Dedication
Page: ii-ii (1)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010002
Taurine: Synthesis, Dietary Sources, Homeostasis, and Cellular Compartmentalization
Page: 1-21 (21)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010003
PDF Price: $30
Abstract
Taurine (β-amino acid ethane sulfonic acid; TAU) is a sulfur-containing
amino acid abundant in the human body. Although TAU does not corporate in the
protein structure, many vital physiological properties have been attributed to this amino
acid. TAU could be synthesized endogenously in hepatocytes or come from nutritional
sources. It has been found that the source of body TAU varies significantly between
different species. For instance, some species, such as foxes and felines, are entirely
dependent on the nutritional sources of TAU. On the other hand, TAU is readily
synthesized in the liver of animals such as rats and dogs. The TAU synthesis capability
of the human liver is negligible, and we receive this amino acid from food sources. The
distribution of TAU also greatly varies between various tissues. Skeletal muscle and
the heart tissue contain a very high concentration of TAU. At subcellular levels,
mitochondria are the primary targets for TAU compartmentalization. It has been found
that TUA also entered the nucleus and endoplasmic reticulum. The current chapter
discusses the synthetic process and dietary sources of TAU. Then, the transition of
TAU to sub-cellular compartments will be addressed. Finally, the importance of TAU
homeostasis in the pathogenesis of human disease is mentioned.
Taurine and the Mitochondrion
Page: 22-44 (23)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010004
PDF Price: $30
Abstract
Several studies have evaluated the subcellular compartmentalization of
taurine (TAU) and its cellular and molecular mechanisms of action. Meanwhile, it has
been found that TAU is largely uptaken by mitochondria. TAU could improve
mitochondrial function by incorporating it into the basic mitochondrial structures and
protein synthesis (e.g., mainly mitochondrial electron transport chain components).
Several other mechanisms, including the enhancement of mitochondrial calcium
sequestration, regulation of mitochondria-mediated reactive oxygen species (ROS)
formation, prevention of mitochondria-mediated cell death, and mitochondrial pH
buffering, are also involved in the mitochondrial function regulatory properties of
TAU. Therefore, TAU has been used against a wide range of pathologies, including
mitochondrial injury. In the current chapter, a review of the approved molecular
mechanism for the effects of TAU on mitochondria is provided. Then, the applications
of TAU on a wide range of complications linked with mitochondrial impairment are
discussed. The data collected here could give a better insight into the application of
TAU as a therapeutic agent against a wide range of human diseases.
Applications of Taurine in the Central Nervous System Disorders Linked with Mitochondrial Impairment
Page: 45-75 (31)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010005
PDF Price: $30
Abstract
Taurine (TAU) reaches a high concentration in the central nervous system
(CNS). The physiological role of TAU in the CNS is the subject of many
investigations. It has been suggested that this amino acid could act as a membrane
stabilizer, a modulator of calcium signaling, a trophic factor for neuronal development,
and even be proposed as a neurotransmitter in the CNS. Besides, several investigations
revealed the neuroprotective properties of TAU in various experimental models.
Multiple mechanisms, including the inhibition of the excitotoxic response, the blockade
of cytoplasmic calcium overload, regulation of oxidative stress, and the positive effects
of TAU on mitochondrial parameters, have been proposed for the neuroprotective
properties of this amino acid. Today, it is well-known that mitochondrial function and
energy metabolism play a pivotal role in the pathogenesis of various neurodegenerative
disorders and xenobiotics-induced neurotoxicity. Hence, targeting mitochondria with
safe and clinically applicable agents is a viable therapeutic option in various
neurodegenerative disorders. In the current chapter, the effects of TAU on the CNS will
be highlighted, focusing on the positive effects of this amino acid on mitochondrial
parameters. The data could help the development of safe therapeutic agents against
CNS complications.
Taurine and the Cardiovascular System: Focus on Mitochondrial-related Pathologies
Page: 76-107 (32)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010006
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Abstract
It is well-known that taurine (TAU) concentration in the excitable tissues,
such as the myocardium is exceptionally high (up to 30 mM). TAU accumulation in the
cardiomyocytes is a transporter-mediated process. Therefore, this amino acid should
play a critical role in cardiac tissue. Several studies revealed that a decrease in cardiac
TAU could lead to atrophic cardiomyopathy and impaired cardiac function. At
subcellular levels, the effects of TAU on mitochondria and energy metabolism are an
essential part of its function in the heart. Besides, it has been found that exogenous
TAU supplementation significantly enhanced cardiac mitochondrial function and ATP
levels. In the current chapter, the effects of TAU on cardiovascular diseases linked with
mitochondrial impairment are highlighted, and the role of TAU as a cardioprotective
agent is discussed. The data collected here could provide clues in managing a wide
range of cardiovascular complications connected with the energy crisis and
mitochondrial dysfunction.
Taurine and the Liver: A Focus on Mitochondria-related Liver Disease
Page: 108-136 (29)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010007
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Abstract
Although the liver is the leading site for taurine (TAU) synthesis, the level
of this amino acid in hepatic tissue is relatively low. It is well-known that TAU is
efficiently redistributed from hepatocytes to the circulation. However, the human
body’s capacity for TAU synthesis is negligible, and we receive a very high percentage
of our body TAU from exogenous sources. Plasma TAU is taken up by several tissues,
such as the skeletal muscle and the heart. The roles of TAU in liver function are the
subject of many investigations. It has been found that TAU could have beneficial
effects against xenobiotics-induced liver injury, alcoholism-associated hepatic damage,
non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), or
even viral hepatitis infections. The inhibition of cytochrome P450, alleviation of
oxidative stress, inhibition of inflammatory reactions, and the mitigation of tissue
fibrosis are fundamental mechanisms proposed for the hepatoprotective properties of
TAU. On the other hand, many studies indicate that hepatocytes’ mitochondria are
essential targets for the cytoprotective properties of TAU. The current chapter reviews
the beneficial role of TAU on the most common liver disorders, focusing on the effects
of this amino acid on mitochondrial function and energy metabolism.
Taurine as an Anti-aging Compound: Focus on Mitochondria-related Mechanisms
Page: 137-173 (37)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010008
PDF Price: $30
Abstract
It has been well-established that mitochondria play a crucial role in aging.
Thus, targeting mitochondria is a leading approach for anti-aging pharmacological
interventions. On the other hand, the anti-aging effect of taurine (TAU) is an exciting
feature of this amino acid. Effects of TAU on mitochondria-facilitated oxidative stress
as well as mitochondria-mediated cell death, seem to play a pivotal role in its antiaging
properties. The current chapter will discuss a good body of investigations that have
converged at a consensus regarding mitochondria (dynamics and functionality) and
oxidative stress as essential mechanisms involved in the aging process. In each part, the
potential antiaging properties of TAU and its mechanisms of action are also
highlighted. Finally, in the last section of this chapter, we described the possible role of
recently-discovered signaling pathways (i.e., aryl hydrocarbon receptors; AhR) on
mitochondria and their relevance to senescence.
Taurine and Skeletal Muscle Disorders: Highlighting the Mitochondria-dependent Mechanisms
Page: 174-199 (26)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010009
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Abstract
Skeletal muscle tissue contains a massive taurine (TAU) in millimolar
concentrations. Several studies mentioned the importance of TAU in normal skeletal
muscle function. It has been found that this amino acid plays a wide range of functions,
ranging from osmoregulatory properties to the regulation of cytoplasmic Ca2+
homeostasis. Recent findings mentioned that TAU deficiency in the skeletal muscle
leads to decreased exercise capacity, severe weakness, and muscle waste. On the other
hand, it has been repeatedly shown that TAU supplementation could increase skeletal
muscle performance in many disorders. These data mention the essential role of TAU
in the skeletal muscle. Interestingly, it has been found that the effect of TAU on
cellular mitochondria is an important feature of this amino acid in skeletal muscles.
The current chapter highlights the physiological roles of TAU in muscle and its
importance in the pathophysiology of skeletal muscle disorders. Then, the essential role
of TAU in cellular mitochondria and its importance in muscle function is described.
And the relevance of this amino acid in managing skeletal muscle pathologies is
discussed.
Taurine and the Renal System: Effects on Mitochondrial Function and Energy Metabolism
Page: 200-225 (26)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010010
PDF Price: $30
Abstract
Renal tissue is the main organ responsible for regulating the human taurine
(TAU) pools. A large amount of intact (un-metabolized) TAU is excreted through the
urine daily. On the other hand, it has been found that TAU plays a fundamental role in
renal function. Several physiological roles, including regulating the blood flow, acting
as an osmolyte, and controlling ions transport, are attributed to TAU in the kidneys.
Besides, many investigations revealed that TAU could provide several pharmacological
roles in renal disorders. It has been found that the antioxidant properties of TAU, its
effects on processes such as the renin-angiotensin system, nitric oxide synthesis, and,
most importantly, the regulation of mitochondrial function in the kidney could play a
fundamental role in the pharmacological effects of this amino acid in the kidney. The
current chapter provides a brief review of TAU's fundamental role in renal function.
Then, the beneficial effects of TAU administration in renal disease are highlighted,
focusing on the impact of this compound on mitochondria-related mechanisms. The
data collected in this chapter might shed light on the potential clinical application of
TAU as a safe drug candidate against a wide range of renal diseases.
The Mechanism of Action of Taurine in the Digestive System
Page: 226-238 (13)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010011
PDF Price: $30
Abstract
Several transporters have been identified for taurine (TAU) absorption from the gastrointestinal (GI) tract. The Na+/Cl--dependent taurine transporter (TauT) and PAT1 (SLC36A1) are well-known TAU transporters in the GI. These transporters efficiently deliver TAU from GI to the bloodstream. On the other hand, no metabolic pathway has been identified for TAU in the human body. But, it has been found that GI-resident bacteria are able to metabolize TAU to sulfur-containing chemicals (e.g., H2S). Hence, GI is the primary place for TAU metabolism. TAU-conjugated compounds such as bile acids are also excreted through GI. Compounds such as H2S could be re-absorbed from GI and have a tremendous physiological effect on other organs (e.g., heart and vessels). Finally, it should be noted that several studies mentioned that TAU could protect GI in various pathological conditions (e.g., xenobiotics-induced GI damage). In the current chapter, a brief review of the absorption, metabolism, and excretion of TAU is provided. Then, the importance of TAU metabolites in the GI and other organs is highlighted. Finally, the effects of TAU on GI complications are discussed, focusing on the effects of this amino acid on oxidative stress biomarkers and mitochondrial impairment. These data could give a new concept of the physiological roles of TAU as well as its effects on GI complications.
The Role of Taurine in the Reproductive System: A Focus on Mitochondria-related Mechanisms
Page: 239-273 (35)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010012
PDF Price: $30
Abstract
The cytoprotective features of taurine (TAU), including anti-programmed cell death, membrane stabilization, antioxidant, anti-inflammation, osmoregulation, and intracellular calcium homeostasis regulation, have been well addressed in the literature. TAU has also been considered a potent agent for diminishing various xenobioticscaused by physiological and pathophysiological alterations through its antioxidant action in reproductive and non-reproductive organs. Hence, exogenous TAU administration is the topic of many in-depth investigations. Several studies revealed that the antioxidative effect, anti-cellular death, and anti-inflammatory effects of TAU are involved in inhibiting xenobiotics-induced reproductive toxicity. Hence, the exact targets of TAU during the intracellular routes related to mitochondrial functionality (such as mitochondria-mediated oxidative stress and cell death) triggered by xenobiotics are discussed in this chapter. The data collected in this chapter suggest that TAU could be highly protective against various kinds of xenobiotics-induced gonadotoxicity, spermatotoxicity, and steroidogenotoxicity (hormonal steroids’ genotoxicity) via its antioxidative, anti-inflammatory, and anti-cell death features. Furthermore, this amino acid also acts as an anti-apoptotic and anti-autophagic molecule by modifying the regulation of some related genes and proteins and inflammatory and mitochondrial-dependent signaling molecules.
Role of Taurine Supplementation in Obesity: Stimulating Fats to Burn in Cellular Power Plants
Page: 274-307 (34)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010013
PDF Price: $30
Abstract
With changes in lifestyle and eating habits, obesity is a significant health issue, especially in developed countries. Obesity could be induced by an imbalance between energy expenditure and energy intake. Obesity harms several body organs’ functions by causing impairments in vital intracellular organelles such as mitochondria. Meanwhile, it has been found that chronic inflammation and oxidative stress could induce mitochondrial impairment in various tissues of obese individuals. On the other hand, it has been revealed that there is a negative correlation between obesity and taurine (TAU) biosynthesis. In the current chapter, we tried to present a good body of evidence on the role of mitochondria in various types of fatty tissues, including white adipose tissues (WAT), brown adipose tissues (BAT), and beige/brite/inducible/brownlike adipose tissues (bAT). We also highlighted the effects of TAU on mitochondria related signaling in adipocytes. The data collected in this chapter could help develop new strategies for preventing and treating obesity and its associated complications.
The Importance of Appropriate Taurine Formulations to Target Mitochondria
Page: 308-327 (20)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010014
PDF Price: $30
Abstract
As repeatedly mentioned in the current book, taurine (TAU) is a very
hydrophilic molecule. Hence, the passage of this amino acid through the physiological
barriers (e.g., blood-brain barrier; BBB) is weak. In this context, experimental and
clinical studies that mentioned the positive effects of TAU on CNS disorders
administered a high dose of this amino acid (e.g., 12 g/day). For example, in an animal
model of hepatic encephalopathy, we administered 1 g/kg of TAU to hyperammonemic
rats to preserve their brain energy status and normalize their locomotor activity. In
some cases, where anticonvulsant effects of TAU were evaluated; also, and a high dose
of this amino acid was used (150 mg/kg). In other circumstances, such as investigations
on the reproductive system, the blood-testis barrier (BTB) could act as an obstacle to
the bioavailability of TAU. On the other hand, recent studies mentioned the importance
of targeted delivery of molecules to organelles such as mitochondria. These data
mention the importance of appropriate formulations of this amino acid to target brain
tissue as well as cellular mitochondria. Perhaps, TAU failed to show significant and
optimum therapeutic effects against human disease (e.g., neurological disorders)
because of its inappropriate drug delivery system. Therefore, targeting tissues such as
the brain with appropriate TAU-containing formulations is critical. The current chapter
discusses possible formulations for bypassing physiological barriers (e.g., blood-brain
barrier; BBB or BTB) and effectively targeting subcellular compartments with TAU.
These data could help develop effective formulations for managing human diseases
(e.g., CNS disorders or infertility issues in men).
Subject Index
Page: 328-332 (5)
Author: Reza Heidari and M. Mehdi Ommati
DOI: 10.2174/9789815124484123010015
Introduction
Taurine, or 2-aminoethanesulfonic acid, is one of the most abundant sulfur-containing amino acids in the human body. It is found in the heart, brain, retina, and skeletal muscles, and is synthesized in the pancreas. Studies have revealed that taurine is of high physiological importance: it protects against pathologies associated with mitochondrial diseases, and linked processes like aging, metabolic syndrome, cancer, cardiovascular diseases, and neurological disorders. It is also used as a nutritional supplement. Taurine and the Mitochondrion: Applications in the Pharmacotherapy of Human Diseases explores the significance of taurine in the biology of mitochondria. It also explains its role as a pharmacological agent for treating different diseases. Readers will gain an insight into the crucial role it plays in human physiology and the benefits of taurine supplements. Topics covered in this reference include - Synthesis of taurine and its dietary sources - The Role of taurine in mitochondrial health - Taurine as a neurotransmitter - Beneficial effects of taurine in physiological systems such as the reproductive system, renal system, and the gastrointestinal tract - Hepatoprotective and anti-inflammatory properties of taurine - The anti-aging promise of taurine supplementation - Role of taurine supplementation in obesity