Amino Acids

• 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.

Cautions:

• 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.

Genetics:

• 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.

Cost:

• 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.

Citrullinemia:

• 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.

Hyperargininemia:

• 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.

Homocarnosine:

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

Homocarnosinosis:

• 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.

Polyamines:

• 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.