1. Nutrition Concepts in Signal Transduction © C. Murray Ardies, 2014

2. Graphic from: Biochemistry by Mary K. Campbell To synthesize all of the components of cells we have to eat the right things.

3. A Cellular Model of Nutrition – Carbs, Lipids, Proteins © C. Murray Ardies, 2014

4. A Cellular Model of Nutrition – Vitamins & Minerals © C. Murray Ardies, 2014

5. There are literally thousands and thousands of different proteins; each one with a different order of amino acids, a different shape, and a different function, some of which include: Enzymes to perform chemical reactions Actin and myosin (and others) to make up the contractile proteins Collagen and fibrin for connective tissue Antibodies for binding to foreign or “non-self” shapes DNA-binding molecules to regulate transcription/translation And cellular receptors which include the many proteins that are embedded into the cellular membrane that function to initiate a signal-transduction pathway: insulin receptors, epinephrine receptors, estrogen receptors, testosterone receptors, etcetera, etcetera, etcetera… Cellular proteins are extremely important because they perform many of the essential functions of a cell © C. Murray Ardies, 2014

6. Some of the signaling pathways are well known such as the insulin and epinephrine pathways

7. ERK-MAPK - p38 MAPK - JNK-MAPK - PI3K/Akt Not so well known are the signal-transduction pathways that regulate transcription and translation of many different proteins: the ERK-MAPK, p38-MAPK, JNK-Mapk, PI3K/Akt, and the “Nfκβ” pathways. These STPs regulate synthesis of the many proteins that are necessary for maintaining cell function and for producing proinflammatory molecules following various stresses. They also regulate synthesis of proteins in our stem cells and progenitor cells that are necessary for the different functions of cell division.

8. A sequence of DNA molecules codes for a sequence of amino acids of a protein. Different sequences of DNA molecules (genes) code for different proteins (gene products). Transcription of DNA sequence into mRNA sequence is tightly controlled by a variety of transcription factors (proteins) than can initiate, enhance, or repress transcription; transcription factors that are in turn controlled by a variety of metabolic, hormonal, or other signaling processes. Just imagine what might happen if you screw up any of the processes of metabolism, or hormone function, or signal transduction, or get toxic damage to the structure of any DNA base!

9. Regulation of Signal Transduction (S-T) Pathways Activities of S-T pathways are regulated by a variety of growth factors, hormones, calcium, and ROS. Note that both Calcium and ROS affect enzymes that activate S- T pathways. Thus control of Calcium and of ROS are very important for controlling S-T. If excessive S-T activity happens for an extended period of time (many hours to many days; or all the time…) then they will produce a variety of inflammatory signaling molecules that produces an inflammatory response… Leading to even more disregulated S-T activity and more ROS…

10. DAMAGE A variety of molecules that are produced through normal biological functions can lead to damage… Reactive oxygen species (ROS) from inflammatory cells, from normal metabolic reactions, and even from sources outside the body can cause damage. Some of the ROS and Calcium can disrupt the signal transduction pathways by interfering with their normal regulation © C. Murray Ardies, 2014

11. The major antioxidant nutrients that help to reduce damage from ROS are Vitamin E & Vitamin C. These compounds help to maintain the cellular redox state within “normal;” limits… and because normal metabolic reactions of cells constantly produce a variety of Reactive Oxidant Species (ROS) these vitamins are essential for normal cellular function. They also help to get rid of ROS that enter the cell from other sources such as inflammatory cells. © C. Murray Ardies, 2014

12. Two other major antioxidant compounds that help to reduce the damage are β-Carotene and Glutathione © C. Murray Ardies, 2014

13. Antioxidant / Redox Control Enzymes A variety of antioxidant & redox control enzymes are synthesized in cells in order to help maintain the cellular redox state within “normal” limits… Thioredoxin (Trx), Peroxyredoxin (Prx), Glutathione Peroxidase (GPX), Superoxide Dismutase (SOD), and Catalase (CAT) are essential enzymes that control the redox state of a cell. They also help to get rid of ROS that enter the cell from other sources such as inflammatory cells. © C. Murray Ardies, 2014

14. Thioredoxin and Peroxyredoxin are very important regulators of the p38 and JNK S-T pathways in addition to being important antioxidant proteins… In a sense, they are cellular redox sensors that help to quench ROS when there are elevated levels of them and they also enhance the p38 and ERK S-T pathways when there are elevated levels of ROS to help produce the proper response… © C. Murray Ardies, 2014

15. In order to ensure that we can maintain appropriate levels of our antioxidant compounds, antioxidant enzymes, and redox- sensor proteins we need to have the proper nutrients. © C. Murray Ardies, 2014

16. Dietary Notes On Some Antioxidant Vitamins RDAFood Sources Ascorbic Acid75 & 90 mg/day ♀ & ♂ Citrus fruits and strawberries, tomatoes, potatoes, broccoli, cauliflower, spinach, cabbage, and Brussels sprouts α-tocopherol15 mg/day ♀ & ♂ Vegetable oils and wheat germ Carotenoids N/ATomatoes, green & yellow vegetables (ß-carotene, lutein, lycopene...) © C. Murray Ardies, 2014

17. Food Group Sources of Antioxidant Compounds DairyFruitsVeggiesMeats &Beans &Nuts &Breads & Oils Eggs LegumesSeeds Cereals Ascorbic AcidXGreen α-tocopherolXX (vegetable) SeleniumXX Carotenoidsgreen yellow © C. Murray Ardies, 2014

18. Dietary Notes On Requirements for Some Antioxidant Enzymes RDAFood Sources Iron18 & 8 mg/day ♀ & ♂ Dried fruits, nuts, cereal products, - component of catalaseorgan & other meats, seeds, green leafy vegetables Zinc11 & 8 mg/day ♀ & ♂ Wheat germ, whole grains, beef, - component of cytosolic &poultry, oysters extracellular superoxide dismutase Copper 900 ug ♀ & ♂Whole grains, liver, legumes, eggs, - component of cytosolic &meats, shellfish extracellular superoxide dismutase Manganese1.8 & 2.3 mg/day ♀ & ♂ Wheat bran, nuts, poultry, legumes, - component of mitochondrial meat superoxide dismutase Selenium35 µg/day ♀ & ♂ Seafood, organ and red-meats, whole - component of glutathione peroxidase grains, dairy © C. Murray Ardies, 2014

19. Food Group Sources of Minerals for Antioxidant Enzymes DairyFruitsVeggiesMeats &Beans &Nuts &Breads & Oils Eggs LegumesSeeds Cereals Iron X X X X X Green leafy Zinc X X beef/poultry oysters Copper X X X eggs/meats shellfish Manganese X X X beef/poultry SeleniumX X X organ/red meats fish © C. Murray Ardies, 2014

20. Unfortunately, the average American diet Really Sucks... © C. Murray Ardies, 2014

21. With obvious results,,, Antioxidant Vitamins Minerals for Antioxidant & Redox Control Enzymes © C. Murray Ardies, 2014

22. Insufficiencies in antioxidant and redox control-related nutrients lead to exaggerated ST responses as well as enhanced damage due to lack of protection from excessive oxidizing agents.

23. Too many antioxidant nutrient and antioxidant compounds can lead to insufficient ST-responses due to stressors and lead to inadequate stress responses and to inadequate protection from oxidizing agents.

24. Only through optimal nutrient intake can appropriate regulation of STP-activities will occur along with both enhanced redox control and enhanced protection from various oxidants will result. So… if you want this…..

25. Ya gotta do this… Number of Food Servings for Daily Caloric Intakes: Food Group StandardApproximate~ 2000~ 2200~ 2500~ 2800 Serving Size Calories/ kcal kcal kcal kcal Serving Fruits 0.5 cup 71 5 5 5 5 Vegetables 0.5 cup 38 6 6 6 6 Cold-Water Fish 4 ounces 120 2/wk 2/wk 2/wk 2/wk (Optional: Lean Meats 3 ounces 120 - - - - on remaining days) Nuts & Seeds 0.25 cup 240 1 1 1 1 Beans & Legumes 0.5 cup 110 2 3 3 3 Dairy 1.0 cup/2 oz. 86 3 3 3 3 Breads & Cereals 1 slice/1 oz 78 5 6 7 7 Red Wine 4 oz 85 1 1 1 1 Added Fats1 Tbsp (EVOO) 110 2 2 3 3 Discretionary Calories - - 200 400 © C. Murray Ardies, 2014