Biosynthesis Lab Report Essay

B) Site of synthesis: 1- In pancreas: Synthesis of taurine in the mammalian pancreas occurs through the cysteine sulfinic acid pathway. First, in this pathway is oxidation of cysteine sulfahydryl group to sulfonic acid, this oxidation is catalyzed by the enzyme cysteine dioxygenase. In turn, cysteine sulfonic acid is decarboxylated to hypotaurine by sulfonoalanine decarboxylase. It is not well known whether hypotaurine is then enzymatically or spontaneously oxidized to taurine.

2- in CNS: Biosynthesis of taurine in CNS occurs via four routes. – Cysteine sulfonic acid (CSA) Decarboxylase route: It is the most accepted route in the CNS. It includes cysteine, CSA, hypotaurine and taurine as a metabolic sequence. 2Cystine dioxygenase route: Cysteine dioxygenase converts cysteine into CSA. In the liver the majority of CSA is oxidized to inorganic sulfate by B sulfinyl pyruvate. 3- The cystic acid decarboxylase route: Light regulates the activity of this enzyme. Brain tissues can decarboxylate cystate. 4- Cystamine deoxygenase route: Mammalian kidney and to lesser extent mammalian heart contain large amount of cystamine deoxygenase enzyme.

This route is insignificant in CNS. Majority of taurine is transported from the circulation into CNS, while neurons only synthesis small amount of taurine. Synthesis of taurine in neuronal cells is a part of an antioxidant mechanism that protects the neuronal cell membrane. Also synthesis of taurine may stabilize the cell membrane and modulate neuronal function. C) Regulation The activity of the enzymes involved, especially the activity of CSAD, is dependent on age and species. Activity of CSAD in human is low and the average taurine daily synthesis ranges from 50 to 125mg.

The key enzyme in taurine synthesis is CDO enzyme. However, for high rates of taurine production by the hepatocytes the activities of CDO and CSD enzymes should be relatively high. Dietary protein regulates mainly the activity of CDO enzyme and cysteine availability. High availability of cysteine favour production of taurine. Availability of dietary sulfur containing amino acid regulates the activity of CDO enzyme which in turn regulates the intracellular levels of taurine. On the other hand, increase intake of dietary proteins decrease the activity of CSAD.

The metabolic fate of cysteine into either cysteine catabolism, taurine synthesis or glutathione synthesis, is dependent mainly on the level of CDO activity. III. Taurine supplementation: In the last few years, the supplemental ingredients for amino acids in various dietary supplements, functional foods and beverages has increased tremendously with highest prevelance being in sports nutrition and “energy” products. Taurine (Tau) is one of the commonest used supplemental amino acid. It is added to foods, beverages and energy drinks.

Products of health food which contain taurine include: the health drink Lipovitan, a taurine containing drink Red Bull which are marketed for athletes to aid their performance. In North America, taurine is marketed for treatment of epilepsy. Several investigations were done to check safety of taurine intake, especially in its conjunction with energy drinks. The European Food Safety Authority (EFSA) have concluded that taurine do not present any safety concerns with the levels currently used in energy drinks. Taurine transport o Transport of taurine occurs via an electrogenic pump (sodium/ taurine transport mechanism).

Cellular transport of taurine is sodium dependant. The ratio of sodium molecules to taurine molecule transported varies in different tissues ranging from 3:1 to 1:1. Transport of taurine in brain require at least 3 Na+ molecules, transport of hypotaurine require 2 Na+ molecules. Transport of taurine takes place in both neurons and glial cells. The transport in glial cells is greater than neurons and astrocytes. Deficiency of taurine stimulates retinal transport of taurine. The sites in mammalian retina where taurine transport is concentrated are, pigment epithelium, photoreceptors and neuronal amoxine cells.

In mammalian retina taurine transport is concentrated in neuronal amoxine cell and photoreceptor and pigment epithelium. It was found that taurine transport fall by 72% if the pigment epithelium was removed from choroid. In human transport of taurine across the pigment epithelia is required for maintaining electrophysiological function of retina. Taurine release There are three ways for cellular release of taurine: The first way is the basal release by leakage of taurine through the cell membrane. The second way is taurine release by reversal of active transport system.

The third way is large efflux when the cell is depolarized. There are evidence that sufficient quantity of endogenous taurine is released with sufficient speed to initiate rapid changes in membrane permeability and potential. Binding of taurine Amino acid can bind to receptor or transport site. Transport site binding is Na+ dependent while binding with receptor is Na+ independent. Interaction of taurine with neurotransmitters:

1. Dopamergic interactions: Dopamine release is increased by taurine. Uptake of dopamine by synaptic vesicles is chlorine dependent. This increase in dopamine uptake occurs secondarily to increase chlorine production by taurine. Taurine not only cause increase dopamine uptake but it also increase synthesis of dopamine. 2. Serotonergic interactions: Taurine increases serotonin by decreasing serotonin turnover in hypothalamus. Also taurine stimulates prolactin secretion via serotonin.

3. Cholinergic interactions: Release of acetylcholine from abdominal ganglion is reduced by taurine. Taurine exert its effect on the presynaptic motor neuron evidenced by the presynaptic coexistence of decarboxylase and acetyl transferase enzymes. Taurine inhibit contraction of gastrocunemeus muscle of frog through postsynaptic non competitive inhibition of carbamylcholine. 4. Interactions with glutamate: Taurine affects glutmate through stimulation of glutamic acid decarboxylase in the brain of epileptic rat where epilepsy is induced genetically. In the granular cerebellar cells of rats taurine has minor effect on glutamate evoked release. Taurine inhibits depolarization induced by glutamate in different system. 5. Interactions with GABA: Taurine hyperpolarizes the cell membrane by mechanism like GABA through increase conductance of Cl-.

So in neuronal ending GABA and taurine have synergic effect, both GABA and taurine antagonize morphine analgesic effect. 6 Interactions of taurine with hormones: Prolactine increases in the circulation by central administration of taurine. Taurine has no effect on leutinizing hormone. Somatostatin and growth hormone release is also stimulated by taurine. Physiological effects of taurine 1- Taurine is an antioxidant: Sulphur containing amino acids naturally protect the cells against extracellular injury caused by oxidative stress.

So, taurine has been investigated for its antioxidant effect in wide variety of diseases as diabetes, myocardial infarction, chronic pancreatitis and oxidative stress induced by ischemia/ reperfusion or oxidative damage induced by drugs. Neutrophil and phagocytes are mainly responsible for microbial killing and production of proinflammatory mediators. These cells have myeloperoxidase enzyme system which play unique role in killing of pathogens which are phagocytosed by neutrophil. Myeloperoxidase system acts via oxidation of chloride to hypochlorous acid (HOCL).

HOCL is a potent microbicidal and potent cellular oxidant. Myeloperoxidase not only oxidize chloride, but also it can oxidize bromide ion to produce hypobromous acid (HOBr). Once activated phagocytes contact with pathogen it produce respiratory burst which cause intense uptake of oxygen. Oxidative process also produces reactive oxygen species (ROS) which have defense mechanism.

Oxidation process starts when membrane associated NADPH reduces molecular oxygen to superoxide and H202 is produced. Myeloperoxidase in neutrophil utilizes H202 to convert Cl- to HOCI or Br- jon to HOBr. Cl- + H202 + H+ HOCI + H2O Br- + H202 + H+ HOBr + H20 Both HOCl and HOBr have an oxidizing effect and can kill pathogens and protect the host cell, so they are considered to be part of innate immunity. Their microbicidal effect is caused by oxidization of cytosolic bacterial methionine residue and oxidation of inner membrane proteins. However, oxidant overproduction and improper neutralization of this oxidant leads to chronic inflammation and oxidative stress development. So antioxidant play critical role in homeostasis and in reduction of hazards of oxidative stress.

The antioxidant acts through (1) reduction of ROS generation, (2) neutralization of ROS and (3) interference with the action of ROS. Taurine concentration is low in plasma and extracellular fluid, while its high intracellulary. Taurine is the major free intracellular amino acid in neutrophil due to high taurine uptake from blood. Taurine play role in innate immunity as it is present with high levels in phagocytes, it also act as cytoprotective and antioxidant through neutralization of HOCL and HOBr acid as it reacts with these acids to form taurine choloramine and taurine bromamine respectively.

These compunds are less toxic and more stable anti-inflammatory mediators. Taurine + HOCI taurine chloramine + H20, Taurine + HOBI taurine bromamine + H20: Also, taurine effectively inhibits ROS production. The expression and activity of antioxidant enzymes such as: superoxide dismutase, catalase and glutathione peroxidase are also enhanced by taurine. 2- Anti inflammatory effect of taurine: In acute inflammatory conditions, thee is massive neutrophil infiltration and production of various inflammatory mediators as: ROS, eicosanoids and cytokines.

Production of proinflammatory cytokines such as: tumor necrosing factor alpha, interleukin 1 and unterleukin 6) is inhibited by taurine. Also taurine chloramine decreases the production of nitric oxide(NO) and prostaglandind E2(PGE2). These effects in addition to the ability of TauCl to induce leukocytes apoptosis, demonstrate the ability of Taucl cto terminate acute inflammatory condition. Also TauCl and TauBr depress the phagocytic cell activity and decrease phagocytic cell oxygen consumption and production of respiratory burst.

TauCl also, increases the expression of peroxyredoxin-1 and thioredoxin-1, which in turn cause decrease in ROS production. TauCl and TauBr significantly increase the expression of heme oxygenase-1 (HO-1) in dose dependent manner. H0-1 has special role in homeostasis as HO-1 decrases the synthesis of priinflammatory heme portion as: cyclocoxygenase (COX-2) and inducible nitric oxide synthase (NOS). Therefore, TauCl and TauBr induce HO-1 in nearby non activated cells and protect these cells against hazards of oxidative stress.