Taurine

Thyroid Factor

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I he ampholytic amino acid taurine (2-aminoethane sulfonic acid molecular weight 125) is a conditionally essential nutrient.

Abbreviation

TAUT taurine transporter (SLC6A6)

Nutritional summary

Function: Critical for kidney function and protection of cells against dehydration, eye and brain function, hormonal regulation, nutrient absorption (bile) and protection against oxygen free radicals (hypotaurine)

Requirements: In most people endogenous synthesis is adequate (dependent on cystein, niacin, vitamin B6. iron, and molybdenum). Prematurely born infants and possibly even healthy young infants may depend partially on dietary intake: a newborn's requirement

Figure 8.91 Taurine from endogenous and dietary sources combined is in excess of6mg/day. Adults may-

need as little as 30 40mg.d from endogenous synthesis and diet combined.

Food sources: Clams, fish, and meat are the best sources, human milk is a good source for infants. Taurine is absent from a lacto-ovo-vegetarian or vegan diet.

Deficiency: A lack of taurine in young infants may cause irreversible degeneration of the retina, limit brain maturation, and slow growth and weight gain.

Excessive intake: The risks from very high taurine intakes (>l 2 g day tare not known.

Endogenous sources

Taurine is produced endogenously, mainly in liver cvtosol: its synthesis requires cysteine, niacin, iron, pyridoxine. and molybdenum.

In the main metabolic pathway cysteine is oxidized to 3-sulfinoalanine, The cysteine dioxygenase (EC1,13.11.20) responsible for this reaction uses iron and NAD or NADP as prosthetic groups. Sulfuioalanine decarboxylase (EC'4.1.1.29) with pyri-doxal phosphate as a prosthetic group generates hypotaurine, which is finally converted into taurine by hypotaurine dehydrogenase (ECI.K.I .3) in an NAD-dependent reaction Hypotaurine dehydrogenase contains both heme and molybdenum cofactor (molybdoptcrin. a pterine with molybdenum coordinated to it).

Another pathway in the cytosol of most tissues uses cysteamine for hypotaurine and taurine synthesis; this reaction is catalyzed by cysteamine dioxygenase (EC 1,13.11.19), a metalloprotein that contains one atom each of copper, zinc, and ferric iron.

Dietary sources

Most of the body's taurine comes from meat (200-400mg/kg), fish (300-700mgkg), clams (1500-2400 mg. kg), milk (bmgl). and a few other foods of animal origin; it is not a component of plant foods. Typical intakes in Chinese omtuvores were 30-80 nig/d (Zhao et id.. 199X). Human milk provides 40mg I. colostrum is an even richer source.

Digestion and absorption

Significant amounts of taurine (more than 20(H) mg,d) are secreted with bile as conjugates with bile acids; these conjugates are cleaved by bacterial chenodeoxy-choloyltaurine hydrolase l EC'3.5.1.741. Free taurine is taken up from the small intestinal (ileal) lumen by a sodium chloride-dependent cot ran sport cr. flic (¡ABA transporter I is expressed in small intestine (Jin et id.. 20011 and might be solely or in part responsible for this transport activity.

Taurine is transported out of the enteroeytvs by the NaCl-dependent taurine transporter (TAUT; SLC6A6).

Transport and cellular uptake

Blood circulation. Uptake of taurine into cells is mediated by a sodium/taurine (»transporter that is osmoticaily induced and upregulated by protein kinase C (PK.C)

COOH I

HJM-CH I

SH Cysteine

COOH I

Cysleinesulfinate

Suilinoaiamne decarboxylase (PLP)

Suilinoaiamne decarboxylase (PLP)

Hypo taurine

Cysleamine

Cysleamine dioxygenase (Cu. Zn. Fe3')

Hypo taurine dehydrogenase (molybdopterin cofactor ■ heme)

H20+ NAD

V^NADH

SO., Taurine

Figure 8.92 Endogenous taurine synthesis

(Stevens et at., 1999). Hypotaurine, but not taurine is transported by the NaC'l-depcndent GAT-2 transporter in liver cells (Liu et a/., 1999).

Materno-fetal transfer: The same taurine transporter has also been found in placenta, brain, and kidney, it is not clear how taurine is exported from the syntrophoblast into the intercapillary space on the fetal side of the placental membrane. Blood-brain bamer. GAT2/BGT-1 contributes to the transport of taurine from blood circulation into brain (Takanaga ei a!.. 2001). The NaC!-dependent taurine transporter TAUT is also involved. The entire sequence of events contributing to crossing the

blood brain barrier remains to be resolved. Some taurine is also transported in the reverse direction (Kang, 2000).

Metabolism

Taurine breakdown uses the reactions of synthesis in reverse, mainly in the lt\er. Hypotaurine dehydrogenase (ECl.8.1.3) contains molydopterist and heme, reduces taurine again to hypotaurine, which can be converted into cysteine sullinate (sulfino-alanine) by sulfinoalanine decarboxylase (EC4.I.1.29. PLP-dependent). At this point taurine breakdown joins the pathway lor cysteine catabolism. The abundant cytOsolie aspartate aminotransferase (PLP-depcndent: EC2.6.1.1) generates beta-sui liny [pyruvate, which decomposes spontaneously into sulfite and pyruvate. Alternatively, aspartate 4-decarboxylase (EC4.1.1.12) can cleave cystcinesulfinate into sullitc and alanine I Pat hod and Fellman, 19K5). Finally, the molybdenum-containing sulfite oxidase (ECl .8.3.1) oxidizes sulfite oxidation to sulfate with cytochrome c as the electron acceptor. Taurine metabolism is thus intimately dependent on molybdenum, since two key-reactions use molybdenum cofactor (molybdopterin).

Storage

Muscle cells contain most of the body's taurine; smaller amounts are m liver and other tissues, and as bile acidtaurine conjugates (1%) in liver and intestinal lumen. Glu-taurine (y-L-glutamy [taurine) may be an intracellular storage form.

Excretion

Normally about 2- 3% of excreted bile acid* is lost with fcces and the attached taurine with them. Daily taurine losses may be estimated at ftOmg assuming total bile acid losses of SOOmg, about half ofwhich will be conjugated with taurine.

The taurine transporter (TAUT, SLC6A6) cotransports taurine with two sodium and one chloride ion into endothelial cells of the proximal renal tubule (Chesney el ai, 1990; Qitoun a at,, 2001). TAUT also mediates transport across the basolateral membrane. Hypotaurine can be transported in kidney cells by the NaCl-dependent G AT-2 transporter iLiu vi ul.. 1999). but the quantitative sigmlicance of this pathway is unknown.

Taurine

Hypolaurine dehydrogenase {molybdenum coiactor * heme)

CHj I

Hypota urine

Sulfinoaianine decarboxylase (PLP)

COOH I

CHj I

Cysleinesullinate

Aspartate ammo-transterase (PLP)

«-keto-giu rarate glutamate

COOH I

SO^H It-Sullinylpyruvate

Sulfile oxidase (molybdenum cefaclor)

(nonenzymalic)

Sulfile oxidase (molybdenum cefaclor)

Pyruvate

Figur« 8.94 Taurine metabolism

Regulation

At high taurine intakes capacity for the taurine transport system is exceeded and most taurine is excreted unchanged with urine (Wang and Zhao, 1998). Regulation ofTAUT expression in straight proximal tubule cells and thereby modulation of taurine recovery (Matsell el at, 1997) also seems to he an important mechanism for the maintenance ofa stable body pool. The expression ofTAUT is down regulated when protein kinase C-mediated signaling is activated (Han et al., 1999).

H,N Function

CH, Osmolar buffering: Taurine is ihc most abundant intracellular iree amino acid and a potent ampholyte. This allows it to stabilize intracellular pH and protect against water loss to extracellular environment with high osmotic pressure. Such protection is of

12 S03

particular importance in the kidney where the osmolarity is more than two-fold higher rigun- 8.9S towards the tip of the loop of Henle than in other regions. Without the ability to with-

Taunn* is an ampholyte stand such high osmotic pressure the countercurrent amplification of sodium chloride and water transport from primary filtrate back into circulation would not be possible. The great importance of taurine for kidney function is underscored by the fact that the highcsl expression of a key enzyme of taurine synthesis. suKinoalanine decarboxylase (EC4.1.1.29), occurs in proximal straight tubules of the kidney (Reymond et al., 2000). Taurine may also increase expression of the osmolarity sensor protein ENVZ (Moenkemann et al., 194'J), which modulates water and electrolyte transport by altering aquaporin expression.

In response to low osmolarity. taurine can exit brain cells such as astrocytes through specific channels formed by phospholemman. Such lluxes of taurine, which contribute to regulatory volume decrease of the cells, are modulated by protein kinase A (Moran et at,, 2001).

Bile acid conjugation: Coenzyme A-conjugated bile acids can be conjugated to taurine through the action of glycine N-choloy¡transferase (EC2.3.1.65). The enzyme links nearly 50% of bile acids with taurine.

Glutaurine: The dipeptide from taurine and glutamate is called glutaurine. It has been reported to participate in neuroexcitation (Wu et al., 1992) and lo have antiamnesic potential when given orally (Balazs et at., 1088). Glutaurine may also be involved in the regulation of thyroid and parathyroid activity I Baskin et at., 1987).

Ant/oxidation Hypotaurine acts as an antioxidant (Shi et al., 1997; Devamanoharane/a/., 1907), particularly by converting the oxidant hvpochlorousacid intotaurochloramine. Macrophages generate hypoehlorous acid during antibacterial action (free radical burst) and phagocytosis.

References

Balazs M. Telegdy G. Effects of glutaurine treatment on electroshoek-induced amnesia.

Antiamnesic action of glutaurine. Neuropeptides I988;12:55 8 Buskin S. Bartuska D. fhampi N, McBride M, f innigan J. The effect of glutaurine on thyroid hormones in the rat. Neuropeptides 1987:9:45 50 Bitoun M, Le\ illain O, fappaz M. Gene expression of the taurine transporter and taurine biosynthetic enzymes in rat kidney after amidiuresis. PtI trch Eur J Physiol 20(11:442:87 95

Chesney RW. /eliko\ ic 1. Jones DP. Budreau A. Jolly k. The renal transport of taurine and the regulation of renal sodium-chloride-dependent transporter activity. Pediatr Nephrol 1990:4:399 407 Devamanoharan PS. Ali AH, Varma SD. Prevention of lens protein glyeation by taurine. MoI Cell Biochetn 1997:177:245 50

Han X, Budreau AM. Chesney RW. Ser-322 is a critical sue for PRC regulation of the

MDCK cell taurine transporter (pNCT). J Am Soc Nephrit 1999:10:1874- 9 Jin XP. Huang F, Yang N. Lu BF, Fei J. Guo LH. GABA transporter t transcriptional starting site exhibiting tissue specific difference. Ceti Res 2001 ;l 1:161 3 Rang YS. taurine transport mechanism through the blood brain harrier in spontaneously hypertensive rats. Adv Exp Med Biol 2000:483321 4 Liu M. Russell RL, Be ¡gel man L, Handschumacher RL, Pi/zorno G, beta-alariine and alpha-lluoro-beta-alanine concent rat ive transport in rat hepatocytes is mediated by GABA transporter GAT-2. Am J Physiol 1999:276:0206 G210 Matsell DG, Bennett T. Han XB. Budreau AM, Chesney RW Regulation of the taurine transporter gene in the S3 segment of the proximal tubule. Kidney hit I997;52: 748-54

Moenkcmann H, Lahudova O, Ycghiazarian K. Rink H. HoegerH, Lubcc G. Evidence that taurine modulates osmoregulation by modification of osmolality sensor protein EN VZ-expression. Amino Acids 1999; 17:347-55 Motrin J. Morales-Mulia M. Pasantes-Moraies H Reduction of phospholemman expression decreases osmosensitive taurine efflux in astrocytes. Biochim Biophys Acta 2001;1538:313-20

Rathod PK. Feltman JH. Identification of mammalian aspartate-4-decarboxylase, .-irt'/i

Biochem Biophys 1985;238:435-46 Reymond I. Bitoun M. Levi I lain 0, lappa/ M. Regional expression and histological localization of cysteine sullinate decarboxylase tnRNA in the rat kidney. J Histochem Cytochem 2000;48:I46I 8 Slit X. Flynn DC*. Porter DW, Leonard SS. Vallyalhan V Castranova V. F.flicacy of taurine based compounds as hydroxy! radical scavengers in silica induced peroxidation. Ann Clin Lab Sci 1997:27:365 74 Stevens MJ. HosakaY, Masterson JA, Jones SM. Thomas TP. Larkin DD. Downregulation of the human taurine transporter by glucose in cultured retinal pigment epithelial cells. Am J Physiol 1999;277:E760 71 fakanaga 11. Ohtsuki S. Hosoya K, Terasaki T. GAT2/BGT-1 as a system responsible for the transport Ofgamma-aminobutyrie acid at the mouse blood-brain barrier../Cervb Blood Flow Meted) 2001:21:1232 9 Wang XB. Zhao XH. The effect of dietary sulfur-containing amino acids on calcium excretion. Adv Exp Med Biol 1498:442:495 -9 Wu J V. Tang XW.Tsai WH Taurine receptor: kinetic analysis and pharmacological studies. Adv Exp Med Biol 1992;315:263-8 Zhao X. Jia J. Lin Y, Taurine content in Chinese food and daily intake of Chinese men.

Adv Exp Med Biol 1998:442:501-5 OH

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