Conversion of Amino Acids to Specialized Products PDF

CONVERSION OF AMINO ACIDS TO SPECIALIZED PRODUCTS Biochemistry Lecture, 1st Semester College of Medical and Biological Sciences University of the Immaculate Conception BIOMEDICAL IMPORTANCE Certain proteins contain amino acids that have been post-translationally modified – carboxy...

CONVERSION OF AMINO ACIDS TO SPECIALIZED PRODUCTS Biochemistry Lecture, 1st Semester College of Medical and Biological Sciences University of the Immaculate Conception BIOMEDICAL IMPORTANCE Certain proteins contain amino acids that have been post-translationally modified – carboxylation of glutamate to form γ-carboxy- glutamate→ Ca2+ binding – hydroxylation of proline → collagen triple helix – hydroxylation of lysine to 5-hydroxylysine→ stabilize maturing collagen fibers BIOMEDICAL IMPORTANCE precursors of biologic materials – heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides – Neurotransmitters → γ-aminobutyrate (GABA), 5- hydroxytryptamine (serotonin), dopamine, norepinephrine, epinephrine – neurologic and psychiatric drugs Amino Acid Metabolism L-ALPHA AMINO ACIDS ALANINE carrier of ammonia and carbons of pyruvate from skeletal muscle to liver via the Cori cycle together with glycine, constitutes a major fraction of the free amino acids in plasma ARGININE carrier of N atoms in urea biosynthesis guanidino group of arginine is incorporated into creatine conversion to ornithine carbon skeleton becomes that of putrescine and spermine ARGININE nitric oxide synthase converts one nitrogen of the guanidine group of arginine to L- ornithine and nitric oxide CYSTEINE biosynthesis of coenzyme A → reacting with pantothenate to form 4-phosphopantothenoylcysteine Taurine → displaces the coenzyme A moiety of cholyl-CoA to form taurocholic acid GLYCINE Glycine conjugation to create water- soluble metabolites (e.g. benzoate to Hippurate) → excreted in urine incorporated into creatine nitrogen and α-carbon of glycine are incorporated into the pyrrole rings and the methylene bridge carbons of heme entire glycine molecule becomes atoms 4, 5, and 7 of the purines HISTIDINE histamine – biogenic amine; functions in allergic reactions and gastric secretion Catalyzed by histidine decarboxylase HISTIDINE carnosine, ergothioneine and anserine Carnosine (β-alanylhistidine), homocarnosine (γ-aminobutyryl- histidine) – major constituents of excitable tissues, brain, and skeletal muscle Wilson disease → low urinary levels of 3-methylhistidine METHIONINE S-adenosylmethionine → principal source of methyl groups in the body from methionine and ATP catalyzed by methionine adenosyltransferase (MAT) METHIONINE decarboxylation of SAM → polyamines spermine and spermidine – cell proliferation and growth, – growth factors for cultured mammalian cells – stabilize intact cells, subcellular organelles, and membranes Catabolism of Polyamines SERINE sphingosine, purines and pyrimidines – carbons 2 and 8 of purines and the methyl group of thymine homocystinuria → genetic defects in cystathionine β- synthase (PLP dependent) – Serine + Homocysteine → Cystathionine + H2O precursor of peptidyl selenocysteine  TRYPTOPHAN serotonin (5-hydroxytryptamine) – hydroxylation by liver tryptophan hydroxylase with subsequent decarboxylation – potent vasoconstrictor and stimulator of smooth muscle contraction carcinoid (argentaffinoma) – tumor cells overproduce serotonin Melatonin → N-Acetylation of serotonin, then O-methylation in the pineal body principal normal urinary catabolites of tryptophan → 5-hydroxyindoleacetate and indole 3-acetate TYROSINE Phosphoserine, Phosphothreonine, and Phosphotyrosine phosphorylation and dephosphorylation of specific seryl, threonyl, or tyrosyl residues of proteins regulate the activity of certain enzymes of lipid and carbohydrate metabolism and proteins signal transduction cascades SARCOSINE (N-Methylglycine) occur in mitochondria catalyzed by dimethyl glycine dehydrogenase may also arise from methylation of glycine (GNMT) important sources of one- carbon units CREATINE & CREATININE Creatinine formed in muscle from creatine phosphate → irreversible, nonenzymatic dehydration, and loss of phosphate 24-hour urinary excretion of creatinine proportionate to muscle mass Glycine, arginine, and methionine synthesis completed by methylation of guanidoacetate by SAM NON-ALPHA AMINO ACIDS β-Alanine & β-Aminoisobutyrate catabolism of the pyrimidines uracil and thymine, respectively β-alanine → hydrolysis of β-alanyl dipeptides (carnosinase) β-aminoisobutyrate → transamination of methylmalonate semialdehyde  β-Alanyl Dipeptides carnosine and anserine (N- methylcarnosine) activate myosin ATPase, chelate copper, and enhance copper uptake β-Alanyl-imidazole → buffers the pH of anaerobically contracting skeletal muscle heritable disorder carnosinase deficiency → carnosinuria Homocarnosine – present in human brain at higher levels than carnosine – synthesized in brain tissue by carnosine synthetase – Homocarnosinosis → progressive spastic paraplegia and mental retardation γ-Aminobutyrate inhibitory neurotransmitter formed by decarboxylation of glutamate by L-glutamate decarboxylase 4-hydroxybutyric aciduria – defects in succinic semialdehyde dehydrogenase – presence of 4- hydroxybutyrate in urine, plasma, and cerebrospinal fluid (CSF) – mild-to-severe neurologic symptoms