The Mighty Twenty Amino Acid Lecture PDF

THE MIGHTY TWENTY Lecture 2B AA Engr ACadiz, MSc 1  Take note!! ❑ In chemical reactions, most often the amino acid will be drawn with the carboxyl group as – COOH and the amine group as NH2. ❑ This is more convenient when dealing with the structure and bondi...

THE MIGHTY TWENTY Lecture 2B AA Engr ACadiz, MSc 1  Take note!! ❑ In chemical reactions, most often the amino acid will be drawn with the carboxyl group as – COOH and the amine group as NH2. ❑ This is more convenient when dealing with the structure and bonding. ❑ However, from time to time it is important to emphasize the appearance of their molecules at pH = 7.4 (physiological pH). ❑ Hence, be aware that the amino acids can be drawn in either form, but the more correct form is as the Zwitterion. Engr ACadiz, MSc 2  1. Glycine (G, Gly) Two main things to remember about Glycine (G) – The  - carbon is NOT a chiral center because it has 2 – H groups attached to it. Therefore, there is no such thing as a D or L form of Glycine (G). – When it appears in proteins, the R – group provides little steric hindrance because of its size. Proteins can bend or rotate easily where Glycine (G) forms part of their structure. Major function – It is a major inhibitory neurotransmitter in the brain. – When released into a neuron it hyperpolarizes the neuron and hence decrease its activity. Can be modified by addition of a fatty acid (myristate – 14 carbons). Engr ACadiz, MSc 3  1. Glycine (G, Gly) Other functions and Benefits – DIGESTIVE SYSTEM SUPPORT – helps regulate bile acid synthesis, which aids in digesting fats. – MUSCLE BUILDING – contributes to muscle development and structural integrity. – DNA AND RNA CONSTRUCTION – crucial for constructing DNA and RNA strands. Food Sources of Glycine – High protein foods like beans, fish, meat, milk and cheese IUPAC Name: 2-Aminoacetic acid Molar Mass: 75.07g/mol (app) MPt: 233 0 C RNA Codons: GGU GGC GGA GGG Engr ACadiz, MSc 4  2. Aspartate (D, Asp) 4. Asparagine (N, Asn) 3. Glutamate (E, Glu) 5. Glutamine (Q, Gln) Glutamate (E, Glu) – is the most important amino acid to learn. Their (Aspartate and Glutamate) R – group contains a carboxylic acid (acidic side chain). At normal pH (pH = 7.4), the carboxyl group carries a negative charge, and are very water soluble (this means that they are commonly found on the surface of proteins) – Aspartate and Glutamate Major function – Glutamate (E, Glu) is a major excitatory neurotransmitter of the brain. It is released by a large number of neurons. It is very important in a region of the brain which influences memory – the hippocampus. Nomenclature – When they have lost their proton from their R – group (as found at physiological pH), they are given the names Glutamate (E) and Aspartate (D). – this signifies the base form. – However, you should be aware that in common usage Glutamic acid (E) and Glutamate (E) are often used interchangeably, as are Aspartic acid (D) and Aspartate (D). Engr ACadiz, MSc 5  2. Aspartate (D, Asp) 4. Asparagine (N, Asn) 3. Glutamate (E, Glu) 5. Glutamine (Q, Gln) An interesting feature of these molecules (Aspartate (D, Asp) and Glutamate (E, Glu)) is that an amide bond can be formed with the carboxylic acid of the R – group. The R groups of these amino acids are more soluble in water, or more hydrophilic, than those of the nonpolar amino acids, because they contain functional groups that form hydrogen bonds with water. Glutamate (E, Glu) can be converted into Glutamine (Q, Gln) and vice versa. Asparagine (N, Asn) can be converted into Aspartate (D, Asp) by hydrolyzing the amide bond and vice versa. The R – groups of both Asparagine (N, Asn) and Glutamine (Q, Gln) are quite polar, having a slightly positive charge. Q END – relationship between the molecules and the sequence. – Glutamine (Q) converted to Glutamate (E) – Asparagine (N) converted to Aspartate (D) Engr ACadiz, MSc 6  Conversion of Glutamic acid or Glutamate to Glutamine. Engr ACadiz, MSc 7  Conversion of Aspartic Acid or Aspartate to Asparagine. Engr ACadiz, MSc 8  2. Aspartate (D, Asp) 4. Asparagine (N, Asn) 3. Glutamate (E, Glu) 5. Glutamine (Q, Gln) DEAMINATION – ketone formation from amino acids. – A very important reaction that some amino acid can undergo in the body is removal of ammonia (NH3 = NH2 and H) from the  - C. – These two (2) groupings are replaced by a ketone (=O). ** – This reaction is a feature of Aspartate (D, Asp) and Glutamate (E, Glu) and is really significant. It is how the body can isolate the carbon chain of amino acids so that it can be used as an energy source. It is how ammonia, which is toxic, is removed. Engr ACadiz, MSc 9  2. Aspartate (D, Asp) 4. Asparagine (N, Asn) 3. Glutamate (E, Glu) 5. Glutamine (Q, Gln) The  - ketoglutaric acid is formed when ammonia is removed from the  - carbon and replaced with a ketone group. – Removing ammonia from Glutamate (E, Glu) and replacing it with a keto group, the carbon skeleton of Glutamate (E, Glu) can be metabolized for energy. – Significance It is a molecule in the tricarboxylic acid cycle (TCA cycle) – energy generating and carbon shuffling cycle in mitochondria. Oxaloacetic acid – is a part of the citric acid cycle, and is where Aspartate (D, Asp) may enter the citric acid cycle – its carbon skeleton used for generating energy. Engr ACadiz, MSc 10  Conversion of glutamic Acid to  - ketoglutaric acid Engr ACadiz, MSc 11  Conversion of Aspartate to Oxaloacetic acid Engr ACadiz, MSc 12  MSG – Monosodium glutamate Engr ACadiz, MSc 13  6. Alanine (A, Ala) This molecule is important in proteins because it has no charge on its R – group. – Its R – group is an acyl group (just carbons and hydrogens not in a ring formation) and all amino acids with acyl groups for their R – groups are uncharged. – Regions of proteins with lots of these types of amino acids are lipid soluble regions of protein. Non-essential amino acid. It is also important as the basis for learning several of the other amino acids. Similar to Glutamate (E, Glu) and Aspartate (D, Asp), NH3 can be removed from the  - C through DEAMINATION. Engr ACadiz, MSc 14  6. Alanine (A, Ala) Additional functions of ALANINE – ENERGY BOOST – acts as an energy courier. It shuttles glucose (simple sugar) around, converting it into usable energy. – MUSCLE SUPPORT – helps protect muscle cells during intense workouts, keeping it safe from damage (ALANINE is produced in the muscle tissue through the breakdown of proteins and transported to the liver, where it is converted back into glucose through GLUCONEOGENESIS). – IMMUNE SYSTEM ALLY – strengthens the immune system ( ALANINE is a precursor for the production of glutathione, a powerful antioxidant, that helps protect cells from oxidative stress. GLUTATHIONE plays a crucial role in the function of immune cells, allowing it to effectively fight off infections and diseases. – REGULATION OF ACID – BASE BALANCE – helping to maintain the pH levels in various tissues and fluids. – SUBSTRATE FOR GLUCOSE – ALANINE CYCLE – helps to maintain blood glucose levels during prolonged exercise or fasting. Engr ACadiz, MSc 15  6. Alanine (A, Ala) Pyruvic acid – is very important in metabolism. – In the LIVER – pyruvic acid can be made into glucose for transport to the muscles. – In MUSCLES – the reverse process can take place – glucose is broken down to pyruvic acid to provide energy without using oxygen. Pyruvic acid can be shuffled into the citric acid cycle so that its carbon skeleton can be used in making new molecules for energy production. Pyruvic acid in high concentration is toxic to the muscles and therefore an AMINE group from Glutamate (E, Glu) can be transferred to Pyruvate to form Alanine (A, Ala). – Alanine (A, Ala) is then transported into the blood back to the liver where it is converted back to pyruvate by removing ammonia. – The pyruvate is then made into glucose (gluconeogenesis) and transported back into the muscles. In this way, the muscles not only remove the acid but also ammonia, both of which are toxic. Engr ACadiz, MSc 16  Conversion of Alanine to Pyruvic Acid Engr ACadiz, MSc 17  7. Phenylalanine (F, Phe) It is an aromatic amino acid. Its symbol “F” is the phonetic sound of “ph”. It is very hydrophobic in proteins. It is an essential amino acid in humans, because of the difficulty to make the ring structure, and hence obtain this amino acid from the diet. L – phenylalanine is the only form of phenylalanine found in proteins. Major dietary sources of L – phenylalanine includes meat, fish, eggs, cheese and milk. Phenylalanine is used for depression, attention deficit – hyperactivity disorder (ADHD), Parkinson’s disease, chronic pain, osteoarthritis, rheumatoid arthritis, alcohol withdrawal symptoms, and a skin disease called VITILIGO. Engr ACadiz, MSc 18  7. Phenylalanine (F, Phe) Engr ACadiz, MSc 19  7. Phenylalanine (F, Phe) PHENYLKETONURIA (PKU) – An inherited disorder that increases the levels of a substance called phenylalanine in the blood. A rare metabolic disorder. – Inability to metabolize phenylalanine because of a lack of the enzyme PHENYLALANINE HYDROXYLASE (PAH) – some people lack phenylalanine hydroxylase and cannot make TYROSINE (Y) – they therefore end up with an excess of phenylalanine which is excreted into the urine after being modified into a KETONE. – PAH is the enzyme responsible for the first step in processing Phenylalanine (F). Engr ACadiz, MSc 20  7. Phenylalanine (F, Phe) If PKU is not treated – phenylalanine can build up to harmful levels in the body, causing INTELLECTUAL DISABILITY and other serious health problems. Signs and symptoms of PKU (vary from mild to severe). – Classic PKU – most severe form. – Infants with classic PKU appear normal until they are a few moths old. – Without treatment – these children develop permanent intellectual disability. – Seizures, delayed development, behavioral problems and psychiatric disorder are also common. – Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body. Treatment of PKU – treated by dietary modification – not eating foods high in phenylalanine, e.g. cheese, eggs, meat, fish, milk. Engr ACadiz, MSc 21  8. Tyrosine (Y, Tyr) Tyrosine (Y) is synthesized from Phenylalanine (F). The enzyme responsible in the synthesis of Tyrosine (Y) from Phenylalanine (F) is Phenylalanine hydroxylase (PAH). – The enzyme works with a molecule called TETRAHYDROBIOPTERIN (BH4) to carry out this chemical reaction. Tyrosine (Y) is used to make several types of hormones (certain chemicals that transmit signals in the brain – neurotransmitters), and a pigment called MELANIN – which gives hair and skin their color. Tyrosine (Y) can also be broken down into smaller molecules that are used to produce energy. Engr ACadiz, MSc 22  8. Tyrosine (Y, Tyr) Conversion of Phenylalanine (F) to Tyrosine (Y). – 2 additional substances are needed – oxygen and a co – enzyme named Tetrahydrobiopterin. – Tetrahydrobiopterin is converted to dihydrobiopterin with a loss of H2. – One oxygen atom is added to the phenyl group of Phenylalanine (F) to form Tyrosine (Y) and one to the H2 to form water. Engr ACadiz, MSc 23  8. Tyrosine (Y, Tyr) Importance of Tyrosine (Y) – In proteins, it is strongly hydrophobic. – The aromatic ring allows Tyrosine (Y) to absorb light at 280 nm (UV light). Since nearly all proteins contain Tyrosine (Y), the amount of light absorbed at 280 nm by a protein is used as an indirect measure of protein concentration. – A precursor for forming a group of neurotransmitters known as CATECHOLAMINES – includes dopamine, noradrenaline, and adrenaline. – In proteins, its R – group can be phosphorylated by forming an ester bond between the hydroxyl group and phosphoric acid. This process changes Tyrosine (Y) from being hydrophobic to hydrophilic (a massive negative charge). This causes the shape of the protein to change as the Tyrosine (Y) tries to leave a hydrophobic region to move towards a more hydrophilic region of the protein – this changes the activity of the protein. Engr ACadiz, MSc 24  8. Tyrosine (Y, Tyr) CATECHOLAMINES – A catechol group is a benzene ring with one or more hydroxyl groups attached. Synthesis of Catecholamines – a multistep process governed by three (3) enzymes. – A hydroxyl group is added to the meta position to the benzene ring of Tyrosine (Y). Engr ACadiz, MSc 25  8. Tyrosine (Y, Tyr) The name, dihydroxyphenylalanine is abbreviated to DOPA, with the O standing for OH. Tyrosine hydroxylase – is the enzyme in the synthesis of Tyrosine (Y) to DOPA and catalyzes the formation of hydroxyl group on Tyrosine (Y) to form DOPA. Engr ACadiz, MSc 26  8. Tyrosine (Y, Tyr) – The next step in the reaction is the conversion of DOPA to Dopamine by decarboxylating DOPA (Note: This reaction, a decarboxylation of the  - Carbon, occurs in some other amino acids to give active biological compounds). Dopamine – the amine form of dihydroxyphenylalanine. Engr ACadiz, MSc 27  8. Tyrosine (Y, Tyr) PHYSIOLOGICAL IMPORTANCE OF DOPAMINE – It is a neurotransmitter in the brain where it has many functions; Important in controlling blood pressure – an increase in Dopamine activity are thought cause of Schizophrenia, Huntington chorea, aggressiveness and repetitive activity such as head swing. Clinically, amphetamines are used to stimulate Dopamine release to control attention deficit disorder – used for social purposes because they quickly create dependence and schizoid behavior. – A hormone that controls the pressure of blood through the kidneys. If blood flow through the kidneys is decreased, Dopamine is released and this causes vasoconstriction of the kidney vessels which increases the pressure of blood flow in the kidneys. Engr ACadiz, MSc 28  8. Tyrosine (Y, Tyr) Dopamine is then converted to Noradrenaline by hydroxylating the β – carbon. Another name for Noradrenaline is Norephinephrine and similarly Adrenaline is called Epinephrine. Engr ACadiz, MSc 29  8. Tyrosine (Y, Tyr) Noradrenaline is an important hormone and neurotransmitter. – It is released as a hormone by the adrenal medulla (principal site of the conversion of the amino acid Tyrosine (Y) into Catecholamines, Epinephrine, Norepinephrine, and Dopamine) as part of the flight and fight response. Adrenal medulla – inner part of the adrenal gland, controls hormones that help a person cope with physical and emotional stress. – It is the main neurotransmitter of the branch of the autonomic nervous system called the SYMPATHETIC NERVOUS SYSTEM. – It plays several role as a neurotransmitter in the brain. Engr ACadiz, MSc 30  8. Tyrosine (Y, Tyr) Noradrenaline is then converted to Adrenaline by adding a methyl group to the amine group of Noradrenaline. Ethanolamine – ethanol with an amine group and phenyl group (Noradrenaline is also a phenylethanolamine). In forming Adrenaline, a methyl group is transferred to the nitrogen. Phenylethanolamine – N – methyl transferase (PNMT) – enzyme that describes the reaction, and the N indicates that the transfer was to the nitrogen group). Engr ACadiz, MSc 31  8. Tyrosine (Y, Tyr) Adrenaline is similar to Noradrenaline in many of its functions. – It is also released as a hormone in the fight or flight response by the adrenal medulla. – It is also a major neurotransmitter in certain regions of the brain. SUMMARY – Tyrosine (Y) formed from the essential amino acid Phenylalanine (F), is the precursor for the biologically active amines like Dopamine, Noradrenaline, and Adrenaline. Engr ACadiz, MSc 32 THANK YOU FOR LISTENING…THERE’S MORE NEXT MEETING Engr ACadiz, MSc 33