Amino Acid Metabolism.pdf

Amino Acid Metabolism Protein Metabolism • Proteins are not stored in the body for future use • Excess and unwanted proteins are degraded to amino acids • Constant turn-over of body proteins – Each day, ~ 1-2% of body proteins are degraded and new ones are formed Protein Turnover Synthesis of n...

Amino Acid Metabolism Protein Metabolism • Proteins are not stored in the body for future use • Excess and unwanted proteins are degraded to amino acids • Constant turn-over of body proteins – Each day, ~ 1-2% of body proteins are degraded and new ones are formed Protein Turnover Synthesis of nonEssential amino acids Dietary Protein Body Amino Acid Pool (~100 g) I Synthesis of body protein of Glucose/ glycogen Degradation CO2, H2O Synthesis of other N-containing Products Nucleotides, neurotransmitters Ketone bodies Fatty acids Amino Acid Metabolism O • 1st step in catabolism is the removal of the NH2 group. • Remaining carbon skeleton can be broken down in a number of ways • Nitrogen removed is either used for the synthesis of other N-containing compounds or excreted as urea. • Nitrogen is removed in two major ways: – transamination – deamination. I TRANSAMINATION • Transfer of NH2 to from AA to -ketoglutarate, which becomes glutamate • The amino acid becomes a keto acid • Glutamate is the major NH2-group donor for the synthesis of non-essential amino acids • Catalyzed by Aminotransfereases • need vitamin B6 in the form of pyridoxal phosphate (PLP). • All amino acids with the exception of lysine and threonine participate in transamination Lysine threonine Transamination • Major Transaminases are: – Alanine aminotransferase (ALT) – Aspartate aminotransferase (AST) anime A Z aspartate Is A r To Ast g DEAMINATION (OXIDATIVE DEAMINATION) • NH2 from majority of the amino acids is transferred to -ketoglutarate which becomes glutamate • The NH2 from glutamate is removed by the oxidative deamination. • The reaction is catalyzed by glutamate dehydrogenase N • NH2-group is released as NH3 • The ammonia released is toxic and has to detoxified i T • Regulation of glutamate dehydrogenase: – is an allosteric enzyme; activated by ADP/GDP; inhibited by ATP/GTP. As GDP Oxidative deamination Glutamate dehydrogenase T t on her EID It of Moffat THE UREA CYCLE • Ammonia is produced in the liver and tissues • From tissues it travels to the liver in either of the two forms: – As glutamine: glutamate + NH3 → glutamine, which release the NH3 in the liver. – As Alanine: pyruvate + NH3 → Alanine. – Alanine transfers its NH2 to -ketoglutarate in the liver – by oxidative deamination glutamate releases NH3. The Urea Cycle • • • • • cytosol mtor Ammonia is converted into urea by the urea cycle in the liver. The precursors are NH3, CO2 and ATP (all are generated in the mitochondria) The first two reaction of the cycle take place in the mitochondria. The remaining are in the cytosol E In the first reaction, CO2, NH3 and ATP form carbamoyl phosphate Catalyzed by the carbamoyl phohphate synthetase-I The Urea Cycle • Carbamoyl phosphate combines with ornithine and forms citrulline • Citrulline gets out of mitochondria into the cytosol, where the cycles completes forming urea and regenerating ornithine • Ornithine reenters the mitochondria • The overall reaction is: • NH00 3 + CO2 + 3ATP 0 + aspartate → urea + fumarate + 2ADP + AMP + 2Pi + PPi + 3H2O Q Regulation of Urea cycle • Regulation of the cycle is at the first reaction • Carbamoyl phosphate synthetase-I is the ratelimiting enzyme and is activated by N-acetyl glutamate DEGRADATION OF THE CARBON SKELETON OF THE AMINO ACIDS • The carbon skeleton of the amino acids can be converted into one of the following intermediates: – – – – – – – Oxaloacetate -ketoglutarate pyruvate s fumarate I succinyl coA A acetyl coA 1 Acetoacetater oxaloacetate L ketoglutarate pymae sural CoA acetyl Con fur are Acetum • Amino acids are classified as either glucogenic or ketogenic. or gu or Glucogenic and ketogenic AA Tea • Glucogenic: me – Converted into pyruvate or any intermediate of the TCA cycle – These can be converted into glucose, hence called glucogenic • Ketogenic: – Converted into acetoacetate or acetyl CoA. – These cannot be converted into glucose but can be converted into fatty acids or ketone bodies, hence called ketogenic. • Leucine and lysine are only ketogenic • Tyrosine, isoleucine, phenylalanine and tryptophan are both ketogenic as well as glucogenic • All other are glucogenic I IEEE were mere methionine one The we EEE METABOLIC DEFECTS IN AMINO ACID METABOLISM • Also called inborn errors of metabolism • Caused by mutations in the genes of the enzymes involved • Results in either total loss of enzyme function or its reduced activity Mass • Most of these result in mental retardation and other developmental disabilities • More than 50 defects are reported • Some are more common than others • Important ones are PKU, maple syrup urine disease, albinism, homocystinuria and alkaptonuria ago • Neonatal screening is required in some places for these genetic disease.