Ali Yaghi مها أبو عجمية. Mamon Ahram

Transcription

1 13 Ali Yaghi مها أبو عجمية Mamon Ahram 0 P a g e

2 This sheet is the last sheet we are supposed to study for the midterm exam. Let s begin. Biological significance of amino acids: Amino acids are used for physiological functions, they are used by themselves, or as precursors for other important molecules physiologically. They make hormones, neurotransmitters and peptides. They also might be neurotransmitters themselves, or they might be used for metabolism. Metabolism: At the beginning of the day, the first thing metabolized is sugars (glycogen), then if you don't eat food, the lipids get metabolized. After a week of without eating food, the body breaks proteins in order to use amino acid as an energy source. Note: *Benzene ring makes Phenylalanine * Phenol makes Tyrosine * Indole makes Tryptophan *Imidazole makes Histidine *Guanidino makes Arginine Amino acids as precursors: Amino acid Tyrosine Catecholamine Tyramine Melanin Thyroxine Tryptophan Serotonin Histidine Histamine Melatonin Glutamate gama-gaba Gama- Carboxyglutamate Arginine Nitric Oxide Lysine and Proline Collagen 1 P a g e

3 Tyrosine: 1- Catecholamines (neurotransmitters). they are called so because they have the ring structure catechol. Tyrosine makes dopamine, dopamine can be converted into nor epinephrine, nor epinephrine makes epinephrine (adrenalin). They are involved in fight or flight reactions. 2- Thyroxine(hormone). 3- Melanin (skin color). Melanin is two types: Eumelanin (dark skin and hair colour) + Pheomelanin (red skin and hair colour). 4- Tyramine (very close to epinephrine in function because it is involved in extruding energy). Tyramine is found in eggs and cheese omelet. Tryptophan: 1- Serotonin (neurotransmitter- sedative). It is the substance that makes us feel happy. 2- Melatonin: is used for determination of day and night. Doctors recommend taking melatonin pills to come over jet lag. 2 P a g e

4 Note: Milk is full of tryptophan. Histidine: Functions of Histamine: Regulates physiological function in the gut Acts as a neurotransmitter Causes allergic symptoms (a major cause for asthma) Contributes to inflammatory response Causes constriction of smooth muscle Glutamate: 1- gama- aminobutyricacid (GABA): Inhibitory neurotransmitter (CNS). 2- γ-carboxyglutamate residue. Glutamate is also very important in blood clotting. Glutamate gets modified by adding a carboxylic group to form γ- carboxyglutamate residue. It is called Gama because we added carboxylate group to Gama carbon. Note: Vitamin K is needed for this process. Arginine It is precursor for nitric oxide neurotransmitter (hormone- signalling molecule), which is a gas. Functions of NO: 3 P a g e

5 a-vasodilation. b- inhibition of platelet adhesion. c- inhibition of leukocyte adhesion. d- anti -proliferative action. e-scavenging superoxide anion (anti-inflammatory). Note: NO s half-life is very short. Lysine and proline: Both are hydroxylated and become hydroxyl lysine and hydroxyl proline. They are part of collagen structure. Ionization of amino acids At physiological ph, every group has its own pka. Amino group has positive charge, carboxyl group has negative charge. Zwitterion: a molecule with two opposite charges and a net charge of zero. 4 P a g e

6 Isoelectric point: It is the ph when the molecule is in the zwitterionic form (when the total charge of a molecule is zero). Protonation and ionization: When the carboxylic group is protonated, it isn't ionized(cooh), but when the amino group is portonated, it is ionized(nh3+), and vice versa. The effect of the ph over the amino acid: When the ph is below the pka for carboxyl group, the carboxyl group is protonated, and the amino group is also protonated. As a result, the net charge for the molecule is +1. When the ph is above the ph for the amino group, the amino group is deprotonated (unprotonated as the doctor said), so is for carboxyl group. The net charge for the molecule at this situation is -1. When the ph is between 2 and 9, the amino group is protonated, and the carboxyl group is deprotonated. The net molecule charge is Zero. This is called zwitterions. Note: pka for carboxyl group is around 2, and for amino group is around 9. 5 P a g e

7 1- The point of intersection between the red curve and the blue one represents the pka of the carboxyl group in the amino acid. 2- The point of intersection between the blue curve and the green one represents the pka of amino group. Notes: *Amino acids have buffering capacities. *Amino acids in its different structures (protonated and de protonated) can be considered as acids and their conjugate bases. Isoelectric Point The ph where the net charge of a molecules such as an amino acid or protein is zero is known as isoelectric point or pi. For the nonpolar and polar amino acids with two pka s, the isoelectric point is calculated by taking the numerical average of the carboxyl group pka and the amino group pka. 6 P a g e

8 pi of the amino acids Nine of the 20 amino acids have ionizable side chains. These amino acids are: tyrosine (hydroxyl), cysteine (thiol), Arginine (guanididum), lysine(amino), histidine (imidazol ring), serine(hydroxyl), threonine(hydroxyl), and aspartic(carboxyl) and glutamic (carboxyl) acids. Each side chain has its own pka values for ionization of the side chains. Note: These amino acids differ in pl values because of the presence of ionizable R chains, but the rest 11 amino acids have almost the same pi (5.5-6). Calculation of pi of amino acids To calculate the pi of these amino acids, we calculate the average pka of the same charge. For example: let s take a negatively charged amino acid ( glutamic acid),take the pka for the carboxyl group which is 2, then add to is pka for the R group (which is 4), and divide them by 2. (2+4)/2=3 In another way : Acidic side chains: The pi will be at a lower ph because the acidic side chain introduces an "extra" negative charge. So, the neutral form exists under more acidic conditions when the extra -ve has been neutralised. For example, for aspartic acid shown below, 7 P a g e

9 the neutral form is dominant between ph 1.88 and 3.65, pi is halfway between these two values, i.e. pi = 1/2 (pka1 + pka3), so pi = Basic side chains: The pi will be at a higher ph because the basic side chain introduces an "extra" positive charge. So, the neutral form exists under more basic conditions when the extra +ve has been neutralised. For example, Histidine,, the neutral form is dominant between ph 6.00 and 9.17, pi is halfway between these two values, i.e. pi = 1/2 (pka2 + pka3), so pi = Note: You have to memorize pka 3, but you can derive pi as viewed previously, or simply memorize them. Sorry for any mistakes. 8 P a g e