Exam 3 Biochem-Lecture 26 – Flashcards
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Unlock answersWhat are alternates names for Pentose Phosphate Pathway? |
-Hexose Monophosphate Shunt -6-Phosphoroglucontate pathway |
Pentose Phosphate Pathway Products include: |
•NADPH for reductive biosynthesis -fatty acids and steroids •Ribose-5-phosphate -Nucleic Acids •Glycolytic Intermediates -glyceraldehyde-3-phosphate -Fructose-6-phosphate |
Higher requirement for NADPH than ribose-5-phosphate |
1) complete oxidation of G6P to CO2 2) resynthesis of G6P and ribulose-5-P. |
| Higher requirement for ribose-5-P than NADPH |
G6P is converted to fructose-6-P and glyceraldehyde-3-P by glycolytic pathway |
| Pentose Phosphate Pathway has ...... stages |
| 2 |
Pentose Phosphate Pathway Stage I |
Decarboxylation of hexose to pentose yielding NADPH. IRREVERSIBLE |
| Pentose Phosphate Pathway Stage II |
|
| Glucose-6-Phosphate Dehydrogenase |
•Catalyzes the first step in the pentose phosphate pathway •Rate limiting step •Uses NADP as a cofactor (reaction generates NADPH) •Highly regulated by NADPH/NADP ratio |
| NADPH/NADP ratio = high |
| inhibits G6PD |
| NADPH/NADP ratio= low |
| activates G6PD |
NADPH |
Primarily uses high energy electrons for biosynthesis: –Fatty Acids –Steroids |
NADH |
•Uses high energy electrons to make energy (ATP via oxidative phosphorylation) |
| Functions of NADPH |
•Provide high energy electrons for reductive biosynthesis •Used as a cofactor by enzymes that deal with reactive oxygen species (ROS)
These functions cannot be replaced by NADH |
| Reactive Oxygen Species |
I.) Superoxide Anion II.) Hydrogen Peroxide III.) Hydroxyl Radical |
Superoxide Anion
O2- |
------produced biologically by a variety of reactions most notably by “leaky”mitochondrial electron transfer. Electrons can be Transferred from the reduced form of Coenzyme Q to oxygen, thus generating superoxide. |
Hydrogen Peroxide
H2O2 |
| produced by oxidase enzymes. Very toxic organic peroxides can be formed from 2e- reduction of O2 in compounds containing double bonds (unsaturated fatty acids). |
Hydroxyl Radical OH- |
produced from a metal catalyzed reaction of superoxide and hydrogen peroxide. Very reactive species that can take part in free radical chain reactions. |
Glutathione: A Multifunctional Peptide |
|
| Cellular Defense Against Oxidative Stress |
I.Superoxide Dismutase (SOD)-detoxifies superoxide II. Catalase-heme containing peroxidase that detoxified H2O2 III. There are no known enzymatic systems that deal directly with hydroxyl radicals. Cells rely on the above two reactions to remove precursors to ROS> |
| Cu-ZnSOD (cytoplasmic enzyme) |
enzyme deficiency leads to severe progressive neurodegenerative disorder: Lateral Sclerosis (ALS) or Lou Gherig’s Disease |
| Cytochrome P-450 System |
• Liver enzymes detoxify many nasty compounds: -Drugs -Steroids -Alcohols •These enzymes require NADPH as a cofactor. |
| Lack of G6PD results in |
|
| X-linked disease |
is the most common disease causing enzymatic defect in humans (200 million people world wide) |
Hemolytic anemia can be precipitated by: |
|
G6PD Mutations |
•Many mutations alter G6PD function. •Many alter the Km and Vmax of the enzyme •Some mutations confer resistance to flaciparum malaria |
| Drugs that have effect on G6PD |
–e.g., sulfamethoxazole
–e.g. primaquine, chloroquine
–e.g. acetanilide |
| Drugs that has no effect on G6PD |
| aspirin or acetaminophen |
| Glucuronic Acid |
| conjugated to endogenous and exogenous compounds producing a strongly acidic compound that is more water soluble at physiological pH than its precursor |
Glucuronic Acid is Important in: |
–Drug detoxification –Steroid excretion –Bilirubin metabolism |
