SKIN ENERGY SUPPLEMENT INCREASING OXYGEN USE & ENERGY FROM MITOCHONDRIA. AGI Dermatics THIOTAINE

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THIOTAINE DOSSIER Barnet Products Corporation 140 Sylvan Avenue Englewood Cliffs NJ 07632 Tel 201 346 4620 Fax 201 346 4333 Web barnetproducts.com Presents SKIN ENERGY SUPPLEMENT INCREASING OXYGEN USE & ENERGY FROM MITOCHONDRIA AGI Dermatics THIOTAINE The information contained in this technical bulletin is, to the best of our knowledge, true and accurate. No warranty, expressed or implied is made or intended. The use should be based upon the customer s own investigations and appraisal. No recommendation should be construed as an inducement to use a material in infringement of patents or applicable government regulations.

THIOTAINE DOSSIER - 1 INTRODUCTION OXYGEN, ENERGY & WELL-BEING PART ONE: Thiotaine and Mitochondria a) The Powerhouse: Mitochondria b) Thiotaine: Natural Amino Acid PART TWO: The Dual Role of Thiotaine a) Role in Energy Production and Fatty Acid Transport b) Role in Anto-Oxidation and Mitochondria Protection PART THREE: Thiotaine, Anti-Stress Molecule a) Reducing Solar Stress b) Reducing Oxidative Stress PART FOUR: Thiotaine, A Clarifying Molecule CONCLUSION BIBLIOGRAPHY

THIOTAINE DOSSIER - 2 INTRODUCTION: OXYGEN, ENERGY AND WELL-BEING Energy is the moving force of life. It is a fundamental and indispensible element in cellular activity. All cells must produce energy to survive, and oxygen consumption is fundamental to the process. In our daily life we associate oxygen with outdoor activity. We go to the mountains for fresh air. In trendy shopping areas we can visit oxygen bars. Oxygen is associated with health, with looking and feeling good. It is also known that Olympic long-distance runners train in the mountains to increase the oxygen levels in their blood to help give them a competitive edge. Energy and oxygen are related and Thiotaine is a molecule that helps assure efficient use of oxygen for more efficient energy production. This action also assures the wellbeing of the cells.

THIOTAINE DOSSIER - 3 PART ONE: THIOTAINE AND MITOCHONDRIA a) Power House and Energy Production ATP (Figure 2) is an energy transporter in the cell (Figure 1). As a result of its high energy bonds, it releases energy during its hydrolysis according to the following transformation: As a common denominator between catabolism and biosynthesis, the ATP level is a faithful indicator of physiological dynamics. The cells draw energy from the metabolizing of carbohydrates, lipids and proteins in order to synthesize ATP (see below). ATP - a universal cellular fuel - participates in all intercellular reactions of biosynthesis (keratin, ceramides), and in the transport of substances across membranes as well as in the exchanges between the cells and their environment. So the cells incorporate nutrients more easily and discharge their metabolic wastes. Thus, the epidermis is cleansed. ATP is made in special organelles in the cells called mitochondria. ATP is synthesized from AMP and phosphate by burning faty acids with oxygen, called aerobic metabolism. To increase ATP production it is important to increase the presence of fatty acids in the mitochondria. Thiotaine is a molecule that transfers fatty acids into the mitochondria to help use oxygen efficiently and to produce more energy. Without mitochondria, energy is generated by anaerobic metabolism, which is inefficient and generates toxic wastes.

THIOTAINE DOSSIER - 4 Figure 1 Figure 2: ATP Chemical Structure

THIOTAINE DOSSIER - 5 b) Thiotaine - Natural Amino Acid Thiotaine is the trade name for pre-solubilized L-ergothioneine (Figure 3). CH 2 -CH-COO - N N N + (CH 3 ) 3 S Figure 3: L-ergothioneine chemical structure * L-ergothioneine can be found in botanicals such as mushrooms, vegetables and grain. * L-ergothioneine is a dietary requirement. * L-ergothioneine is concentrated in red blood cells to protect hemoglobin. * Unlike many molecules with a Thiol group, Thiotaine is odorless, tasteless, water-soluble and stable. * Thiotaine has two functional groups: ---a transferring group: N-(CH 3 ) 3 (red dotted line) ---an anti-oxidant group: Thiol

THIOTAINE DOSSIER - 6 PART TWO - THE DUAL ROLE OF THIOTAINE a) Role in Energy Production and Fatty Acid Transport The transferring group of Thiotaine - CH 3 - N + - CH 3 - is also present in Carnitine CH 3 Carnitine is used in slimming products. It helps to transfer fatty acid in the mitochondria and the oxygen present will burn the fatty acid.

THIOTAINE DOSSIER - 7 Carnitine s mode of action is described below. Fatty Acids (CH 2 ) COOH + Co ASH Fatty Acyl Co A + Carnitine Fatty Acyl Carnitine + Co ASH Transfer into Mitochondria Fatty acylcarnitine + Co ASH Fatty acids CoA+ Carnitine Fatty acid + O 2 majority CO2 + ATP minority O (oxygen radical) Consequence: Less Fatty Acid; More Energy

THIOTAINE DOSSIER - 8 Thiotaine s mode of action is similar. Fatty alcyl CoA + Thiotaine Penetrates the Mitochondria Fatty acyl Thiotaine + Co ASH Fatty acyl Thiotaine + Co ASH Fatty acids CoA + Thiotaine control of oxidative stress O* Fatty acid + O2 CO2 + ATP Consequence: Less Fatty Acid, More Energy But Also: Control of Oxidative Stress by the second group of Thiotaine: The Thiol

THIOTAINE DOSSIER - 9 Thiotaine will shift fatty acids in mitochondria to increase the aerobic metabolism existing in the mitochondria.

THIOTAINE DOSSIER - 10 PROTOCOL Thiotaine, like carnitine, pushes the fatty acid into the mitochondria. The fatty acids are "burned" with oxygen and the result is the production of energy (ATP). With Thiotaine, this activity is increased by 16.5%

THIOTAINE DOSSIER - 11 The Anti-Oxidant Group of Thiotaine b) Role in Anti-Oxidation and Mitochondria Protection S - H Oxygen is good for metabolism and ATP synthesis But it also counteracts the sideeffect of oxygen metabolism, which is the production of free radicals. Thiotaine has a Thiol group; therefore, it has anti-oxidant properties. Lipid Peroxides % Control 120 100 80 60 40 20 N-acCys L-Met BME BHT L-Cys MgAscPO4 Thiotaine 0 Antioxidant Powercheck All of the above molecules (except MgAscPO 4 ) contain Thiol antioxidant activity. Most of them have a strong characteristic odor. None perform as well as Thiotaine when challenged with an oxidizing treatment (in this case, 20 µm alloxan).

THIOTAINE DOSSIER - 12 Thiotaine is an antioxidant, protecting the mitochondrial membrane against oxidation. (Note: Alloxan is an oxidant) Thiotaine: Mitochondrial Protection Mouse keratinocytes stained with mitochondrial dye JC-1 Mitochondria are healthy. Cells treated with alloxan, killing mitochondria with oxygen radicals. The yellow color indicates the death of mitochondria due to oxidation. Cells treated with Thiotaine and alloxan are protected. The mitochondria are not damaged by the oxidant. CONCLUSION We have demonstrated that Thiotaine not only participates in the consumption of oxygen to produce energy, but Thiotaine also acts as an anti-oxidant, especially as a protector of the mitochondria. The hemoglobin molecule, a carrier of oxygen in the blood, uses Ergothioneine as a protector.

THIOTAINE DOSSIER - 13 PART THREE: THIOTAINE: ANTI-STRESS MOLECULE In this section we will discuss two different expressions of stress. a) UV-B Stress UV induces damage to many parts of the cell. The skin responds to this stress by releasing signals called cytokines. TNF-Alpha (Tumor Necrosis Factor) is one such type. These cytokines cause the inflammation of skin that follows stress. Thiotaine reduces TNF-Alpha, a stress signal cytokine 120 100 Percent TNFalpha Induction 80 60 40 20 UV-B 100 J/m 2 UV+1% Thiotaine 0 Thiotaine Reduces Stress Signals

THIOTAINE DOSSIER - 14 The second approach is to consider the consequences of oxidation. b) Inflammation OXIDATION ACTIVATION OF MACROPHAGES RELEASE OF OF ELASTASE HO CL Elastase (the destroyer of elastin) is under the control of a group of enzymes called Alpha Anti-Proteinase-1. Protecting the AP-1 is like preserving the elastin and avoiding aging. HO CL destroys Alpha Anti-Proteinase-1; therefore, elastase is activated and the aging process begins. Thiotaine is a HO CL chelator, amplifying the power of Alpha Anti-Proteinase-1 as an anti-elastase material (as shown on the next page). Inflammation, even if it is not easily seen, causes attacking cells to enter the skin. These macrophages cause the release of enzymes, like elastase, that destroy the supporting structure of skin. This leads to the appearance of aging skin. Thiotaine controls the release of elastase during an inflammatory attack. It preserves the skin defenses, especially the protein Alpha AP-1, the primary defense against elastase.

THIOTAINE DOSSIER - 15

THIOTAINE DOSSIER - 16 PART FOUR: THIOTAINE AS A CLARIFIER Clarifier: Thiotaine acts like a clarifier because it is: * A metal chelator like Kojic Acid * An antioxidant like Vitamin C * It inhibits tyrosinase and also inhibits melanin in cell cul ture at 1% use level 5 Melanin (pg/cell) 4 3 2 1 0 None Melanin Induction Plus Thiotaine