the first reaction of the oxidation reaction is catalyze by
glucose-6- phosphate dehydrogenase
what is the coenzyme with glucose 6 phosphate dehydrogenase that is used in the 1st and second reactions
NADP+
it gets reduced to NADPH + H+
the ____ ____ reactions occur in cells that synthesize nucleotides and nucleic acids
reversible nonoxidative
cells that actively synthesize fatty acids or cholesterol (liver, adrenal cortex, adipose tissue, lactating mammary gland) or cells that are exposed to high pO2 (danger of free radical production) utilize to a significant degree the _____ ____ reactions of the PPP
oxidative irreversible
the reversible, non oxidative set of reactions produces ____ and links to_____
nucleotides
glycolysis
the irreversible oxidative pathway causes
reduction of NADP+ to produce NADPH
NADPH and NADH have the same ___ ____ but are ______ distinct
redox potential
metabolically
NADPH utilizes its reductive potential for the synthesis of ______ and as an ______
fatty acids
anti oxidant
the irreversible oxidative pathway of the PPP is responsible for converting ______ to ______
glucose-6 phosphate
6 phosphogluconate
the rate of mitochondrial DNA mutation is _____ than nuclear DNA
why? (2)
higher
**bc it is the area of the ETC (free radical forms)
**it doesn't have the repair systems of the nucleus
what is the enzyme that breaks up superoxide (substrate for this enzyme)
superoxide dismutase (SOD)
superoxide dismutase converts superoxide to what?
Oxygen
hydrogen peroxide
what is the enzyme that breakdowns hydrogen peroxide (substrate for this enzyme)
catalase
catalase breaks down hydrogen peroxide into what?
oxygen and water
true/false: the pretense of ROS in different disease states does not necessarily prove causation of those diseases by ROS
TRUE
what is the most reactive ROS
hydroxyl radical
ROS Damage includes (3)
mutation of dna
peroxidation of lipids
fragmentation of proteins and cross-linking
the cytochrome p450 monooxygenase system consists of 2 portions
inner mitochondrial cytochrome p450
ER associated cytochrome
what is the inner portion of the cytochrome p450 involved with?
the hydroxylation of steroids (cholesterol, steroid hormones, vitamin D, etc)
^^dont over look, he will test on this
physically significant antioxidants (7)
vitamin A (carotene)
vitamin E (tocopherol)
vitamin C (ascorbic acid)
uric acid
glutathione
lipoic acid
ubinquinol
where do the cyps in the liver come from?
cytochrome p450
glutathione is a tri peptide of what three AA?
glutamate, cysteine, glycine
Reduced glutathione converts ______ to _____ with the enzyme glutathione peroxidase
hydrogen peroxide
water
_____ ______ regenerates oxidized glutathione
Glutathione peroxidase
_____ _____ regenerates reduced glutathione
Glutathione reductase
and oxidizes NADPH and H+ to NADP+
Xenobiotic-metabolizing cytochrome P450 proteins are bound to the membranes of the ______ _____ _____in the liver, the lungs (because you breath it in), the small intestine, and other organs.
smooth endoplasmic reticulum
hydroxylation of xenobiotics (phase one reactions) can (3)
increase the water solubility for excretion in bile or urine
activate a pro drug
deactivate a drug
True/False: hydroxylation can also cause procarcinogens can also be activated into carcinogens
TRUE
depends on the cup alleles you have on whether it does something good or bad
the water solubility of the xenobiotic can be enhanced by conjugation with water soluble compounds as glucuronic acid, sulfate, glycine, glutamine, glutathione, etc
this is know as the ____ __ reaction
phase 2
where do phase 1 and 2 reactions occur?
smooth ER
True/False: a phagolysosome is still a lysosome
TRUE
still a lysosome just has a phagosome in it
the respiratory burst uses superoxide which is created from
NADPH being oxidize by NADPH oxidase and O2 being reduces to make superoxide
what is the enzyme in the lysosome that helps covert H2O2 to OCl-
Myelo-peroxidase
The O2- spontaneously forms _____
H2O2
don’t need an enzyme for this (just adding electrons to O2-)
H2O2 forms _____ with addition of ____ that can kill the bacteria
OCl-
Cl-
H2O2 also forms ___ free radical (while oxidizing ferous iron to ferric iron) that can kill the bacteria
OH-
Heinz body-containing erythrocytes are often characterized by ______ ______ _____ and are targeted for destruction by spleen macrophages
ROS-generated membrane deformities
___ ___ is produced by the catalytic oxidation of L-Arg to L-citrulline using oxygen and NADPH as substrates
nitric oxide (NO)
What are the three NO synthases:
eNOS: found in endotheliial cells
nNOS: found in neurons
iNOS: inducible found in many types of cells
eNOS: found in endotheliial cells is ____ (synthesized at a constant rate, and is not induced or inhibited); _____ dependent
and is always on not _____ or _____
constitutive
calcium
induced or repressed
nNOS: found in neurons are _____ and _____ dependent
constitutive
calcium
iNOS: inducible, can function independently of ____
calcium
True/False: NO is actually a free radical
TRUE
why does NO have to act in very short distances (autocrine and paracrine) rather than in the endocrine system
because it has a short half life
what are 4 functions of NO
1. relaxes smooth muscle (vasodilator)
2. prevents plaque build up (to avoid clots)
3. functions as a neurotransmitter in the brain
4. mediates tumoricidal and bactericidal actions of macrophages
most prevalent human genetic enzyme deficiency
glucose 6 phosphate dehydrogenase deficiency
G6PDD deficiency is found in about ___ of all ___ ___ males
