Other name for the Pentose Phosphate Pathway
Hexose MonoPhosphate (HMP) shunt
This pathway is a branch off of the
glycolytic pathway
The two main purposes of this pathway are:
- Generation of NADPH
2. Generation of the 5-C sugar ribose (to be used in synthesis of nucleotides)
Depending on the needs of the cell, the pathway can produce:
Either:
-both ribose and NADPH
or
-either NADPH or ribose
The net total ATP used and produced in this pathway is
zero; none are produced or used
Name the Oxidative Irreversible Reactions of HMP
Step 1: Dehydrogenation of Glucose 6-P
Step 2: Hydrolysis to 6-phosphogluconate
Step 3: Oxidative decarboxylation of 6-phosphogluconate
Name the enzyme responsible for Step 1 of the Oxidative Irreversible Reaction:
Glucose 6-phosphate dehydrogenase (G6PD)
Which step within the Oxidative Irreversible Reactions of HMP is the rate-limiting step?
Step 1: Dehydrogenation of Glucose 6-P
Which enzyme within the Oxidative Irreversible Reactions requires NADP+ as a coenzyme?
Glucose 6-phosphate dehydrogenase (G6PD)
What molecule is a potent competitive inhibitor within Step 1 of the Oxidative Irreversible Reactions?
NADPH
Expression of G6PD is upregulated by
insulin
The flux of G6PD through the pathway is increased in the
absorptive state
Name the enzyme responsible for Step 2 of the Oxidative Irreversible Reaction:
6-phosphogluconolactone hydrolase
Name the enzyme responsible for Step 3 of the Oxidative Irreversible Reaction:
6-phosphogluconate dehydrogenase
Which steps within the HMP pathway are irreversible?
Steps 1-3: Oxidative Irreversible Reactions
- Dehydrogenation of Glucose 6-P
- Hydrolysis to 6-phosphogluconate
- Oxidative decarboxylation of 6-phosphogluconate
Steps 4-8 of the HMP pathway are considered the
Nonoxidative Reversible Reactions
Steps 4-8 are responsible for
Interconversions of sugar molecules
Describe the Nonoxidative reversible reactions within HMP:
- reversible steps
- interconvert sugars w/3-7 C-atoms
- permit synthesis of ribose 5-P used for nucleotide production
The enzyme responsible for steps 4-8 of HMP is:
Transketolase
This enzyme requires TPP from thiamine
Transketolase
Transketolase is important for
diagnosing thiamine deficiency
Name the functions of NADPH:
- Electron donor for the “reductive” biosynthesis of fatty acids, cholesterol, steroids
- Electron donor for neutralization of reactive oxygen species
- Provides reducing equivalents for Cytochrome P450 Monooxygenase system (for biosynthesis of steroids, detox xenobiotics)
- Play role in phagocytosis (destruction of pathogens by macrophages and neutrophils)
- Substrate for synthesis of nitric oxide (NO)
When are reactive oxygen species produced?
During aerobic metabolism, through reactions with drugs and toxins, when levels of antioxidants are diminished
____ is the major antioxidant system
Glutathion (GSH/GSSG)
_____ is an enzyme that will incorporate 1 O-atom from molecular oxygen (creating -OH group) w/the other being reduced to H2O.
Monooxygenase
Cyt P450 systems:
_____ system: the synthesis of steroids
Mitrochondrial
Cyt P450 systems:
_____ system: detoxification of foreign compounds
Microsomal
This Cyt P450 system is associated with the inner mitochondrial membrane.
Mitochondrial Cytochrome P450
Mitochondrial Cytochrome P450 in the liver
uses the same system to synthesize bile acids and Vitamin D3
Mitochondrial Cytochrome P450 in the kidney
converts vitamin D3 to its active form
Mitochondrial Cytochrome P450 in steroidogenic tissues (placenta, ovaries, testes and adrenal cortex)
uses NADPH for synthesis of steroid hormones
This Cyt P450 system is associated with the membranes of the smooth ER in liver cells
Microsomal system Cytochrome P450
This system is responsible for the detoxification of drugs, toxins and other chemicals.
Microsomal System Cytochrome P450
In the microsomal system cytochrome p450, by adding ____, the compound may be inactivated (or activated), made more soluble, or provide a reactive group for attachment of other molecules.
oxygen (hydroxyl groups)
NADPH plays a role in phagocytosis within these cells
White Blood Cells (neutrophils and macrophages)
NADPH role in phagocytosis:
-generates ______ that aid in killing microorganisms they have engulfed.
oxygen free radicals
The MPO system is a combination of:
NADPH oxidase and myeloperoxidase
The MPO system is used to
generate oxygen free radicals to aid in destruction of microorganisms
Rare genetic NADPH oxidase deficiency causes
Chronic Granulomatous Disease (CGS)
The granuloma in ____ is formed as a defense where the body attempts to “wall off” the collection of cells from the rest of the body
CGS: Chronic Granulomatous Disease
CGS causes
persistent severe infections due to the inability to kill bacteria forming granulomas
___ is synthesized from arginine, oxygen and NADPH
NO (Nitric Oxide)