PENTOSE PHOSPHATE PATHWAY AND NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE Flashcards
an alternative pathway to glycolysis for breaking down glucose
Pentose Phosphate Pathway (Hexose Monophosphate Shunt)
a reducing agent that is essential for many cellular processes, such as the synthesis of fatty acids and cholesterol, and the detoxification of reactive oxygen species.
NADPH
a precursor for the synthesis of nucleotides, which are the building blocks of DNA and RNA.
ribose 5-phosphate
In this phase, glucose 6-phosphate is converted to ribose 5- phosphate and NADPH. Carbon 1 of glucose 6-phosphate is released as CO2.
Oxidative phase
In this phase, ribose 5-phosphate can be converted back to glucose 6-phosphate, or it can be used to synthesize other five-carbon sugars
Non-oxidative phase:
is required for the synthesis of fatty acids and cholesterol.
NADPH
is a series of biochemical reactions that convert glucose 6-phosphate(G6P) to produce ribose 5-phosphate (R5P), NADPH, and other molecules.
PPP
(irreversible; produces NADPH)
Oxidative phase
(reversible)
Converts ribulose 5-phosphate (Ru5P) into ribose 5-phosphate (R5P).
Non-oxidative phase
first step in the pentose phosphate pathway, and it produces NADPH
Dehydrogenation of glucose 6-phosphate
an enzyme that catalyzes the oxidation of glucose 6-phosphate to 6- phosphogluconolactone.
Glucose 6-phosphate dehydrogenase (G6PD)
is a competitive inhibitor of G6PD.
NADPH
When the NADPH/NADP+ ratio is high, G6PD activity is ______
inhibited
When the NADPH/NADP+ ratio is low, G6PD activity is _______
increased.
If insulin is increased, it upregulates the expression of G6PD ____ the amount of G6PD protein that is produced in the cell.
increases
second step in the oxidative phase of the pentose phosphate pathway, and it produces NADPH.
Formation of ribulose 5-phosphate
6-Phosphogluconolactone is hydrolyzed by
6-phosphogluconolactone hydrolase.
Oxidation of 6-phosphogluconate to ribulose 5-phosphate is catalyzed by
6-phosphogluconate dehydrogenase.
allow the cell to convert ribulose 5-phosphate (produced by the oxidative phase of the pathway) to either ribose 5-phosphate (needed for nucleotide synthesis) or to intermediates of glycolysis (fructose 6-phosphate and glyceraldehyde 3- phosphate)
REVERSIBLE NON- OXIDATIVE REACTIONS
If the cell needs more NADPH than ribose 5-phosphate:
the transketolase and transaldolase enzymes will convert ribulose 5-phosphate to glyceraldehyde 3-phosphate and fructose 6-phosphate, which can then be fed into glycolysis to produce NADPH.
If the cell needs more ribose 5-phosphate than NADPH:
then the transketolase and transaldolase enzymes will convert glyceraldehyde 3-phosphate and fructose 6-phosphate to ribose 5-phosphate
is a coenzyme that is similar to NADH, but it has an additional phosphate group.
NADPH
Some examples of reductive biosynthetic reactions that use NADPH include:
Fatty acid synthesis
Cholesterol synthesis
Nucleotide synthesis
Amino acid synthesis
is the process of building molecules by adding hydrogen atoms.
REDUCTIVE BIOSYNTHESIS
is a reactive oxygen species (ROS) that can damage cells.
Hydrogen peroxide (H2O2)
NADPH is used by the enzyme ______ to reduce H2O2 to water.
glutathione peroxidase
is found in all cells in the body, and it is especially important in cells that are exposed to high levels of ROS, such as liver cells.
Glutathione peroxidase
A condition in which there is an imbalance between ROS production and ROS detoxification. contribute to a variety of diseases, including cancer, heart disease, and Alzheimer’s disease
Oxidative stress
Uses NADPH to reduce hydrogen peroxide (H2O2) to water. This protects cells from the damaging effects of H2O2.
Glutathione peroxidase
Regenerates reduced glutathione, which is used by glutathione peroxidase to reduce H2O2. NADPH is also used in this reaction.
Glutathione reductase
Converts superoxide to H2O2. Superoxide can damage cells even more than H2O2.
Superoxide dismutase
Converts H2O2 to water and oxygen.
Catalase
Antioxidant chemicals
Ascorbate (vitamin C)
Vitamin E
β-carotene
Reduces ROS, including H2O2 and superoxide.
Ascorbate (vitamin C)
Vitamin E
β-carotene
is a process by which white blood cells (such as neutrophils) engulf and kill bacteria and other foreign particles.
This is an important part of the immune system’s defense against infection.
Phagocytosis
These mechanisms use pH changes in phagolysosomes and lysosomal enzymes to destroy pathogens.
Oxygen-independent mechanisms
These mechanisms use the enzymes NADPH oxidase and myeloperoxidase (MPO) to generate reactive oxygen species (ROS), which kill bacteria
Oxygen-dependent mechanisms
rare genetic disorder caused by a deficiency in NADPH oxidase. People with CGD are more susceptible to severe, persistent infections.
Chronic granulomatous disease (CGD)
Highly reactive molecules that can damage cells. produced as byproducts of normal metabolism, but they can also be produced in response to stress or exposure to toxins.
Reactive oxygen species (ROS)
A vesicle formed by the fusion of a phagosome and a lysosome.
Phagolysosome
contain bacteria or other foreign particles that have been engulfed by the cell.
Phagosomes
contain enzymes that can break down bacteria and other foreign particles.
Lysosomes
is a gas produced by many cells in the body, including the lining of blood vessels, nerve cells, and immune cells.
Nitric oxide (NO)
NO causes blood vessels to relax and widen, which _____blood flow to tissues.
increases
has a very short half-life in the body, meaning that it breaks down quickly. This is because it is a free radical, which means that it has an unpaired electron
NO
is an enzyme that produces nitric oxide (NO).
Nitric oxide synthase (NOS)
3 types of NOS:
Endothelial NOS (eNOS)
Neuronal NOS (nNOS)
Inducible NOS (iNOS)
is found in the lining of blood vessels and produces NO to keep blood vessels open and relaxed.
Endothelial NOS (eNOS)
is found in nerve cells and produces NO to regulate nerve signaling.
Neuronal NOS (nNOS):
is found in many cells, including macrophages and neutrophils, and is produced in response to infection or inflammation
Inducible NOS (iNOS)
NO causes blood vessels to relax and widen, which increases blood flow. It does this by activating an enzyme called guanylate cyclase, which produces
cyclic guanosine monophosphate (cGMP).
is a signaling molecule that causes smooth muscle cells in the blood vessel walls to relax.
cGMP cyclic guanosine monophosphate
are immune cells that help to fight infection. iNOS produces NO in macrophages, which can kill bacteria and other pathogens.
Macrophages
- is a X-linked genetic disorder characterized by hemolytic anemia caused by the inability to detoxify oxidizing agents.
G6PD deficiency
is a condition in which the body’s red blood cells are destroyed faster than they can be replaced
Hemolytic anemia
If G6PD activity is ___ , red blood cells are more likely to be damaged by free radicals.
reduced
NADPH is used to reduce:
glutathione (GSH)
an antioxidant that helps to neutralize free radicals
glutathione (GSH)
Commonly used drugs that produce hemolytic anemia in patients with G6PD deficiency: “AAA”
antibiotics (for example, sulfamethoxazole and chloramphenicol),
antimalarials (for example, primaquine), and antipyretics (for example, acetanilid).
the hemolytic effect of ingesting fava beans, is not observed in all individuals with G6PD deficiency
Favism
is the most common precipitating factor of hemolysis in G6PD deficiency
Infection
