5-Amino acid modification

• Modified Amino Acids:

  • Most are formed through post-translational modification of one or more of the standard 20 amino acids
  • Some are isolated from hydrolyzates of mammalian protein
  • Some occur biologically but are not found in protein
  • All must arise through enzymatic modifications of parent amino acids after being inserted into their respective polypeptide chains
• Methylhistidine:

  • Derivative of histidine
  • Occurs in muscle protein
• Methyllysine:

  • Derivative of lysine
  • Occurs in muscle protein
• Hydroxyproline & Hydroxylysine:

  • Derivative of proline & lysine
  • Occurs in collagen
  • Collagen is the most abundant protein, found in connective tissue of blood vessels, tendons, bones, cartilages
  • Hydroxylation requires Vitamin C, deficiency of which leads to weak fibers, fragile blood vessels, hematomas, bruises, weakness
• Desmosine & Isodesmosine:

  • Formed by oxidation and crosslinking of four lysine side chains
  • Prevalent in the connective tissue elastin
• Elastin:

  • Contains desmosine and isodesmosine
  • Protein capable of undergoing a two-way stretch
  • Found in connective tissue associated with smooth muscle (e.g. blood vessels)
  • Arteries contain more elastin than veins
• Phosphothreonine, phosphotyrosine, phosphoserine:

  • Formed from phosphorylation of the hydroxyl groups contained on the side chains of threonine, tyrosine, and serine respectively
  • Mostly found on regulatory proteins
• ∂-carboxyglutamate:

  • From carboxylation of glutamic acid
  • Necessary in the production of clotting factors in the liver
  • Found in clotting factor II (prothrombin), where glutamic acid residues allow chelation of Ca++ essential to blood coagulation
• Nonprotein Amino Acids:

  • Amino acids not incorporated into proteins, but are important precursors or metabolic intermediates
  • Include ß-alanine, homocysteine, homoserine, ornithine, citrulline, taurine, GABA
• ß-alanine:

  • Building block of pantothenic acid (Vitamin B5)
• Homocysteine and homoserine:

  • Intermediates in methionine metabolism
• Ornithine and citrulline:

  • Intermediates in arginine synthesis in the hepatic urea cycle
• Taurine:

  • Discovered in ox bile in 1827
  • Formed by oxidation of the sulfhydryl group of cysteine to –SO3-, then decarboxylation
  • Required in cat's diet
  • Deficiency is associated with central retinal degeneration, blindness, dilated cardiomyopathy, reproductive failure, retarded body growth, and skeletal deformities
• ∂-Aminobutyric acid (GABA):

  • Important inhibitory neurotransmitter in CNS, formed through decarboxylation of glutamate in gray matter
  • Present in substantia nigra, globus pallidus, hypothalamus, pancreatic islet tissue, and enteric NS of gut wall
  • Promotes sleepiness, rest, satiety
• Essential Amino Acids:

  • Amino acids required in the diet
  • Not synthesized by the body
  • Have longer half-life than non-essential amino acids
  • Required to maintain protein biosynthesis
  • Negative nitrogen balance results from catabolism of unused essential amino acids following absence of one amino acid
  • Essential amino acids vary depending on species and age
• Leucine, isoleucine, and valine:

  • Branched-chain amino acids routinely oxidized in muscle tissue
• Phenylalanine:

  • Needed to produce hepatic tyrosine for catecholamine (e.g. epinephrine) synthesis in nerve tissue and thyroid hormone synthesis
• Methionine:

  • Needed for cysteine formation
• Tryptophan:

  • Used for serotonin and melatonin formation