Amino Acids: Structure, Chirality, Classification, and Biological Roles

Slide #4 Amino Acids Amino acid: a compound that contains both an amino group and a carboxyl group composed from α-carbon to which Hydrogen atom, Rgroup, α- amino group and α- carboxyl group are attached. • The α-amino acid: the amino group is attached to the α-carbon. • Although amino acids are commonly written in the unionized form, they are more properly written in the zwitterion form: O R- CH-COH O R- CH-CO N H3 + N H2 unionized form zwitterion Sheet note #1 →Amino acid contains amino acid group (α-amino group), carboxyl group (α-carboxyl group) and carbon group (α-carbon). → Amino acids are usually written as neutral structure which means that there is no net charge, positive or negative. (the correct structure of amino acids when the positive and negative charge written) Slide #5 Chirality of Amino Acids With the exception of glycine, all protein-derived amino acids are chiral and have at least one asymmetric (chiral) carbon (normally the α-carbon). - COO α- carbon ‫׀‬ + H - C - NH3 ‫׀‬ R Sheet note #2 →Asymmetric (chiral) carbon atom: is carbon atom which connects to 4 different groups. R Group(side chine (such as H or any group) →Glycine is the smallest amino acid and it’s an exception (doesn’t have . a chiral carbon) because it has 2 hydrogen atoms around the carbon. Slide #6 The three-dimensional (3D) shape of an AA can be represented in different ways: 2 Sheet note #3 →The 3D shape of an AA can be represented in 3 ways: 1. 3D structure: The carboxyl group and the amino group are on the plane of the paper, side chain above and hydrogen atom behind. 2. Ball and stick model: Amino acids are tetrahedral in structure. 3. Fischer projection (straight formulas) means the configuration around the atom( which H at left and R group at below ) Slide #7 Chirality of Amino Acids • Chiral amino acids have two stereoisomers (=optical isomers=different spatial arrangement of atoms around chiral carbon). • The mirror-image stereoisomers are called enantiomer. • Two forms of enantiomers: L- & D- forms. • The majority of amino acids have the Lconfiguration at the α-carbon. C O OH C O O+ N H3 + H 3N CH3 H CH3 D-Alanine L-Alanine (Fischer projections) Sheet note #4 →Isomers: similar to each other →There are 2 forms of configuration: 1. L-Alanine: When the amino group is to the left in fischer projection. 2. D-Alanine: When the amino group is to the right in fischer projection. Slide #8 Comparison of the stereochemistry (3D structure) of alanine and glyceraldehyde (Fischer projection formulas). Sheet note #5 the naturally occurring form →The standard or the reference of amino acids is glyceraldehyde. CO O H →We have L-Glyceraldehyde (when the OH group is at the left in fischer projection) and D-Glyceraldehyde (when the OH group is at the right in fischer projection). →The D-Glyceraldehyde is the reference for carbohydrate, so the naturally occurring glyceraldehyde (sugars) are D configuration. →The naturally occurring amino acids are L configurations. N H3 + CO O + H 3N CH 3 the naturally occurring form CH 3 D-Alanine L-Alanine CHO CHO H OH HO H CH 2 O H CH 2 O H D-Glyceraldehyde L-Glyceraldehyde Slide #9 • In most cases, D-amino acids are toxic(not find in protein) • They occur in nature in antibiotics and bacterial cell walls. 3 H Slide #10 20 Protein-Derived a.a Sheet note #6 →Amino acids are classified according to nonpolar side chains into 9 amino acids. →There are subdivisions for these 9 amino acids: 1.Branched chain amino acids which are: valine, leucine and isoleucine. 2.Sulfur containing amino acids which are: methionine and cysteine (but cysteine has a polar side chain). 3.Aromatic amino acids which are: phenylalanine , tryptophan and tyrosine (but tyrosine has a polar side chain). 4.Cyclic amino acid which is proline (the only one). the backbone of all amino acids (H,COOH,NH3) Slide#11 Sheet note #7 →There is subdivision for these 7 amino acids: 1. Hydroxyl containing amino acids which are : serine, threonine and tyrosine (in enzyme, substrate, active side) 4 Slide #12 Slide #13 ➢ Basic side chains (predominant form at pH 7.0) arginine (arg, R) NH2 + H2 NCNHCH2 CH2 CH2 lysine (lys, K) histidine (his, H) N CH2 - N a.a. may be classified as aliphatic or aromatic: • Aliphatic a.a have R-group with hydrogen chain. • Aromatic a.a have benzene ring in R-group. Sheet note #8 →basic side chain amino acids contain neutral positive charge. H + H3 NCH 2 CH 2 CH 2 CH 2 Slide #14 Sheet note #9 →The 20 amino acids are classified into 2 groups: 1. 10 Essential amino acids, they are : 3 from branched chain (isoleucine, leucine, valine), 3 from basic side chain (arginine, lysine , histidine ), 2 from aromatic amino acids (phenylalanine, tryptophan), 1 from sulfur containing amino acids (methionine) and the last one is threonine. • All the 10 essential amino acids are essential in children. • With the exception of arginine and hitidine (because they can be synthesized in adults), the remaining 8 essential amino acids are essential in adults. 2. 10 nonessential amino acids 5 Slide #15 Note these structural features: 1. For 19 of the 20, the α-amino group is primary; for proline, it has secondary amine (called imino acid). 2. With the exception of glycine, amino acids are chiral. 3. Glycine is the smallest amino acid. 4. Isoleucine and threonine contain a second chiral carbon. 5. Amino acids are referred to by three-letters abbreviations or one -letter (the three abbreviation it important to save) Sheet note #10 →Essential amino acids: Are the amino acids which the body can’t synthesize (they must be supplied by food), the deficiency of one of them causes diseases and their origin is animal-related. →Nonessential amino acids: Are the amino acids which the body can synthesize, the deficiency of one of them doesn’t cause disease and their origin is plant-related. →We usually use the 3-letters abbreviation which is a part of amino acid's name. 6 Slide #16 Uncommon Amino Acids • Each example is derived from a common amino acid by the modification shown in color. • Hydroxylysine and hydroxyproline are found only in a few connective tissues such as collagen. Sheet note #11 →Uncommon amino acids = modified amino acids. →Hydroxylysine and hydroxyproline are important for collagen formation, they need vitamin C and their deficiency causes Scurvy disease. →Thyroxine is a thyroid hormone. Slide #17 Scurvy The onset of symptoms depends on how long it takes for the person to use up their limited stores of vitamin C. The human body is unable to make vitamin C. For example, if diet includes no vitamin C at all, the average onset of symptoms is about four weeks. 7 Slide #18 Thyroxine –T4 (modified tyrosine) • Only in the Thyroid Gland. • The main hormone secreted into the bloodstream by the thyroid gland. • It plays vital roles in digestion, heart and muscle function, brain development and maintenance of bones. Sheet note #13 →Ornithine is one of the uncommon amino acids (which aren't found in proteins). →Ornithine is one of the amino acids which are found in urea cycle. →At the final step in urea cycle (the step of urea formation), the arginine is broken down into urea and ornithine. Slide #19 Ornithine is one of the three amino acids involved in the Urea cycle. It is a nonprotein amino acid (not used to create proteins). Sheet note #14 →Ornithine is one of the uncommon amino acids (which aren't found in proteins). →Ornithine and Sertraline are the modified amino acids which are found in urea cycle. →At the final step in urea cycle (the step of urea formation), the arginine is broken down into urea and ornithine. Slide #20 Amino Acids & Neurotransmitters Sheet note #15 →Serotonin (5-HT) is said to be the hormone of happiness because it helps to relax, sleep and maintain mood balance. 8 Slide #21 The high concentration of tryptophan in milk protein may mildly elevate the levels of serotonin, which relaxes the brain. Serotonin is regarded as a chemical that is responsible for maintaining mood balance, and that a deficit of serotonin leads to depression. The tryptophan in milk might make you sleepy, whereas the tyramine in cheese should wake you up. Sheet note #16 →Milk has high concentration of tryptophan, because of that children in the past were told to drink milk before sleeping to help them fall asleep without waking up at night and annoying their families. SLIDE #22 , * Parkinson's disease A degenerative condition causing tremor and motor impairment, is caused by a loss of dopamine-secreting neurons in an area of the midbrain called the substantia nigra Phe L-dopa Dopamine Epinephrine Norepinephrine 9 Sheet note #17 phenylalanine is an essential amino acid. → Tremor and motor impairment →Dopamine, epinephrine and norepinephrine are important neurotransmitters. →Parkinson’s disease is caused by the lack of neurotransmitters and treated by giving L-dopa which converts to dopamine and so on. 10