A Seminar on Taurine Deficiency in Cats Group 10 March 3, 2014

Biochemistry of Taurine Figure 1. Chemical structure of taurine IUPAC name : 2-aminoethanesulfonic acid Taurine is an sulfonic acid containing an amino group, yet it is not an amino acid as it is often called one, because it lacks a carboxyl group.

Biosynthesis of Taurine Methionine Vit Transulfuration Cysteamine Phosphopantothenate Cystein Cysteamine dioxygenase Cysteine dioxygenase (CDO) Hypotaurine Cysteine sulfunic acid Cysteine sulfinate decarboxylase Cysteine sulfinic acid pathway Hypotaurine decarboxylase Cysteine sulfinic acid dehydrogenase Taurine Cysteine sulfinate decarboxylase Cysteic acid A dietary deficiency of vitamin B6 shows a depressing effect on taurine biosynthesis.

Taurine Transport in the Body Taurine transport across cell membrane Na+ - dependent taurine transporter Taurine release from the cell via three mechanisms Exocytosis occurs at basal membrane Energy-dependent transporter Ca2+ - dependent transport

Physiological Function of Taurine system Visual system Immune system Renal system Bile acid conjugation Nervous system Cardiovascular

Roles of Taurine in Nervous System Taurine acts as a neurotransmitter. - Its ability to elicit neuronal hyperpolarization. - The presence of specific taurine synthesizing enzymes (CSAD), taurine-specific receptor, and a taurine transporter system. Taurine is essential for normal function of central nervous system. Its accumulation varies in location, depends on species and age. Its amount gradually decreases after development. Taurine can be found in majority of brain cells, more concentrated in glial cells than neurons. Astrocytes can accumulate taurine up to 20 mM. CSAD = Cysteine sulfinic acid decarboxylase

Taurine as a neuroprotective agent. - Cellular injury prevention - Intracellular calcium-ion modulation - Change of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax) ratio - Autolysis inhibition Taurine as a neuroprotective agent.

Roles of Taurine in Cardiovascular System Taurine acts as positive inotropes by promoting calcium-ion release from sarcoplasmic reticulum in cardiac myocytes by modulates calcium transportation during the excitation- contraction coupling.

Roles of Taurine in Cardiovascular System Excitation-contraction coupling of cardiac myocyte.

Roles of Taurine in Visual System Taurine is found in high concentration at the retina, particularly in photoreceptor cell bodies of outer nuclear layer. Kittens are more prone to taurine depletion in photoreceptor cells compared to adult cats.

Photoreceptor cell Phototransduction system outer segment Inner segment Synaptic terminal Photoreceptor cell Phototransduction system

taurine depolarization Intracellular Ca2+ Outer segment Na+ Ca2+ Ca2+ exchanger CNG channel disks Na+ Ca2+ Ca2+ Ca2+ Na+ Na+ reopening depolarization taurine Intracellular Ca2+

Roles of Taurine in Immune System Myeloperoxidase Taurine can eradicate free radicals generated from specific myeloperoxidase reaction, i.e. hypochlorous acid (HOCl) and hypobromous acid (HOBr), thus it can reduce oxidative stress. Myeloperoxidase enzyme presents in leucocytes as a defense against microbes can generate free radicals which are potentially toxic to host cells.

Roles of Taurine in Renal System Renal vascular resistance Taurine aids in renal blood flow regulation. Glomerulus Elimination of reactive oxygen species (ROS) Proximal tubule Taurine affects sodium transportation. Regulation of taurine body pool size. Medullary collecting duct Taurine acts as osmoregulator, thus it can control the cell volume. Taurine may prevent glomerulonephritis, diabetic nephopathy, chronic renal failure, and acute kidney injury (AKI)

Taurine transport in renal tubular cell Roles of Taurine in Renal System Taurine transport in renal tubular cell

Taurine Deficiency in Cats -Bile conjugation -CSAD Why are cats more likely to develop taurine deficiency? How does taurine deficiency affects cats health? Cats have low activity of cysteine sulfinic acid decarboxylase (CSAD) in the liver, which is essential for taurine biosynthesis. It is obligatory that cats conjugate bile acid solely with taurine, even in the status of taurine depletion.

Taurochenodeoxycholic acid Bile acid conjugation Cholesterol 7αHydroxylase 7αHydroxyCholesterol Cholic acid (primary bile acid) Chenodeoxy (primary bile acid) Glycine Taurine Taurine Cats have low activity of cysteine sulfinic acid decarboxylase (CSAD) in the liver, which is essential for taurine biosynthesis. It is obligatory that cats conjugate bile acid solely with taurine, even in the status of taurine depletion. Taurochenodeoxycholic acid Glyconolic acid Taurocholic acid Linthocolic acid (secondary bile acid)

Taurine Deficiency on Cats Health Cardiac Function Visual System Immune System Reproductive System & Development

Impaired sensitivity of contractile protein to Ca2+ Cardiac Function Impaired sensitivity of contractile protein to Ca2+ Decrease Ca2+ influx Cell Apoptosis Impaired systole and diastole Feline Dilated Cardiomyopathy (DCM) Decrease in calcium influx to cardiac myocytes. Impaired sensitivity of contractile protein to calcium ion. Decrease in number of cardiac myocytes due to apoptosis. Heart failure

Retina Visual system Lens Tapetum Lucidum Feline central retinal degeneration (FCRD) Retina Tapetum Lucidum Visual system Lateral geniculate body Superior colliculus Lens

Feline central retinal degeneration (FCRD)

Tapetum lucidum normal Taurine deficiency

Immune system Leucopenia Decrease respiratory burst of neutrophils Decrease phagocytic activity of phagocytes

Reproductive System & Development Taurine-deficient pregnant queen Kittens born from taurine- deficient female cats More incidences of fetal death (resorption), abortion, or stillbirth. Reduction of taurine concentration in feline maternal milk. Low survival rate Low birth weight Growth retardation Bone malformation Impaired nervous and visual system development. Kitten obtain taurine from the queen In other species, the placenta provides the fetus with essential nutrients. The mechanism by which the queen supplied taurine to the kittens in utero was not known. This work was conducted in collaboration with scientists at the University of Manchester (Champion et al. 2004; Champion et al.2005). Taurine uptake was characterised in placental fragments obtained from queens during normal parturition. For the first time, it was shown that the cat placenta possesses amino acid transport systems that are functionally similar to the system β and system A transporters of the human placenta (Champion et al. 2004).

Kittens born from taurine-deficient female cats. A premature kitten with congenital hydrocephalus. A stillbirth kitten with anencephaly. Severe congenital hydrocephalus, a brain from 1-year old kitten. Kitten obtain taurine from the queen In other species, the placenta provides the fetus with essential nutrients. The mechanism by which the queen supplied taurine to the kittens in utero was not known. This work was conducted in collaboration with scientists at the University of Manchester (Champion et al. 2004; Champion et al.2005). Taurine uptake was characterised in placental fragments obtained from queens during normal parturition. For the first time, it was shown that the cat placenta possesses amino acid transport systems that are functionally similar to the system β and system A transporters of the human placenta (Champion et al. 2004).

Effects on digestive physiology Nutritional Aspects Recommended amount Commercial diets Bioavailability Ingredients Processing Dry diet Effects on digestive physiology Canned diet Processing

Taurine Requirement for Cats The Association of American Feed Control Officials (AAFCO)  Growth and Reproduction Adult Maintenance Nutrient Minimum Maximum Taurine (extrude,%) 0.10 Taurine (canned,%) 0.20 AAFCO Nutrient requirements are indicated on a dry-matter basis. These AAFCO nutrient profiles for cat foods presume an energy density of 4.0 kcal ME/g dry matter. By comparison, the average mature body weight of domestic cats is 3.2 kg (7 lb) for toms and 2.8 kg (6 lb) for queens. Normal birth weight of kittens is 90–100 g. The growth rate is exceptionally rapid for the first 3–4 mo, and kittens gain 50–100 g/wk. The growth rate begins to plateau at 150–160 days of age, and growth is usually completed within 200–220 days.

How to prevent taurine deficiency in cats? Nutritional Aspects How to prevent taurine deficiency in cats? Commercial diets Homemade meal Processing

Taurine amount labelled on Hill’s commercial cats diets

Taurine amount in food (mg/kg, wet weight)

Case study Feline Dilated Cardiomyopathy History taking Domestic male cat, 4 years old, 3.8 kg. body weight Signs of depression, poor appetite, cough, and dyspnea since 3 weeks ago. The cat has muffled cardiac sound. The owner had fed the cat with commercial dog food for 1 year and 6 months.

Examination Thoracic radiograph shows severe fluid accumulation in pleural space. Electrocardiography shows decrease in 'R' wave amplitude Echocardiography shows incress in EDV = End diastolic volume or LVIDd  ↓ , ESV = End systolic volume or LVIDs  ↓ and shortening fraction ↑ Hematology and Serum biochemical parameter are normal Direct opthalmoscopic is normal

Shortening fraction Measurement Normal LVIDd (cm) 2.45 1.59 ± 0.19 LVISd (cm) 2.27 0.80 ± 0.14 ∆ D (%) 8.5 49.8 ± 5.3

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