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Nutrition Concepts in Signal Transduction
©C. Murray Ardies, 2014
To synthesize all of the components of cells we have to
eat the right things.
Graphic from: Biochemistry by Mary K. Campbell
A Cellular Model of Nutrition – Carbs, Lipids, Proteins
©C. Murray Ardies, 2014
A Cellular Model of Nutrition – Vitamins & Minerals
©C. Murray Ardies, 2014
Cellular proteins are extremely important because they
perform many of the essential functions of a cell
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…
©C. Murray Ardies, 2014
Some of the signaling pathways are well known such as the insulin
and 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 ST 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
©C. Murray Ardies, 2014
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
©C. Murray Ardies, 2014
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
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
In order to ensure that we can maintain
appropriate levels of our antioxidant
compounds, antioxidant enzymes, and redoxsensor proteins we need to have the proper
nutrients.
©C. Murray Ardies, 2014
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
(ß-carotene, lutein,
lycopene . . .)
Tomatoes, green & yellow vegetables
©C. Murray Ardies, 2014
Food Group Sources of Antioxidant Compounds
Dairy
Ascorbic Acid
Fruits
Veggies
X
Green
Meats & Beans & Nuts &
Eggs
Legumes Seeds
α-tocopherol
X
Selenium
Carotenoids
Breads & Oils
Cereals
X
X
(vegetable)
X
green
yellow
©C. Murray Ardies, 2014
Dietary Notes On Requirements for Some Antioxidant Enzymes
Iron
component of catalase
RDA
Food Sources
18 & 8 mg/day ♀ & ♂
Dried fruits, nuts, cereal products, organ & other meats, seeds, green
leafy vegetables
Zinc
11 & 8 mg/day ♀ & ♂
- component of cytosolic &
extracellular superoxide dismutase
Copper
900 ug
component of cytosolic &
extracellular superoxide dismutase
Manganese
- component of mitochondrial
superoxide dismutase
♀&♂
1.8 & 2.3 mg/day ♀ & ♂
Selenium
35 µg/day
- component of glutathione peroxidase
♀&♂
Wheat germ, whole grains, beef,
poultry, oysters
Whole grains, liver, legumes, eggs, meats, shellfish
Wheat bran, nuts, poultry, legumes,
meat
Seafood, organ and red-meats, whole
grains, dairy
©C. Murray Ardies, 2014
Food Group Sources of Minerals for Antioxidant Enzymes
Dairy
Iron
Fruits
Veggies
X
X
Green
leafy
Meats &
Eggs
Beans &
Legumes
X
X
Zinc
X
beef/poultry
oysters
Copper
X
eggs/meats
shellfish
Manganese
X
X
beef/poultry
Selenium
X
Nuts &
Seeds
Breads &
Cereals
Oils
X
X
X
X
organ/red meats
fish
X
X
X
©C. Murray Ardies, 2014
Unfortunately, the
average American diet
Really Sucks . . .
©C. Murray Ardies, 2014
With obvious results,,,
Antioxidant
Vitamins
Minerals for Antioxidant & Redox Control
Enzymes
©C. Murray Ardies, 2014
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…..
Number of Food Servings for Daily Caloric Intakes:
Food Group
Standard
Serving Size
Approximate
Calories /
Serving
~ 2000
kcal
~ 2200
kcal
~ 2500
kcal
~ 2800
kcal
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
on remaining days)
3 ounces
120
-
-
-
-
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
110
2
2
3
3
-
-
200
400
Added Fats
1 Tbsp (EVOO)
Discretionary Calories
Ya gotta do this…
©C. Murray Ardies, 2014