You are on page 1of 35

Metabolism of Amino Acids

A. Metabolism: Proteins, Amino Acids
(Nonessential) Alanine Asparagine Aspartate Cysteine Glutamate Glutamine Glycine Proline Serine (Essential) Arginine Histidine Methionine Threonine Valine Glucogenic & Ketogenic Ketogenic tyrosine

Isoleucine Phenylalanine Tryptophan

Leucine Lysine

A. Classification of amino acid as exclusively glucogenic, glucogenic and ketogenic, or exclusively ketogenic

Tryptophan Valine Histidine Arginine Leucine








Fig. 1 B. Some students may find “PVT TIM HALL” helpful in recalling the essential AA.

Functions of Proteins 1. Enzymatic catalysis 2. Transport and storage 3. Coordinated motion – responsible for movements in the body (muscles) 4. Mechanical support – support of body - bones and muscles 5. Generation and transmission of impulses 6. Control of growth and differentiation AA - simplest form of proteins 20 AA

Characteristics of proteins 1. Have more members 2. Fundamental component of protoplasm 3. Elements in protein C, H, O, N (I & Fe) 4. Proteins are considered macromolecules, composed of a number of AA joined together by peptide bond or linkage 5. Only foodstuff when absent in the diet will cause death 6. Utilize in the body for growth

Digestion of Proteins 1. Mouth - food is chewed 2. Stomach: Gastrin - triggers chief cells to release Hcl and pepsinogen 3. Small intestines: – Secretin-stim. release of pancreatic juices – Activation of proteolytic enzymes: Trypsinogen → trypsin Chymotrypsinogen → chymotrypsin Proelastase → elastase Endo & exopeptidases → activated

Products of enz action = amino acids Dipeptides & small peptides → AA Greater amount of AA in portal blood is in the form of alanine

STOMACH • Protein digestion starts in the stomach • dietary proteins become denatured by gastric acid → important for protein digestion because proteins are poor substrates for proteases ACID ENVIRONMENT is required for action of pepsin

PEPSIN • • • • • A protease that works optimally at pH 2 a carboxyl protease acts mostly as endopeptidase does not cleave at random prefers peptide bonds formed by amino group of aromatic AA • major breakdown products are not free AA but a mixture of oligopeptides known as peptones

INTESTINE As acidic stomach contents reach duodenum → rapidly neutralized by HCO3 in pancreatic secretions. Proteolytic enzymes from pancreas include: 1. Trypsin – a serine protease – endopeptidase – specific for “CO” side of basic AA

2. Chymotrypsin – a serine protease – endopeptidase – specific for “CO” side of hydrophobic AA 1 & 2 = degrade peptones to smaller peptides 3. Carboxypeptidase A: – hydrophobic AA at “C” terminal 4. Carboxypeptidase B – basic AA at “C” terminus

PROTEIN TURNOVER • A continuous process of protein degradation into AA and re-synthesis of proteins for AA’s • 1-2% of total body protein/day: primarily for degradation of muscle proteins RDA = 30 60 gm proteins/day PROTEIN QUALITY: – Proportion of essential AA in food relative to their proportion in proteins being synthesized

• excess AA are not stored • those not incorporated into new proteins are rapidly degraded • unlike CHO’s and lipids, proteins and AA are not stored by the body • proteins are present in all cells • some of the body’s proteins can be mobilized during fasting or starvation → “C” skeletons of AA’s are burned for energy or converted to glycogen or TG → stored.

“Amino acid pool”: • is not a storage place for AA’s • is a convenient way to indicate that small amounts of AA’s are present in cells or circulate in blood During starvation: • much of plasma proteins (esp albumin) are utilized first • rapidly metabolizing tissues (liver, pancr, intesti mucosa) - tend to lose their proteins quickly • muscle is slow to yield AA’s

MAJOR PATHWAYS FOR DEGRADATION OF INTRACELLULAR PROTEINS 1. Lysosomal • membrane-associated proteins • long-lived intracellular proteins • cathepsins 2. Cytosolic • require ubiquitin, ATP • for abnormal and short-lived proteins

WHAT FACTORS TARGET A PROTEIN FOR DEGRADATION? • For proteins in circulation: – loss of sialic acid moiety from non-reducing ends of oligosaccharide chains → signal degradation asialated glycroproteins → recognized by receptors in liver cells → internalized → degraded in lysosomes by cathepsins

THE 20 AMINO ACIDS USED FOR BUILDING PROTEIN CHAINS: Aliphatic nonpolar side chains: gly leu val ala ile Aromatic side chains: phe tyr trp Hydroxyl-containing side chains: ser thr

Acidic side chains: asp (d) glu (e) Amidic amino acids: asn (n) gln (q) Basic side chains: lys arg his Sulfur-containing side chains: cys met Imino acid: pro

Common AA’s = those AA’s for which at least one specific codon exists in the genetic code Derived AA’s = in proteins are formed from one of the common AA’s after the common AA has been incorporated into protein structure Aromatic AA’s: Phe contains benzene ring Tyr contains phenol grp Trp = R grp contains a heterocyclic structure indole nucleus * In all 3 AA’s → the aromatic moiety is attached to the a-c thru a methylene (-CH2)

Name • Albinism • Alkaptonuria • Argininosuccinic acidemia • Homocystinuria • Maple syrup urine disease • Phenylketonuria • Hypervalinemia • Cytinosis • • • • Cystinuria Hartnup’s disease Histidinemia Isovaleric acidemia Defective Enzyme or Process • Tyrosine 3-monooxygenase • Homogentisate 1,2-dioxygenase • Argininosuccinate lyase • Cystathionine β -synthase • Branched-chain-α -ketoacid dehydrogenase • Phenylalanine 4-mono oxygenase • Valine transaminase • Storage and/ore release of cystine from lysosomes • Renal and intestinal transport of cysteine • Renal transport of neutral AA • Histidine ammonia lyase • Isovaleryl CoA dehydrogenation

Disorders Hyperammonemia-Type I Hyperammonemia-Type II Citrullinemia Arginosuccinic aciduria Hyper argininemia Enzyme Defect Carbamoyl phosphate synthetase Ornithine transcarbamylase Arginosuccinate synthetase Arginosuccinase arginase

CONVERSION OF AMINO ACIDS TO SPECIALIZED PRODUCTS 1. Glycine a. A-carbon & N atom → used for synthesis of porphyrin moiety of Hb b. Entire gly mol → forms position 4,5,7 of purine skeleton c. gly + cholic acid → glycocholic acid (bile acids) d. gly + sam → sarcosine (n-methyl-gly) component of creatine

2. Alanine • Ala + gly → amino N2 in human plasma ∀ β-ala + his → present in carnosine
(major % in humans) (skel musc dipeptide)

3. Arginine - formamidine donor for creatine synthesis in primates 4. Ornithine a. plays a role in urea biosynthesis b. precursor or mammalian polyamines spermidine & spermine

5. Tryptophan • precursor of serotonin CO2 5 HT 5 hydroxytryptamine (serotonin)

oxid deamination Serotonin 5 hydroxyindole-acetate mondamine oxidase

6. Tyrosine • precursor of epinephrine & norepinephrine • precursor of thyroid hormones - triiodothyronine (T3) & thyroxine (T4) 7. Creatine & Creatinine Creatine - present in muscle, brain, blood as phosphocreatine free creatine – n’ly present in urine (traces) – synthesis involves 3 AA’s gly, arg, met

8. Gaba - γ-aminobutyrate • formed fr glutamate by decarboxylation • catabolism involves transamination → succinate semi-aldehyde → succinate


Amine Acetylcholine Norepinephrine Epinephrine Serotonin Gaba Histamine Spermine Creatine

Amino Acid Precursor Ser, met Tyr Tyr, met Trp Glu His Ornithine met Arg, gly, met

Distinguishing Features of Pathways Sam is methylating agent L-dopa is intermediate & precursor of melanins Sam-dependent transaminase activated by glucocorticoids 5-hydroxy trp is intermediate (5-HT) Decarboxylation reaction Decarboxylation reaction Spermidine is intermediate Guanidino grp transferred to gly

Glucogenic alanine arginine asparazine aspartic acid cysteine glutamic acid glutamine glycine histidine methionine proline serine threonine tryptophan valine Ketogenic leucine lysine tryptophan

Ketogenic and glycogenic phenylalanine tyrosine

ESSENTIAL AND NONESSENTIAL AMINO ACIDS Essential Methionine Arginine Phenylalanine Threonine Valine Tryptophan Histidine Isoleucine Leucine Lysine Nonessential Glutamate Glutamine Proline Aspartate Asparagine Alanine Glycine Serine Tyrosine Cysteine