Advanced Nutrition- Topic 9 (Free Radicals & Antioxidants)

What form of Vitamin C is unusable by the body? What antioxidant _______________(or 2GSH)____ reduces this form back to ascorbic acid?

dehydroascorbic acid Glutathione reacts with dehydroascorbic acid to reduce back to Vit C

Superoxide radicals are generated in areas where lots of oxygen are available. Where would this be located?

electron transport chain in MITOCHONDRIA.

How are free radicals generated? Where are they generated?

formed via normal cellular metabolic reactions, oxidative stress, & environmental exposure (smoke, alcohol) occurs in the mitochondria of cells as part of the electron transport/respiratory chain.

Vitamin E deficiency

hemolytic anemia (plasma membrane has low integrity so it RBC's are easily broken down)

tyrosine is synthesized from ______________?

phenylalanine in cells

Vitamin C deficiency is:

scurvy (bruising/hemmorhage, bleeding gums) because of weak collagen in the skin. & microcytic anemia

What are some antioxidant defenses?

- Enzymes (catalase, superoxide, dismutase, and glutathione peroxidase) - Glutathione - Vitamins A, C, and E - Other antioxidants

Phytochemical examples: & their sources? Flavonoids

- blue, red, or yellow pigments (anthocyanins & anthoxanthins) - chocolate, tea, grape juice/wine, F/V - some are broken down by COLONIC microflora - anti-inflammatory and anticancer properties

Ways to get rid of hydroxyl radicals:

-use of ascorbic acid to convert hydroxyl to water - glutathione (an antioxidant) (Ex. --> converts dehydroascorbic acid to ascorbic acid again)

Free radicals can mainly increase from 3 sources: ______________(1), ___________(2), and _____________(3).

1. environmental stressors 2. normal cellular metabolism & processes 3. immune system defense

What occurs with excessive ROS? (3) What occurs with inadequate ROS? (3)

Cell death, diseases, aging Impaired immune function, impaired cell proliferation, other impaired responses

Which enzyme breaks up hydrogen peroxide into water and oxygen?

Catalase (an iron-dependent enzyme in the liver)

Vitamin E can be easily destroyed by exposure to a. air b. heat c. light d. all of the above What functional group gets destroyed from this exposure?

D. all of the above the phenolic ring gets destroyed, so protection is needed (ex. cool, dark storage to keep light away from plant oils)

What kinds of bonds are free radicals attracted to? Where are they located?

Double bonds which are located in almost every cell of the body

Superoxide dismutase (SOD): Catalase: Glutathione peroxidase: is dependent on what metal?

Extracellular SOD= copper-zinc dependent (in the cytosol) Mitochondrial SOD= manganese-dependent (in mitochondria) Catalase= iron-dependent (peroxisome in liver cells) GPX= selenium-dependent (uses glutathione)

Are phytochemicals considered nutrients? T/F

FALSE, they are considered non-essential nutrients They are plant-derived health promoting substances that suppress diseases and bring beneficial antioxidants to body. Should not consume phytochemical substances b/c of unknown adverse effects. Consuming variety of plant-based foods should suffice in quantity.

Beta carotene is a precursor for vitamin

Pro-Vitamin A

What are all the different reactive species besides ROS? (other elements)

Reactive oxygen species (ROS) Reactive nitrogen species (RNS) Reactive sulfur species (RSS) Reactive carbon species (RCS)

What is the reduced form of glutathione? What is the oxidized form of glutathione?

Reduced= 2GSH Oxidized= GSSG

What is a typical body process that contributes to the rise of free radicals?

Respiration

Selenium is metabolized by sulfur-containing amino acids, methionine and cysteine. Selenium is a co-factor for enzymes like _______________(1) and ___________(2), which are important for oxidant defense mechanisms. Beneficial for AIDS pts) Selenophosphate plays a role in metabolism and synthesizes __________(1).

1. glutathione peroxidase (GPX) 2. thioredoxin reductase 3. selenocysteine

Damage to DNA can lead to mutation in SOD (superoxide dismutase), which can cause what disease?

Amyotrophic lateral sclerosis (ALS)= a motor neuron disease

Superoxide dismutase (SOD) does what?

An enzyme that converts superoxide radicals to less active form (ex. h2o2 and O2) H2o2 can still be damaging but is more easily rid of in the body

What is a common antioxidant that converts ROS to a non-damaging form?

Glutathione peroxidase

Reduced form of superoxide radicals (H202, O2) must be regenerated to active form again (superoxidized radical). T/F

T/F

Glutathione is a tripeptide that consists of (3)? What does it do? It is the strongest marker for oxidative stress and most abundant antioxidant found in cells.

glycine, cysteine, and glutamate residues reducing agent that can help reverse radical formation before damage is done to the cell and neutralizes peroxide

Hydrogen Peroxide can react with superoxide to form _____________?(highly reactive)

hydroxyl radical

Oxidized/reduced LDL is the more potent source of causing oxidative stress, so higher risk of ASCVD.

oxidized LDL

What factors increase free radicals in the body?

oxidized LDL cholesterol, heavy recreational drug & alcohol use, body processes in rxn to medications, & high exposure to sunlight

Carnitine synthesis is used to

to break down fatty acid by transporting FA from cytoplasm to mitochondria for breakdown

What are the two forms of vitamin E? What do they have in common and differences? What are the sources of Vit E?

tocopherols (have SAT FAs) and tocotrienols (have UNSAT FAs) Both contain phenolic ring. plant-based foods (plant oils, nuts, seeds, F/V, etc.

What are free radicals?

unstable molecules with unpaired electrons that can damage the cells of the body and contribute to increased risk of chronic diseases

Alpha-tocopherol is the active form of Vit E. When it is fully spent, it is converted to a radical. To regenerate Vit E, what nutrients are needed?

vitamin C, glutathione, and NAPDH NAPDH can be found from pentose phosphate pathway.

Extracellular SOD mechanism requires _____&_______ to destroy superoxide radicals

zinc and copper

_________ is a good metalloenzyme to assist ascorbate in the hydroxylation of these amino acids. Hydroxylases require this as a cofactor. Requires a proper state to function. Ascorbate reduces this metal from (2+ to 3+) during reaction.

Iron (Fe)

What reactions generate hydrogen peroxide?

It can be generated by the - elimination action of superoxide dismutase - reactions involving ascorbate (Vit C)--> eliminates SOD - reactions in peroxisomes (involving FA's, trauma, & injury) - catalyzation of amine oxidases (during neurotransmitter synthesis)

What are endogenous sources of ROS? (4)

Mitochondria, Peroxisomes NADPH oxidase Other enzymes

Beta-carotene is twice the size of Vitamin A. When split in half, it can produce two vitamin A. so is beta-carotene and vit A the same molecule?

No. Pro-vitamin A= beta-carotene; functions as an antioxidant Vitamin A itself is not biologically used by the body.

___________ (a type of FA's) found in the plasma membrane are an area that can attract free radical (thus oxidative damage)

PUFA's have many sites of unsaturation that have more available electrons (so free radical are more readily available)

Only alpha-tocopherol has antioxidant biological activity. T/F

TRUE

Production of radicals can breed more radicals. T/F

True

Hydrogen peroxide is a reactive oxygen species but it is not a radical. T/F.

True, H2O2 has no unpaired electrons, so it is not a radical.

Having too many antioxidants can provoke cancers, etc.. T/F

True, antioxidants are important to reduce oxidative stress. BUT too much can be just as harmful. Once again, balance is key for need of both free radicals AND antioxidants.

Free radicals can be generated in any part of the cell. T/F

True, it can be all parts of the cell, not just membranes, aqueous solutions, mitochondria or nucleus. It can be generated anywhere.

Superoxides are NOT lipid soluble, thus do not diffuse too far away from site of production. T/F

True, they are locally diffused.

Reactive Oxygen Species (ROS)

Unstable oxygen-containing molecules that can cause cellular damage, including damaging our DNA

Hydroxylation of lysine + proline

Vit C's role in Collagen production

Activated WBC's such as: (3) , use large amounts of oxygen to generate substantial amounts of ____________ _________as foreign substances are taken up for destruction via phagocytosis. What is this process called?

WBC: neutrophils, macrophages, monocytes WBC's generate superoxide radicals to destroy foreign bodies. The respiratory or oxidative burst

Excess fat-soluble substances (vitamins) can be converted into substances that exit out of body through _______ and then as feces.

bile

Glutathione peroxidase (GPx)

converts hydrogen peroxides and hydroperoxides from tissues into harmless molecules (H2O and O2)

Hydroxyl radical has a very __short/long__ (1) half-life, however, it is the most potent reactive radical.

shortest half-life; strongest damage inflicted - can cause mutation or dysfunction of proteins

Vitamin E as an antioxidant, terminates peroxidase reactions and singlet molecular oxygen destruction. (protection against free radical) It also plays a role in ______________ (1), _______________(2), and ___________(3).

signal tranduction

Phytochemical examples: & their sources? Indoles & Alliums

- allium: garlic/onions - sulfur-containing (STRONG smells) - found in cruciferous vegs, garlic, onions, leeks & shallots - INDOLES= inactivate estrogen - ALLIUMS= boost cancer-destroying enzyme activity & prevent gut bacteria from converting nitrates to nitrites

Vitamin C is required for what kinds of synthesis? (4)

- collagen synthesis - carnitine synthesis - tyrosine synthesis & - Neurotransmitter synthesis (norepinephrine) - Microsomal metabolism

What reactions generate hydroxyl radical?

- exposure to gamma rays (ex. phones) - reactions involving superoxide & other electrons/protons - reactions involving free iron or copper

Phytochemical examples: & their sources? Phytoestrogens

- include isoflavones & lignins - found in soybeans, flaxseeds, and barley. - help with menopause & osteoporosis (blocks estrogen receptors) - may also protect against breast cancer - needs further study on those who have negative effects with estrogen

Regeneration of 4 main antioxidants include (4):

- vitamin E regeneration - glutathione regeneration - vitamin C regeneration - ubiquinol & thioredoxin regeneration

Superoxide radicals is generated in which reactions? (Name at least 3)

- when electrons leak out in ETC -reactions involving folate and THF - reactions involving cytochrome p450 - production of catecholamines - immune system reactions (respiratory/oxidative burst--> WBC activation)

Phytochemical examples: & their sources? Carotenoids

- yellow-orange pigments - carotene, lycopene, lutein, zeaxanthin - found in F/V, and some fish and birds - vitamin A activity - reduce risk of some cancers, CVD, and age-related eye diseases

Regeneration of Glutathione

-Glutathione reductase -Uses NADPH generated from the hexosemonophosphate shunt (PPP)

Pro-vitamin A (from carotenoids) as an antioxidant quenches singlet molecular oxygen & free radicals, which is generated from: _____________(1), _______________(2), ________________(3).

1. lipid peroxidation (in WBC's), 2. neutrophil activation 3. photochemical reaction (in the eyes)

It would be preferrable to have zero oxidative stress. T/F.

False, balance is key. The body requires some level of oxidative stress for normal functioning. If inadequate level of ROS--> impair immune function, greater risk for infectious dz, cell proliferation & other processes that depend on free radical rxns.

What are reactive oxygen species used for in cells? Name some examples.

ROS are essential for many defense mechanisms in cells. Ex: immune systems attacking foreign molecules Ex: body processing toxic chemicals in liver

What are exogenous sources of ROS production?

UV light, ionization radiation, drugs, inflammatory cytokines, environmental toxins

Does a higher ratio of oxidized form of glutathione (GSSG) indicate greater risk of dz? What does a higher ratio of GSH (reduced form) do?

Yes, too much oxidative stress can lead to dz. GSH, the reduced form, in RBS's can optimize the regeneration of antioxidants (like Vit E)

What are the eight main neurotransmitters? What are they associated with at dangerous levels?

acetylcholine (a/w Alzheimer's dz) dopamine (a/w Parkinson's dz) GABA, glutamate (both a/w epilepsy & seizures) histamine, (a/w allergic response) norepinephrine (a/w euphoria or anxiety/depression) serotonin & dopamine (a/w mood disorders)

Excess oxidative stress can lead to __________, however, some oxidative stress is necessary to maintain __________________of free radicals.

disease homeostatic release

Hydroxyl radical can attack prolines and histidine in proteins, thus causing a ____________ of protein.

dysfunction or mutation

Lycopene, lutein, zeaxanthin are: Which one is the most effective quencher?

effective quenchers; pigments and phytochemicals found in carotenoids that can reduce macular degeneration and improve eye health Lycopene is the most effective (red pigment found in tomatoes)

The cytochrome p450 system is needed for metabolism of FA's, steroids, and therapeutic drugs in the conversion of nonpolar to polar compounds for ______________ (through feces or urine).

elimination

Vitamin C, a water soluble antioxidant can provide electrons to convert radical to h202 and o2. Vitamin C requires a metalloenzyme involving a metal cofactor (_______ or _________) that needs to be in a reduced state to regenerate the enzyme back in the original state that it needs to be.

iron and copper cofactors

Reactive oxygen species (ROS) are generated in smaller/larger amounts when tissue injury or damage occur, especially involving ischemia (inadequate blood flow, thus oxygen supply)

larger

Hydrogen peroxide can move very freely into ________ phase (and water/aqueous phase) and can cause ___localized/ubiquitous___ damage to lipids throughout the body

lipid phase damage is ubiquitous (occuring throughout the whole body)

Vitamin E is a/w protection of which parts of the body? because of the high degree of unsaturated fatty acids.

lungs, RBC, and brain protection These areas have higher degree of unsaturation, metabolism and oxygen presence. It also maintains integrity of plasma membrane

Mitochondrial SOD mechanism requires __________ to destroy superoxide radicals

manganese

The superoxide radical is an ___________-centered radical and forms when moleculer oxygen reacts with different compounds These reactions involve production of catecholamines: ___________ & _____________ ; reactions involving folate as tetrahydrofolate; ______________ p450 catalyzed reactions; some rxns of the ETC and those needed in immune system.

oxygen-centered (e.g. the unpaired electron resides on the oxygen) - dopamine & epinephrine - cytochrome p450

Ascorbic acid allows hydroxylation of amino acids in collagen, such as _________ & __________. When hydroxylated, it forms prolyl hydroxylase and lysyl hydroxylase to form these cross-links of collagen fibrils for tensile strength. Vitamin C has an essential role in connective tissue healing, being a cofactor for prolyl and lysyl hydroxylase. These enzyme catalyze the hydroxylation of proline and lysine residues of procollagen.

proline and lysine