session 17

what good processes are O2 essential for

- oxidative phosphorylation

- biosynthesis

- detoxification

what bad processes are O2 derived reactive oxygen species and free radicals result in

- damage of cellular components

- aging

- neurodegenerative diseases

- respiratory diseases

- cell death

what are radicals

compounds that contain a single (unpaired) electron, usually at an outer orbital; they are highly reactive. Free radicals are radicals capable of independent existence, but often short-lived in a biological system

what are reactive oxygen species (ROS)

comprise of both highly reactive oxygen radicals and compounds that are readily converted to those reactive radicals

is O2 considered a true radical

Oxygen contains 2 unpaired electrons but it has an even total number of electrons; it is NOT regarded as a true radical but a ROS

O2 classification

Biradical ROS

O2- superoxide classification

radical

H2O2 hydrogen peroxide classification

Non-radical; ROS

·OH hydroxyl radical classification

radical

H2O water classification

non radical- stable

what is the most reactive species

hydroxyl radical OH•

what are organic radicals

RO•, R•, R-S

what is nitric oxide

NO, reactive nitrogen-oxygen species

what is ischemia reperfusion injury

caused directly by cytotoxic ROSs derived from oxygen in the blood that reperfuses previously hypoxic cells. It may also occur when tissue oxygenation is suddenly restored during surgery or transplantation

diseases are multifactorial diseases. ___ or ___ is one of the factors.

other factors include:

ROS; RNOS

Genetic factors; environmental factor; physiological factor; life-style factor; etc

what are the major sources of primary ROSs and radicals

1. Generated by non-enzymatic reactions

2. Accidental by-products of normal enzymatic reactions

3. Deliberate production under special circumstances

what are examples of nonenzymatic production of ROS

Haber Weiss, Fenton, generation of hydroxyl radical by UV ionizing radiation and lightening

nonenzymatic production can occur:

both inside or outside of a biological system

how does sunscreen work

By absorbing the UV energy

how does the detoxification of drugs, alcohol, and xenobiotics occur

by cytochrome P450 enzymes in the smooth ER

ROSs and RNOSs do collateral damage to _______ cells/tissues

surrounding

superoxide and the hydroxyl radical initiate lipid peroxidation in the cellular, mitochondrial, nuclear, and endoplasmic reticulum ______

membranes

Damage to _______ systems by internal or external ROSs and radicals has grieve consequences

membrane

The decrease of ___________ is related to aging and many other disease states

membrane fluidity

________ is an important signaling molecule or hormone

dopamine

Cellular Defenses against Oxygen Toxicity: what is cellular compartmentation

physically separating ROSs from the rest of cell, e.g. peroxisome

Cellular Defenses against Oxygen Toxicity. what is metal sequestration

immobilizing Fe to ferritin and hemosiderin

Cellular Defenses against Oxygen Toxicity. what is Antioxidant defense enzymes

converting ROSs to nontoxic products, e.g. SOD

Cellular Defenses against Oxygen Toxicity. what is Dietary and endogenous antioxidants

terminating free radical chain reactions, e.g. vitamin A, vitamin C, vitamin E, glutathione

Cellular Defenses against Oxygen Toxicity. what is Repair of damaged cellular components

through degrading and new synthesis

what are high sources of vitamin e

Seeds/oils, nuts, fruits and vegetables

what are high sources of vitamin c

Fruits (particularly oranges) and leafy vegetables

what are high sources of vitamin a

Liver, eggs, fruits and vegetables (particularly carrot)

what are high sources of flavonoids

Berries, tea, fruits and vegetables

what are examples of endogenous antioxidants

uric acid and melatonin

what is free radical disease

damage caused to proteins and lipids owing to free radical generation may lead to cellular dysfunction

what is parkinson disease

inability to convert tyrosine to DOPA; DOPA treatment can temporarily reverse tremors and other symptoms

what is myocardial infarction

further damage to heart can occur because of free radical generation after oxygen is reintroduced to the cells that were temporarily ischemic: ischemia reperfusion injusry

what is chronic granulomatous disease

reduced activity of nicotinamide adenine dinucleotide phosphate oxidase, leading to a reduction in the oxidative burst by neutrophils, coupled with a dysregulated immune response to bacteria and fungi

what is respiratory distress syndrome of a newborn

either mutations in surfactant or lack of surfactant production in newborns; lungs have difficulty inflating and compressing

what is amytrophic lateral sclerosis (ALS)

familial form caused by mutations in superoxide dismutase, leading to difficulty in disposing of superoxide radicals which leads to cell damage owing to excessive reactive oxygen species

what is age related macular degeneration

oxidative damage occurs in the retinal pigment epithelium, leading first to reduced vision then to blindness

what is haber weiss reaction

non enzymatic radical production

super oxide + hydrogen peroxide produces oxygen, water, and hydroxyl radial (·OH)

what is the fenton reaction

metal used to turn hydrogen peroxide into hydroxide ion and hydroxyl radical (·OH)

how are radicals formed by metabolic by products

FAD → ·FADH → FADH2

or accidental generation of superoxide in ETC by CoQ

how does CYP450 create radicals

• CCl4 enters the blood and become CC3l·

• occurs due to CYP450 in the liver

• damages hepatocytes

• causes decrease in protein synthesis

long fatty acid chains are shortened by _____ to produce shorter chains. this process produces _____

oxidase; hydrogen peroxide

what is lipid peroxidation

a free radical chain reaction

the oxidative degradation of lipids—particularly polyunsaturated fatty acids (PUFAs) in cell membranes—by reactive oxygen species (ROS) or enzymes. This process steals electrons from lipids and triggers a destructive chain reaction that compromises cell structure and function

what does less dopamine result in

being less sensitive to stimuli