Amino Acids

Amino acids:

    • The genetic code specifies 20L amino acids which are the building blocks of protein. There are 20 alpha-amino acids that combine to make 50,000 to 100,000 different proteins in the body.
    • Organic compounds that can contain an amino carboxyl (-COOH) and a (-NH2) group.
    • There are both one-and three-letter abbreviations for each amino acid that can be used to represent the amino acids in peptides. Some proteins contain additional amino acids that arise by modification of an amino acid already present in a peptide.
    • An example is the conversion of peptidyl proline and lysine to 4-hydroxyproline and 5-hydroxylysine; converting peptidyl glutamate to γ-carboxyglutamate; and the methylation, formylation, acetylation, prenylation, and phosphorylation of certain aminoacyl residues.
    • By altering protein solubility, stability, and interaction with other proteins it creates biological diversity.
    • Both D-amino acids and non-α-amino acids occur in nature, L--Amino Acids only Occur in Proteins with the exception of glycine, the α-carbon of amino acids is chiral.
    • All amino acids possess at least two weakly acidic functional groups, RNH3 + and RCOOH. Many also possess additional weakly acidic functional groups such as OH, SH, guanidino, or imidazole groups.
    • The pKa values of all functional groups of an amino acid dictate its net charge at a given pH. pI is the pH at which an amino acid bears no net charge and thus does not move in a direct current electrical field.
    • Of the biochemical reactions of amino acids, the most important is the formation of peptide bonds.
    • The R groups of amino acids determine their unique biochemical functions. Amino acids are classified as basic, acidic, aromatic, aliphatic, or sulfur-containing based on the properties of their R groups.
    • Peptides are named for the number of amino acid residues present and as derivatives of the carboxyl-terminal residue. The primary structure of a peptide is its amino acid sequence, starting from the amino-terminal residue.
    • The partial double-bond character of the bond that links the carbonyl carbon and the nitrogen of a peptide renders four atoms of the peptide bond coplanar and restricts the number of possible peptide conformations.
    • All vertebrates can form certain amino acids from amphibolic intermediates or from other dietary amino acids. The intermediates and the amino acids to which they give rise are α-ketoglutarate (Glu, Gln, Pro, Hyp), oxaloacetate (Asp, Asn) and 3-phosphoglycerate (Ser, Gly).
    • Cysteine, tyrosine, and hydroxylysine are formed from nutritionally essential amino acids. Serine provides the carbon skeleton and homocysteine the sulfur for cysteine biosynthesis. Phenylalanine hydroxylase converts phenylalanine to tyrosine.
    • Neither dietary hydroxyproline nor hydroxylysine is incorporated into proteins because no codon or tRNA dictates their insertion into peptides.
    • Peptidyl hydroxyproline and hydroxylysine are formed by hydroxylation of peptidyl proline or lysine in reactions catalyzed by mixed-function oxidases that require vitamin C as a cofactor. The nutritional disease scurvy reflects impaired hydroxylation due to a deficiency of vitamin C.
    • Selenocysteine, an essential active site residue in several mammalian enzymes, arises by co-translational insertion of a previously modified tRNA.
    • Human subjects degrade 1–2% of their body protein daily at rates that vary widely between proteins and with a physiologic state. Key regulatory enzymes often have short half-lives.
    • Proteins are degraded by both ATP-dependent and ATP-independent pathways. Ubiquitin targets many intracellular proteins for degradation.
    • Liver cell surface receptors bind and internalize circulating a sialoglycoprotein destined for lysosomal degradation.
    • Ammonia (NH3) is highly toxic. Fish excrete NH3 directly; birds convert NH3 to uric acid. Higher vertebrates convert NH3 to urea.
    • Transamination channels α-amino acid nitrogen into glutamate. L-Glutamate dehydrogenase (GDH) occupies a central position in nitrogen metabolism.
    • Glutamine synthase converts NH3 to nontoxic glutamine. Glutaminase releases NH3 for use in urea synthesis.
    • NH3, CO2, and the amide nitrogen of aspartate provide the atoms of urea.
    • Hepatic urea synthesis takes place in part in the mitochondrial matrix and in part in the cytosol.
    • Inborn errors of metabolism are associated with each reaction of the urea cycle.
    • Changes in enzyme levels and allosteric regulation of carbamoyl phosphate synthase by N-acetylglutamate regulate urea biosynthesis.
    • In addition to their roles in proteins and polypeptides, amino acids participate in a wide variety of additional biosynthetic processes.
    • Glycine participates in the biosynthesis of heme, purines, and creatine and is conjugated to bile acids and to the urinary metabolites of many drugs.
    • In addition to its roles in phospholipid and sphingosine biosynthesis, serine provides carbons 2 and 8 of purines and the methyl group of thymine.
    • S-Adenosylmethionine, the methyl group donor for many biosynthetic processes, also participates directly in spermine and spermidine biosynthesis.
    • Glutamate and ornithine form the neurotransmitter γ-aminobutyrate (GABA).
    • The thioethanolamine of coenzyme A and the taurine of taurocholic acid arise from cysteine.
    • Decarboxylation of histidine forms histamine and several dipeptides are derived from histidine and β-alanine.
    • Arginine serves as the formamidine donor for creatine biosynthesis, participates in polyamine biosynthesis, and provides the nitrogen of nitric oxide (NO).
    • Important tryptophan metabolites include serotonin, melanin, and melatonin.
    • Tyrosine forms both epinephrine and norepinephrine, and its iodination forms thyroid hormone.

Amino Acid Metabolism

• The α-amino group is removed by transamination

• Transaminases catalyze the reaction:

• α-amino acid + α-ketoglutarate ⇔ α-keto acid + glutamate

• Glutamate is degraded by glutamate dehydrogenase, releasing NH4+ (→ Urea Cycle)

• The carbon skeleton is converted to one or more metabolic intermediates, or for use as metabolic fuel

– Amino acids which are degraded to pyruvate, α-ketoglutarate, succinyl CoA, fumarate and oxaloacetate are called ‘glucogenic’(directly into gluconeogenesis)

– Those degraded to acetyl CoA or acetoacetyl CoA are termed ‘ketogenic’ (produce ketone bodies)


    • Build proteins to structure skin, membranes, muscles, organs, and bones.
    • Some act as neurotransmitters, the chemicals that ferry information from one nerve cell to another. Others are precursors of neurotransmitters, involved in creating the compounds that do the transmitting.
    • Are the foundation for certain hormones, such as insulin, help vitamins and minerals do their job.
    • These occur in mirror images, left-hand forms are known as "L" and right hand as "D".
    • L Amino acids come from food which is the type you want to buy. If labeled 'free-form" are easily absorbed into the bloodstream and don't have to be digested.
    • Several free L-α-amino acids play an important role in metabolic processes, such as ornithine, citrulline, and argininosuccinate in urea synthesis; tyrosine in the formation of thyroid hormones; and glutamate in neurotransmitter biosynthesis.


    • Do not take without Doctors guidance.
    • Do not take individual Amino acids for more than 2 to 3 months at a time, can persist long after taken.
    • Should only be taken for a specific reason.


    • Low in particular amino acids. Example-Phenylketonuria-a hereditary condition and can't metabolize phenylalanine properly. If left untreated, mental retardation and poor muscle coordination can result.


    • It is more economical to increase the amount of protein in your diet than to buy mixtures of amino acid supplements.

Essential Amino Acids:

Nine amino acids are classified as essential because your body is unable to produce them and you must get them from eating foods that supply them. Meat, poultry, fish, eggs, milk, cheese, yogurt, and soy are complete proteins because they provide us will all nine. Other sources are beans, legumes, peas, seeds, tofu, and nuts.

    1. Histidine
    2. Isoleucine
    3. Leucine
    4. Lysine
    5. Methionine
    6. Phenylalanine
    7. Threonine
    8. Tryptophan
    9. Valine

Nonessential Amino Acids:

The other 11 amino acids are considered nonessential, we don't need them from foods because most bodies produce them. Our bodies use essential amino acids to make these.

    1. Alanine
    2. Arginine
    3. Asparagine
    4. Aspartic Acid
    5. Cysteine
    6. Glutamic Acid
    7. Glutamine
    8. Glycine
    9. Proline
    10. Serine
    11. Tyrosine

Branched-chain amino acids (BCAAs)

  • Branched-chain amino acids (BCAAs) Include 3 essential amino acids: leucine, isoleucine, and valine.
  • Each branched amino acid have different metabolic paths: Valine goes into carbohydrates; leucine into fats; isoleucine into both. The different requirements are: 12 mg/kg for valine, 14 mg/kg leucine and 16 mg/kg isoleucine.
  • Deficiency symptoms: Valine has neurological defects in the brain; isoleucine has muscle tremors.
  • BCAAs are located in muscles and are broken down and used for energy during prolonged exercise. Bodybuilders and athletes often take BCAAs to improve performance and prevent muscle breakdown during endurance training.
  • Aromatic amino acids (AAA) are increased during energy production and alertness and include tyrosine, tryptophan, phenylalanine, and methionine.
  • Responsible for- aid in biochemical components that are essential in the body; production of energy; brain stimulation; alertness.
  • Low BCAA (Branched Chain Amino Acids) often go hand and hand with low plasma alanine, which could be due to muscle metabolism.
  • Patients with liver disease such as cirrhosis, extrahepatic biliary atresia hepatitis, hepatic coma or portacaval shunt often have decreased BCAA. Valine, in particular, may be beneficial for an ailing liver.
  • BCAA and AAA need to be balanced so proper levels are needed for absorption into the brain. Supplementing with BCAA, vitamin B6 and zinc can aid in keeping the BCAA: AAA balance.
  • BCAA side effects- Leucine exacerbates pellagra which can cause psychosis and increases excretion of urinary niacin; Leucine possibly lowers serotonin and dopamine in the brain; taking 3g of isoleucine with niacin can clear the psychosis caused by leucine in schizophrenic patients; Isoleucine has potential to be an antipsychotic treatment.

Functional Groups Dictate the Chemical Reactions of Amino Acids:

    • Each functional group of an amino acid exhibits all of its characteristic chemical reactions.
    • For carboxylic acid groups, these reactions include the formation of esters, amides, and acid anhydrides; for amino groups, acylation, amidation, and esterification; and for OH and SH groups, oxidation and esterification.

Amino Acid Sequence Determines Primary Structure

    • The primary structures are the number and order of all of the amino acid residues in a polypeptide constitute.
    • Aminoacyl residues are the amino acids present in peptides which are named by replacing the -ate or -ine suffixes of free amino acids with -yl (eg, alanyl, aspartyl, tyrosyl). Peptides are named as derivatives of the carboxyl-terminal aminoacyl residue. For example, Lys-Leu-Tyr-Gln is called lysyl-leucyl-tyrosyl-glutamine.
    • The -ine ending on glutamine indicates that its α-carboxyl group is not involved in peptide bond formation.

Some Peptides Contain Unusual Amino Acids:

    • In humans, peptide hormones often only have the α-amino acids of proteins which are linked by standard peptide bonds.
    • Other peptides may contain protein amino acid derivatives, non-protein amino acids or amino acids linked by an atypical peptide bond. The amino-terminal glutamate of glutathione, which is involved in protein folding and xenobiotics metabolism which is linked to cysteine by a non-α peptide bond.
    • The amino-terminal glutamate of thyrotropin- Glu Lys Ala Gly Tyr His Ala -- -- (, , ) releasing hormone (TRH) is cyclized to pyroglutamic acid, and the carboxyl group of the carboxyl-terminal prolyl residue is amidated.
    • Peptides elaborated by fungi, bacteria, and lower animals can contain non-protein amino acids.
    • Antibiotics tyrocidine and gramicidin S are cyclic polypeptides which contain D-phenylalanine and ornithine.
    • Heptapeptide opioids dermorphin and deltophorin contain D-tyrosine and D-alanine in the skin of South American tree frogs

Peptides Are Polyelectrolytes:

    • The peptide bond is uncharged at any pH of physiologic interest.
    • Formation of peptides from amino acids is therefore accompanied by a net loss of one positive and one negative charge per peptide bond formed.
    • Peptides nevertheless are charged at physiological pH owing to their carboxyl and amino terminal groups and, where present, their acidic or basic R groups. As for amino acids, the net charge on a peptide depends on the pH of its environment and on the pKa values of its dissociating groups.

The Peptide Bond Has Partial Double-Bond Character:

    • Although peptides are written as if a single bond linked the α-carboxyl and α-nitrogen atoms, this bond, in fact, exhibits partial double-bond character: There thus is no freedom of rotation about the bond that connects the carbonyl carbon and the nitrogen of a peptide bond.
    • The imposed semi-rigidity of the peptide bond has important consequences for higher orders of protein structure.

Noncovalent Forces Constrain Peptide Conformations:

    • The physiologically active conformation reflects the amino acid sequence, steric hindrance, and noncovalent interactions (eg, hydrogen bonding, hydrophobic interactions) between residues.
    • Common conformations include α-helices and β-pleated sheets.

Metabolic Disorders Are Associated With Each Reaction Of The Urea Cycle:

    • Metabolic disorders of urea biosynthesis, while extremely rare, illustrate four important principles:
      1. Defects in any of several enzymes of a metabolic pathway enzyme can result in similar clinical signs and symptoms.
      2. The identification of intermediates and of ancillary products that accumulate prior to a metabolic block provides insight into the reaction that is impaired.
      3. Precise diagnosis requires a quantitative assay of the activity of the enzyme thought to be defective.
      4. Rational therapy must be based on an understanding of the underlying biochemical reactions in normal and impaired individuals.
      • All defects in urea synthesis result in ammonia intoxication. Intoxication is more severe when the metabolic block occurs at reactions 1 or 2 since some covalent linking of ammonia to carbon has already occurred if citrulline can be synthesized.
      • Clinical symptoms common to all urea cycle disorders include vomiting, avoidance of high-protein foods, intermittent ataxia, irritability, lethargy, and mental retardation.
      • The clinical features and treatment of all five disorders discussed below are similar.
      • Significant improvement and minimization of brain damage accompany a low-protein diet ingested as frequent small meals to avoid sudden increases in blood ammonia levels.

Hyperammonemia Type 1:

    • A consequence of carbamoyl phosphate synthetase I deficiency (reaction produces this X chromosome-linked deficiency).
    • The mothers also exhibit hyperammonemia and an aversion to high-protein foods.
    • Levels of glutamine are elevated in the blood, cerebrospinal fluid, and urine, probably due to enhanced glutamine synthesis in response to elevated levels of tissue ammonia.


    • In this rare disorder, plasma and cerebrospinal fluid citrulline levels are elevated and 1–2 g of citrulline are excreted daily.
    • Citrulline and argininosuccinate, which contain nitrogen destined for urea synthesis, serve as alternative carriers of excess nitrogen. Feeding arginine enhanced excretion of citrulline in these patients. Similarly, feeding benzoate diverts ammonia nitrogen to hippurate via glycine.
    • This relatively infrequent condition (estimated frequency 1:62,000) probably is familial.

Hyperammonemia Type 2:

    • A deficiency of ornithine transcarbamylase.

Argininosuccinic Acid Uri:

    • A rare disease with elevated levels of argininosuccinate in blood, cerebrospinal fluid, and urine is associated with friable, tufted hair (trichorrhexis nodosa).
    • Both early-onset and late-onset types are known.
    • The metabolic defect is the absence of argininosuccinase.
    • Diagnosis by measurement of erythrocyte argininosuccinase activity can be performed on umbilical cord blood or amniotic fluid cells.
    • As for citrullinemia, feeding arginine and benzoate promotes nitrogen excretion.


    • This defect is characterized by elevated blood and cerebrospinal fluid arginine levels, low erythrocyte levels of arginase, and a urinary amino acid pattern resembling that of lysine-cystinuria.
    • This pattern may reflect competition by arginine with lysine and cysteine for reabsorption in the renal tubule.
    • A low-protein diet lowers plasma ammonia levels and abolishes lysine-cystinuria.

Gene Therapy Offers Promise for Correcting Defects in Urea Biosynthesis:

    • Gene therapy for rectification of defects in the enzymes of the urea cycle is an area of active investigation.
    • Encouraging preliminary results have been obtained, for example, in animal models using an adenoviral vector to treat citrullinemia.

Alanyl Dipeptides:

    • The β-alanyl dipeptides carnosine and anserine (N-methyl carnosine) activate myosin ATPase, chelate copper, and enhance copper uptake.
    • β-Alanyl-imidazole buffers the pH of anaerobically contracting skeletal muscle.
    • Biosynthesis of carnosine is catalyzed by carnosine synthetase in a two-stage reaction that involves initial formation of an enzyme-bound acyl-adenylate of β-alanine and subsequent transfer of the β-alanyl moiety to L-histidine.
    • Hydrolysis of carnosine to β-alanine and L-histidine is catalyzed by carnosinase.
    • The heritable disorder carnosinase deficiency is characterized by carnosinemia.


    • Present in the human brain at higher levels than carnosine is synthesized in brain tissue by carnosine synthase. Serum carnosinase does not hydrolyze homocarnosine.


    • A rare genetic disorder is associated with progressive spastic paraplegia and mental retardation.

Phosphorylated Serine, Threonine, & Tyrosine:

    • The phosphorylation and dephosphorylation of seryl, threonyl, and tyrosyl residues regulate the activity of certain enzymes of lipid and carbohydrate metabolism and the properties of proteins that participate in signal transduction cascades.

Ornithine & Arginine:

    • Arginine is the formamidine donor for creatine synthesis and via ornithine to putrescine, spermine, and spermidine.
    • Arginine is also the precursor of the intercellular signaling molecule nitric oxide (NO) that serves as a neurotransmitter, smooth muscle relaxant, and vasodilator. Synthesis of NO, catalyzed by NO synthase, involves the NADPH-dependent reaction of L-arginine with O2 to yield L-citrulline and NO.


    • The polyamines spermidine and spermine function in cell proliferation and growth, are growth factors for cultured mammalian cells, and stabilize intact cells, subcellular organelles, and membranes.
    • Pharmacologic doses of polyamines are hypothermic.