Biochemistry Midterms

• Amino group


  Will be removed and is converted to ammonia, released as urea to be excreted in the urine
• Carbon skeleton


  Can be recycled to form new proteins or it can also participate in the catabolism of new compounds. It can also enter other metabolic pathways to form glucose, ketone bodies, and acetyl CoA
• Metabolism of amino acids interfaces with carbohydrates and lipid metabolism

  
• It was discovered through radioisotope labeling and traced where the carbon skeleton will proceed to what pathway. Some of the amino acids are then found out to be ketogenic, glucogenic, or both

  
• Virtually all carbon skeletons can be converted to intermediates of the Glycolytic pathway, Citric acid cycle, and Lipid metabolism

  
• Every amino acid follows different reactions but the general rule would be after the elimination of the amino group
• Citric acid cycle


  The carbon skeleton undergoes metabolism until intermediates are produced that are related to or included in the central metabolic pathway
• Amphibolic intermediates


  Depends on which point in the central metabolism they enter. Glucogenic: Increased amount of glucose, feed carbon to citric acid cycle, produces pyruvate. Ketogenic: Increased amount of ketone bodies

  
• Transamination


  1. The first step in amino acid catabolism

  2. Transfer of amino group from one amino acid to another molecule creating a new amino acid & its corresponding keto acid

  3. Amino group has to be removed first before the carbon skeleton can be metabolized

  
• Some amino acids do not undergo transamination before the catabolism of their carbon skeletons: Proline, Hydroxyproline, Threonine, Lysine

  
• There are diseases caused by problems in the catabolism of branched-chain amino acids such as leucine, isoleucine and valine that may cause diseases such as Phenylketonuria (PKU), Alkaptonuria and Maple Syrup Urine Disease (MSUD)
• Gluconeogenic Amino Acids via Oxaloacetate


  1. Aspartate and asparagine

  2. Asparagine will first lose its amino group through asparaginase and will be converted to aspartate

  3. Aspartate will go transamination and transfer its amino group to pyruvate to form alanine. Aspartate will then become oxaloacetate

  
• Gluconeogenic Amino Acids that Enter the Citric Acid Cycle via α-Ketoglutarate

  1. Glutamine & glutamate form α-ketoglutarate

  2. Glutamine will remove the amino group from its functional group and releases free ammonia

  3. Glutamate will remove its alpha amino group and gives this to pyruvate which forms alanine

  4. Glutamate → α-ketoglutarate

  
• Proline, glutamine, arginine, histidine converted to glutamate first to enter citric acid cycle

  
• Catabolism of Proline


  1. Proline Dehydrogenase catalyzes the first reaction, producing Pyrroline Carboxylate

  2. Pyrroline Carboxylate Dehydrogenase catalyzes the second reaction, producing Glutamate

  3. Glutamate then undergoes transamination to form α-ketoglutarate

  
• Catabolism of Arginine


  1. Arginine is converted to Ornithine

  2. Ornithine produces Urea by the enzyme Arginase

  3. Ornithine will undergo transamination to Glutamate Semialdehyde by Ornithine Aminotransferase

  4. Glutamate semialdehyde undergoes oxidation to glutamate

  
• Histidine has no physiologic significance but it forms histamine
• Catabolism of L-histidine to α-ketoglutarate


  1. Histidine → Urocanate (Histidase)

  2. Urocanate → Imidazolone propionate (Urocanase)

  3. Imidazolone propionate → Formiminoglutamate (Figlu) (Imidazolone propionate hydrolase)

  4. Figlu → Glutamate (Glutamate formiminotransferase)

  5. Glutamate → α-ketoglutarate

  
• Folic acid deficiency will cause increased urinary excretion of Figlu (N-Formiminoglutamate), a metabolite of histidine metabolism
• Glycine is the smallest amino acid and is metabolized using the glycine cleavage system/complex found in mitochondria of liver
• Glycine cleavage system


  1. H protein is attached to the P-protein

  2. P protein will first remove the first carbon unit from glycine and will release it as CO2

  3. Remaining part of the glycine will be attached to the H-Protein

  4. It will release its methylene group and ammonia through the enzyme T protein

  5. Remaining H protein should be oxidized back by the L protein

  
• Interconversion of serine and glycine

  1. Serine is catalyzed by glycine hydroxymethyltransferase, a reversible reaction requiring tetrahydrofolate

  2. Serine can then be converted to pyruvate

  
• Alanine


  Key gluconeogenic amino acid. In the liver, alanine can be converted to pyruvate by transamination. Pyruvate is then converted to glucose via gluconeogenesis. In the muscle, pyruvate can be converted to alanine and be brought back to the liver

  
• Glycine catabolism


  1. Remove first carbon unit from glycine

  2. Release CO2

  3. Remaining part of glycine attached to H-Protein

  4. Release methylene group and ammonia through T protein

  5. Require tetrahydrofolate as methylene group acceptor

  6. H protein oxidized back by L protein

  
• Serine


  • Converted to glycine, catalyzed by glycine hydroxymethyltransferase
  • Reversible reaction
  • Require tetrahydrofolate
  • Undergoes another reaction to produce pyruvate

  
• Alanine


  • Key gluconeogenic amino acid
  • In liver, converted to pyruvate by transamination
  • Pyruvate converted to glucose for gluconeogenesis
  • In muscle, pyruvate converted to alanine and brought back to liver
  • Direct intermediate of pyruvate metabolism

  
• Cysteine


  • Not water soluble, not well absorbed by intestine
  • Dietary cysteine mainly from breakdown of ingested protein and peptides
  • Ingested as cystine, two cysteine molecules by disulfide bond
  • Catabolized to form pyruvate through two different pathways
  • Glucogenic amino acid

  
• Threonine catabolism


  1. Threonine → Acetaldehyde + Glycine

  2. Acetaldehyde → Acetate

  3. Acetate → Acetyl CoA

  
• Threonine aldolase


  • Important enzyme for production of Acetaldehyde and Glycine

  
• Tyrosine


  • Both glucogenic and ketogenic
  • Alkaptonuria - accumulation of homogentisate, defect in homogentisate oxidase, urine darkens, arthritis and chronosis

  
• Phenylalanine


  • Must be converted to Tyrosine by phenylalanine hydroxylase
  • Phenylketonuria - defect in phenylalanine hydroxylase, hemolation of phenylalanine and deficiency of tyrosine, musty odor

  
• Tryptophan catabolism


  1. Tryptophan → N-L-Formylkynurenine

  2. N-L-Formylkynurenine → L-Kynurenine

  3. L-Kynurenine → 3-L-Hydroxykynurenine

  4. 3-L-Hydroxykynurenine → 3-Hydroxyanthranilate

  5. 3-Hydroxyanthranilate → α-Ketoadipate

  
• Hartnup disease


  Impaired intestinal and renal transport of tryptophan and other neutral amino acids, limits tryptophan availability for niacin biosynthesis
• Lysine catabolism


  1. Lysine → Saccharopine

  2. Saccharopine → L-α-Aminoadipateδ-semialdehyde

  3. L-α-Aminoadipateδ-semialdehyde → L-α-Aminoadipate

  4. L-α-Aminoadipate → α-Ketoadipate

  5. α-Ketoadipate → Glutaryl-CoA

  6. Glutaryl-CoA → Crotonyl-CoA

  7. Crotonyl-CoA → butanoyl-CoA

  
• Methionine


  • Reacts with ATP to form S-adenosyl-L-methionine (activated form)
  • Further reactions produce homocysteine
  • S-adenosyl-L-methionine is a donor of sulfhydryl group in cysteine
  • Subsequent reactions form propionyl-CoA which is converted to succinyl-CoA

  
• Branched-chain amino acids (Valine, Isoleucine, Leucine)

  • Use the enzyme branched chain α-ketoacid dehydrogenase complex
  • Complex has 5 components: E1, E2, E3, protein kinase, protein phosphatase

  
• Maple syrup urine disease

  • Rare genetic metabolic disorder
  • Defect in branched chain keto-acid dehydrogenase complex
  • Has fatal ketoacidosis, neurological derangements, mental retardation
  • Urine has maple syrup or burnt sugar odor
  • Elevated plasma and urinary levels of leucine, isoleucine and valine and their α-keto acids and α-hydroxy acids
• Specialized compounds from amino acids

  1. Coenzyme A and taurine

  2. Histamine

  3. S-adenosylmethionine

  4. Purines and pyrimidines

  5. Sphingosine and ceramides

  6. Serotonin and melatonin

  7. Catecholamines

  8. Creatinine and creatine

  9. Gamma aminobutyric acid

  
• Amino acids also serve as precursors of many nitrogen-containing compounds with physiologic importance
• May be recycled to form: nucleotides, pyrimidines & purines, hormones, neurotransmitters, porphyrins, nitric oxide