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Amino acid metabolism M.F.Ullah,Ph.D COURSE TITLE: BIOCHEMISTRY 2 COURSE CODE: BCHT 202 PLACEMENT/YEAR/LEVEL: 2nd Year/Level 4, 2nd Semester Introduction to Amino- acid structure and function All 20 standard amino acid found in proteins have one α- amino group the amino group which Is attached to the carbon atom immediately adjacent to the carboxylate group Functions : build proteins that have diverse functions in all organisms- build muscles, act as biological catalysts as enzymes, structural integrity in cells and many others. * Amino acid metabolism occurs in Liver Classification of Amino- acids Based on Nutritional Requirements Essential Amino acids : Nutritionally must be present in diet because these can not be synthesized in our body; The body lacks enzymes that can synthesize these amino acids from any precursor molecules. Non-Essential Amino acids : Need not be present in diet because the body can take care of their synthesis when required or when these are deficient in the diet. Semi-essential: Body can synthesize these amino acids but not in adequate amounts to support proper growth Tabulated list of Essential/Non-Essential/Semi-essential Anino Acids Amino Acid Requirements of Humans -------------------------------------------------------------------Nutritionally Essential Nutritionally Nonessential -------------------------------------------------------------------Argininea Alanine Histidine Asparagine Isoleucine Aspartate Leucine Cysteine Lysine Glutamate Methionine Glutamine Phenylalanine Glycine Threonine Proline Tryptophan Serine Valine Tyrosine --------------------------------------------------------------------a “ Nutritionally semiessential.” Synthesized at rates inadequate to support growth of children. Protein / Amino acid Metabolism 1. Catabolic pathway of protein requires the breakdown of protein (polymer of amino acids) into amino acids by the cleavage of peptide bonds through the catalytic action of enzymes called proteases (also called as proteinases ) . 2. The amino acids then undergo metabolic degradation through two kinds of reactions: i. Transamination reaction ii. Oxidative deamination reaction Transamination Reactions Transamination: The α-amino group of an amino acid is transferred to an α-keto acid (such as αketoglutarate) to form glutamate. The enzymes that catalyze these reactions are called transaminases or aminotransferases. There are many transaminases tabulated below and the reactions catalyzed Oxidative deamination Removes α-amino group from Glutamate (amino-acid) which is released as inorganic ammonium ion (+NH4 is toxic-urea cycle) Provides α-ketoglutarate for transamination Catalysed by Glutamate Dehydrogenase +NH 4 is toxic and so it is excreted (removed) from the body in the form of urea by urea cycle. Degradation of Amino-acids Amino acids build proteins; And surplus amino-acids are not stored in our body (unlike carbohydrates and fats) but are also not excreted ! Where do they go ? Surplus amino acids are used as metabolic fuel - The α-amino group is removed by oxidative deamination and the carbon skeleton is converted into a major metabolite intermediate- -pyruvate, acetyl coA, or one of the intermediates of TCA cycle depending upon the amino acid (carbon skeleton) Stages of Amino-acid degradation Stage 1: transfer of α–amino group/ Transaminases The α-amino group of amino acids is funneled from a variety of amino acids to αKetoglutarate for conversion into ammonium ion. Important example are Alanine + Aspartate + α-ketoglutarate α-ketoglutarate Pyruvate + Glutamate Oxaloacetate + Glutamate Stage 2: Removal of α–amino group from glutamate as ammonium ion/ Glutamate dehydrogenase Glutamate + NAD+ + H2O +NH 3 + α-Ketoglutarate + NADH + H+ So in stage 1 carbon skeletons of amino acids are converted to pyruvate and intermadiates of TCA cycle for example OAA and in stage 2 the amino group of starting Amino acid is removed as ammonium ion, converting glutamate back to α-Ketoglutarate Glucogenic and ketogenic amino acids The strategy of amino acid degradation is to form metabolic intermediates that can be converted into Glucose or be oxidized by the TCA cycle. Glucogenic amino acids Amino-acids that are degraded to pyruvate, α-ketoglutarate, succinyl coA, fumarate or oxaloacetate are termed glucogenic amino-acids. Net synthesis of glucose is possible because TCA cycle intermediates and Pyruvate can be be converted to phosphoenolpyruvate and then into Glucoce (Gluconeogenesis) Ketogenic amino acids Amino acids are degraded to acetyl coA or aceto acetyl coA are termed ketogenic . No Gluconeogenesis possible because mammals lack enzymatic pathways for net conversion of aceto or aceto-acetly coA into Glucose. Glucogenic amino acids: TCA cycle intermediates or pyruvate (gluconeogensis) Example: alanine, glycine, serine Ketogenic amino acids: acetyl CoA, acetoacetyl CoA, acetoacetate Example: leucine, lysine or