Lecture 5-2024 Conversion of AA to Specialized Products PDF

Dr. Sarray Sameh, PhD Overview AA are precursors of many Nitrogen-containing compounds that have important physiologic functions: These molecule include: porphyrins Purines and pyrimidines Hormones Others Nitrogen containing compounds (Creatine, catecholamines, histamine, serotonin…) Creatine Synthe...

Dr. Sarray Sameh, PhD Overview AA are precursors of many Nitrogen-containing compounds that have important physiologic functions: These molecule include: porphyrins Purines and pyrimidines Hormones Others Nitrogen containing compounds (Creatine, catecholamines, histamine, serotonin…) Creatine Synthesis  Site: liver and kidney tissue  AAs: glycine and arginine, and SAdenosyl Methionine (SAM). In muscle: phosphocreatine or creatine phosphate: from reversible phosphorylation of creatine is by creatine kinase using ATP as phosphate donor.  Creatine phosphate is a highenergy compound that provides a small but rapid release of energy in the first few seconds of intense muscular contraction. Creatine degradation  Creatine and phosphocreatine spontaneously cyclize to form creatinine which is excreted in the urine. The amount of phosphocreatine in the body is proportional to the muscle mass The amount of creatinine excreted is proportional to the creatine phosphate content of the body When muscle mass decrease for any reason, the creatinine content of the urine falls In addition, any rise in blood creatinine is a sensitive indicator of kidney malfunction because creatinine is rapidly removed from the blood and excreted Catecholamines (Dopamine, norepinephrine, epinephrine) Catecholamines  Dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline)  Catecholamines are synthesized from tyrosine aa  Tyrosine is obtained from dietary proteins and transported from the blood to the brain and the adrenal medulla:  in the brain : Dopamine and norepinephrine are synthesized and function as neurotransmitters.  in the adrenal medulla: Norepinephrine is also synthesized, as epinephrine (methylated form of norepinephrine) Functions of catecholamines 1) Mediate a variety of the central nervous system functions, such as motor control, emotion, memory processing & endocrine modulation : Dopamine: sends signals throughout the nervous system. It helps regulate the following: movement emotions memory Adrenaline, or epinephrine: responsible for the fight-or-flight response (response to emotional or physical stress). When a person experiences stress, the body releases adrenaline to allow increased blood flow to the muscles, heart, and lungs. Noradrenaline, or norepinephrine: helps the body respond to stress. Noradrenaline release, increases a person’s heart rate and blood pressure. It is also involved in mood regulation and the ability to concentrate. Functions of catecholamines 2) Outside the nervous system: Play a key role in the generation of body heat (thermogenesis); They stimulate consumption of fuels, such as glucose and free fatty acids, thereby generating heat. Stimulate glycogenolysis and the breakdown of triglycerides. Involved in the contraction of smooth muscles o The catecholamines are synthesized from tyrosine. o Tyrosine Hydroxylation: by tyrosine hydroxylase to form 3,4dihydroxyphenylalanine (DOPA) o (rate limiting step) o Decarboxylation of DOPA form dopamine. o Dopamine is hydroxylated by dopamine β-hydroxylase to yield norepinephrine in a reaction that requires ascorbate (vitamin C) and copper. o Epinephrine is formed from norepinephrine by a N-methylation reaction. Parkinson’s Disease  It is a neurodegenerative movement disorder.  Is due to insufficient dopamine production (as a result of the idiopathic loss of dopamine producing cells in the brain)  Administration of L-DOPA (levodopa) is the most common treatment. Degradation of catecholamines o inactivation by oxidative deamination catalyzed by monoamine oxidase (MAO) and by methylation carried out by catechol-O-methyl-transferase (COMT). o The two reactions can occur in either order. o The metabolic products of these reactions are excreted in the urine as vanillylmandelic acid (VMA) from epinephrine and norepinephrine, and homovanillic acid (HVA) from dopamine. Serotonin (5-hydroxytryptamine) o Serotonin has multiple physiologic roles: powerful vasoconstrictor and is involved in modulation of pain perception, regulation of sleep, control of appetite, regulation of body temperature and mood. o 90% of our serotonin supply is found in the digestive tract ( regulation of several physiological functions, such as motility, secretion ) and platelets (enhance platelet aggregation); o Smaller amounts are found in the brain where it functions as a neurotransmittor; serotonin cannot cross the blood brain barrier therefore serotonin that is used inside the brain must be produced within it o Serotonin is synthesized from tryptophan by hydroxylation reaction leading to 5-hydroxytryptophan formation, followed by a decarboxylation and formation of serotonin o Serotonin degradation is carried out by monoamine oxidase (MAO) Histamine A chemical messenger Secreted by mast cells Mediates a wide range of cellular responses (allergic and inflammatory reactions….). It is a powerful vasodilator In the brain, Histamine acts as neurotransmitter Formed by decarboxylation of histidine in a reaction requiring pyridoxal phosphate (PLP) Melanin o Pigment in several tissues (eye, hair, and skin). o Synthesized from tyrosine by pigment-forming cells called as melanocytes. o Functions: protect underlying cells from the harmful effects of sunlight. oA defect in melanin production results in albinism END!