptophan catabolism Tryptophan has complex catabolic pathway: the indol ring is ketogenic the side chain forms the glucogenic products Kynurenate and xanthurenate are excrete in the urine.
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Enzymes which metabolised amino acides containe vitamines as cofactors THIAMINE B1 (thiamine diphosphate) oxidative decarboxylation of a-ketoacids RIBOFLAVIN B2 (flavin mononucleotide FMN, flavin adenine dinucleotide FAD) oxidses of a-aminoacids NIACIN B3 – nicotinic acid (nikotinamide adenine dinucleotide NAD+ nikotinamide adenine dinukleotide phosphate NADP+) dehydrogenases, reductase PYRIDOXIN B6 (pyridoxalphosphate) transamination reaction and decarboxylation FOLIC ACID (tetrahydropholate) Meny enzymes of amino acid metabolism
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http://themedicalbiochemistrypage.org/amino-acid-metabolism.html Helpful website