CONVERSION OF AMINO ACIDS TO SPECIALIZED PRODUCTS DR. A. TARAB DEPT. OF BIOCHEMISTRY HKMU

Size: px

Start display at page:

Download "CONVERSION OF AMINO ACIDS TO SPECIALIZED PRODUCTS DR. A. TARAB DEPT. OF BIOCHEMISTRY HKMU"

Melissa McDaniel
5 years ago
Views:

1 CONVERSION OF AMINO ACIDS TO SPECIALIZED PRODUCTS DR. A. TARAB DEPT. OF BIOCHEMISTRY HKMU

2 In addition to serving as building blocks for proteins, amino acids are precursors of many nitrogen-containing compounds that have important physiologic functions These molecules include porphyrins, neurotransmitters, hormones, purines and pyrimidines

3 A. CATECHOLAMINES Dopamine, norepinephrine and epinephrine (adrenalin) are biologically active amines that are collectively termed catecholamines Dopamine and norepinephrine function as neurotransmitters in the brain and in the autonomic nervous system Norepinephrine and epinephrine are also synthesized in the adrenal medulla

4 Functions: Outside the nervous system, norepinephrine and epinephrine act as regulators of carbohydrate and lipid metabolism Norepinephrine and epinephrine are released from storage vesicles in the adrenal medulla in response to fright, exercise, cold and low levels of blood glucose

5 They increase the degradation of glycogen and TAG, as well as increase blood pressure and the output of the heart. These effects are part of coordinated response to prepare the individual for emergencies, and are often called the fight-or-flight reactions

6 Synthesis of catecholamines: - are synthesized from tyrosine Tyrosine is first hydroxylated by tyrosine hydroxylase to form 3,4 dihydroxyphenylalanine (dopa) The enzyme is abundant in the CNS, the sympathetic ganglia and the adrenal medulla and is the rate-limiting step of the pathway

7 Dopa is decarboxylated in a reaction requiring pyridoxal phosphate to form dopamine, which is hydroxylated by the copper containing dopamine-βhydroxylase to yield norepinephrine Epinephrine is formed from norepinephrine by an N-methylation reaction using SAM as the methyl donor

8 Synthesis of catecholamines

9 Degradation of catecholamines: - are inactivated by oxidative deamination catalyzed by monoamine oxidase (MAO) and by O-methylation carried out by catechol-o-methyltransferase (COMT) The aldehyde products of the MAO reaction are oxidized to the corresponding acids

10 The metabolic products of these reactions are excreted in the urine as vanillylmandelic acid, metanephrine and normetanephrine

11 Metabolism of catecholamines neurotransmitters

12 B. CREATINE Creatine phosphate (also called phosphocreatine), is a high energy compound that can reversibly donate a phosphate group to ADP to form ATP Creatine phosphate provides a small but rapidly mobilized reserve of high-energy phosphates that can be used to maintain the intracellular level of ATP during the first few minutes of intense muscular contraction *Note: the amount of creatine phosphate in the body is proportional to the muscle mass

13 1) Synthesis from glycine and the guanidino group of arginine plus a methyl group from SAM Creatine is reversibly phosphorylated to creatine phosphate by creatine kinase, using ATP as a phosphate donor *Note: the presence of creatine kinase in the plasma is indicative of tissue damage, and is used in the diagnosis of myocardial infarction

14 Synthesis of creatine and creatinine

15 2) Degradation creatine and creatine phosphate spontaneously cyclize at a slow, but constant rate, to form creatinine, which is excreted in the urine The amount of creatinine excreted is proportional to the total creatine phosphate content of the body, and thus can be used to estimate muscle mass

16 When muscle mass decreases for any reason (e.g from paralysis or muscular dystrophy), the creatinine content of the urine falls In addition, any rise in blood creatinine is a sensitive indicator of kidney malfunction, because creatinine is normally rapidly removed from the blood and excreted

17 c. HISTAMINE - is a chemical messenger that mediates a wide range of cellular responses, including allergic and inflammatory reactions, gastric acid secretion and possibly neurotransmission in parts of the brain A powerful vasodilator, histamine is formed by decarboxylation of histidine in a reaction requiring pyridoxal phosphate It is secreted by mast cells as a result of allergic reaction or trauma

18 D. Serotonin - also called 5-hydroxytryptamine, is synthesized and stored at several sites in the body By far the largest amount of serotonin is found in cells of the intestinal mucosa Smaller amounts occur in platelets and in the CNS Serotonin is synthesized by hydroxylation of tryptophan

19 The product, 5-hydroxytryptophan, is decarboxylated to serotonin Serotonin has multiple physiologic roles, including pain perception and regulation of sleep, temperature and blood pressure

21 Pathway for serotonin and melatonin synthesis

23 The pineal gland is a pea-sized gland located in the brain The pineal gland secretes the hormone melatonin, which is formed from tryptophan Melatonin seems to be released by the human pineal gland as a response to darkness

24 Therefore, the pineal gland is thought to be involved in establishing daily biorhythms The pineal gland may also play a role in mood disorders and in a variety of aspects of sexual development

25 The biological clock (sleepwake rhythm)

26 E. Melanin - is a water-insoluble polymer of various compounds, derived from tyrosine There are two major forms of melanin: i) eumelanin brown to black in colour ii) pheomelanin yellow to red in colour Functions - occurs in a number of tissues, particularly in the eye, hair and skin

27 In the epidermis, the pigment-forming cells are called melanocytes Melanin is synthesized to protect underlying cells from the harmful effects of sunlight Synthesis of melanin The first step in melanin formation from tyrosine is a hydroxylation to form dopa and dopaquinone catalyzed by the copper-containing enzyme tyrosine hydroxylase (also called tyrosinase)

28 Subsequent reactions leading to the formation of brown and black pigments are also thought to be catalyzed by tyrosinase or to occur spontaneously

32 F. Glutathione Glutathione (GSH) is tripeptide composed of glutamate, cysteine and glycine that has numerous functions within cells GSH serves as a reductant, is conjugated to drugs to make them more water soluble, is involved in amino acid transport across cell membranes (the γ-glutamyl cycle) etc

33 Synthesis of glutathione

34 Structure of G-S-S-G

35 The role of GSH as a reductant is extremely important particularly in the highly oxidizing environment of the erythrocyte Endogenously produced hydrogen peroxide is a toxic substance that, if allowed to accumulate results in the oxidation of haemoglobin to methemoglobin and also causes damage to cell membrane

36 One function of GSH is to remove hydrogen peroxide in the presence of selenium-dependent glutathione peroxidase 2 G-SH + H 2 O 2 G-S-S-G + H 2 O Glutathione reductase utilizes NADPH as a cofactor to reduce G-S-S-G back to two moles of GSH G-S-S-G + NADPH + H + 2 G-SH + NADP +

37 Hence, the PPP is an extremely important pathway of erythrocytes for the continuing production of the NADPH needed by glutathione reductase

Conversionofaminoacidsto specializedproducts

Conversionofaminoacidsto specializedproducts α-nitrogen atom of amino acids is a primary source for many nitrogenous compounds: Heme Purines and pyrimidines Hormones Neurotransmitters Biologically active