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

Nutrition Concepts in Signal Transduction

©C. Murray Ardies, 2014

Graphic from: Biochemistry by Mary K. Campbell

To synthesize all of the components of cells we have toeat the right things.

A Cellular Model of Nutrition – Carbs, Lipids, Proteins


A Cellular Model of Nutrition – Vitamins & Minerals


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


Some of the signaling pathways are well known such as the insulinand epinephrine pathways

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.

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!

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…

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


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

Two other major antioxidant compounds that help to reduce the damage are β-Carotene and Glutathione


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.


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…


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.


Dietary Notes On Some Antioxidant Vitamins

RDA Food Sources

Ascorbic Acid 75 & 90 mg/day ♀ & ♂ Citrus fruits and strawberries, tomatoes, potatoes, broccoli, cauliflower, spinach,cabbage, and Brussels sprouts

α-tocopherol 15 mg/day ♀ & ♂ Vegetable oils and wheat germ

Carotenoids N/A Tomatoes, green & yellow vegetables(ß-carotene, lutein,lycopene . . .)


Food Group Sources of Antioxidant Compounds

Dairy Fruits Veggies Meats & Beans & Nuts & Breads & Oils Eggs Legumes Seeds Cereals

Ascorbic Acid X Green

α-tocopherol X X (vegetable)

Selenium X X

Carotenoids greenyellow


Dietary Notes On Requirements for Some Antioxidant Enzymes

RDA Food Sources

Iron 18 & 8 mg/day ♀ & ♂ Dried fruits, nuts, cereal products, - component of catalase organ & other meats, seeds, green

leafy vegetables

Zinc 11 & 8 mg/day ♀ & ♂ Wheat germ, whole grains, beef,- component of cytosolic & poultry, oystersextracellular superoxide dismutase Copper 900 ug ♀ & ♂ Whole grains, liver, legumes, eggs, - component of cytosolic & meats, shellfishextracellular superoxide dismutase

Manganese 1.8 & 2.3 mg/day ♀ & ♂ Wheat bran, nuts, poultry, legumes,- component of mitochondrial meat superoxide dismutase

Selenium 35 µg/day ♀ & ♂ Seafood, organ and red-meats, whole - component of glutathione peroxidase grains, dairy


Food Group Sources of Minerals for Antioxidant Enzymes

Dairy Fruits Veggies Meats & Beans & Nuts & Breads & Oils Eggs Legumes Seeds Cereals

Iron X X X X XGreenleafy

Zinc X Xbeef/poultryoysters

Copper X X Xeggs/meatsshellfish

Manganese X X Xbeef/poultry

Selenium X X Xorgan/red meatsfish


Unfortunately, the average American diet

Really Sucks . . .


With obvious results,,,

AntioxidantVitamins

Minerals for Antioxidant & Redox ControlEnzymes


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.

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.

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…..

Ya gotta do this…

Number of Food Servings for Daily Caloric Intakes:

Food Group Standard Approximate ~ 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 Fats 1 Tbsp (EVOO) 110 2 2 3 3

Discretionary Calories - - 200 400


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

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