 Contents :

 Introduction
 Irreversible oxidative phase
 Reversible phase
 Important of NADPH
 Summary of carbohydrate metabolism

By: Savath Sovannak

 Pentose phosphate pathway (Hexose monophosphate shunt = HMP shunt) : Consists of a
group of reactions in which G6P is degraded, leading to the formation of
 NADPH (nicotinamide adenine dinucleotide phosphate)
 Ribose-5-phosphate : is needed for synthesis of nucleotides
 Location : cytosol of al cells
 HMP shunt ែចក� 2 phases :
 Irreversible oxidative phase :
o containts 3 irreversible reaction
o Net reaction: G6P + 2NADP+ + H2O→ ribulose 5-phosphate + 2NADPH + 2H+ + CO2
 Reversible (nonoxidative) phase
o Reversible reactions permit ribulose 5-phosphate to be converted either to ribose
5-phosphate or to intermediates of glycolysis
o Net reaction: 3 ribulose 5-phosphate ⇄ ribose 5-phosphate + 2 xylulose 5-
phosphate ⇄ 2 fructose 6-phosphate + glyceraldehyde 3-phosphate
 Note : There is no ATP is used or generated in HMP shunt

By: Savath Sovannak

 G6P dehydrogenation
 G6P is oxidized to 6-phosphogluconolactone by enzyme G6PD (G6P dehydrogenase)
o NADP+ is reduced to NADPH + H+
o G6PD :
• Stimulated by : G6P, NADP+
• Inhibited by : NADPH
 Ribulose-5-phosphate formation
 6-phosphogluconolactone is hydrolyzed by 6-phosphogluconolactone
hydrolase​(lactonase)  form 6-phosphogluconate
 6-phosphogluconate is oxidized and decarboxylated by 6-phosphogluconate
dehydrogenase  form Ribulose-5-P, second NADPH + H+, CO2

By: Savath Sovannak

  Function depend on cell’s
need :
 Creation of ribose 5-
phosphate from
ribulose 5-phosphate
(used for nucleotide
synthesis)
 Create sugars that
can be exchanged
between the pentose
phosphate pathway
and glycolysis

 Main reactions :
 Ribulose 5-phosphate ⇄ ribose 5-phosphate (isomerization reaction) via ribose 5-
phosphate isomerase
 Ribulose 5-phosphate ⇄ xylulose 5-phosphate (epimerization reaction) via ribulose 5-
phosphate epimerase (phosphopentose epimerase)
 Ribose 5P + Xylulose 5P ⇄ Sedoheptulose 7P + Glyceraldehyde 3P by transketolase
 Sedoheptulose 7P + Glyceraldehyde 3P ⇄ F6P + Erythrose 4P by transaldolase
 Xylulose 5P + Erythrose 4P ⇄ F6P + Glyceraldehyde 3P by transketolase
By: Savath Sovannak
 Contents :
 Biosynthesis of :
o Fatty acid
o Cholesterol
o Steroid hormone
o Nucleotide
o Nitric oxide (NO)
o Bile acid synthesis
o Bilirubin synthesis
 Cytochrome P45O monooxygenase system
 Free radical and antioxidant
 Phagocyte killing bacteria

By: Savath Sovannak

 Cytochrome : � redox-active protein containing heme
 Cytochrome P450 monooxygenases (CYPs) : are family of enzyme containing heme as a
cofactor
 Function : incorporate one atom from 02 into a substrate

 Location : Smooth endoplasmic reticulum and mitochondria

1. Mitochondrial system:
 Biosynthesis of steroid hormone : convert cholesterol to pregnenolone by
CYP11A1 (testes, ovaries, adrenal cortex)
 Convert 25(OH)D to 1,25(OH)D by 1-hydroxylase (CYP27B1) at proximal tubule of
kidney
2. Microsomal system (Smooth endoplasmic reticulum)
 Detoxification of foreign compounds (xenobiotics) esp drug in liver

 Bile acid synthesis at liver

 Convert vit-D2 and D3 to 25(OH)D at liver
By: Savath Sovannak
 Free radicals : are atoms or molecule containing one or more unpaired electrons in an outer
shell .
 Reactive oxygen species (ROS) : specific type of free radical and non-free radical containing
Oxygen atom

 Source :
 Endogenous :
o Redox reactions
o Immune cell activation
o Ischemia
o Inflammation
 Exogenous :
o Radiation exposure
o Drug
o Sun exposure
o Pollution
o Food

By: Savath Sovannak

 Free radical  cell damage by :
 DNA damage
 Cell membrane damage : direct damage and lipid peroxidation (auto-oxidation)
 Mitochondrial membranes damage: lipid peroxidation
 Cellular proteins modification
 Microvascular injury

 Elimination of free radical by anti-oxidant

 Note : when free radical or ROS is higher than anti-oxidant by increase free radical
formation or decrease amount of anti-oxidant  called oxidative stress
 Type of anti-oxidant :
 Enzymatic :
o Superoxide dismutase (SOD)
o Catalase
o Glutathione peroxidase
 Nonenzymatic :
o Vitamins : E,A,C
o Mineral : manganese, copper, Zinc, Selenium
By: Savath Sovannak
 Enzymatic antioxidant

 SOD :
o �ន 2 isozyme :
• SOD-1 in cytosolic and need
copper and zinc as coenzyme
• SOD-2 in mitochondria and
need manganese as coenzyme
o Convert superoxide to oxygen and
hydrogen peroxide
 Catalase : convert hydrogen peroxide to
oxygen and water
 Glutathione peroxidase
o Need selenium as coenzyme
o Can act on hydrogen peroxide, lipid hydroperoxide and lipid peroxide radical
o Glutathione peroxidase take electron from 2 reduced glutathione (G-SH) to
hydrogen peroxide  from water + oxidized glutathione (G-S-S-G)
• In order to get G-SH back we need NADPH and enzyme glutathione reductase
o To lipid hydroperoxide and lipid peroxide radical are the same as to hydrogen
peroxide By: Savath Sovannak
 Vitamin
 Reduced form of vitamin E (EH)
react with lipid peroxide radical 
form Lipid hydroperoxide and free
radical tocopheroxy radical
 Vitamin C and A can convert free
radical tocopheroxy radical back to
reduced form EH

By: Savath Sovannak

 Phagocyte : neutrophil and macrophage
 Kill bacteria by 2 mechanism : oxygen-independent and oxygen-
dependent
 Oxygen-independent : use pH changes in phagolysosomes and
lysosomal enzymes to destroy pathogens
 Oxygen-dependent : use ROS
 Bacteria bind it to a receptor on a phagocytic cell 
internalization of the microorganism
 Then NADPH oxidase, located in the leukocyte cell membrane, is
activated and reduces O2 from the surrounding tissue to
superoxide េ�យ យក electron from NADPH
 Next superoxide is convert hydrogen peroxide either
spontaneously or catalyzed by superoxide dismutase
 Then H2O2 can convert to hypochlorous acid (HOCl) or hydroxyl
radical
 Note : all ROS has produced is able to kill bacteria

By: Savath Sovannak

By: Savath Sovannak
By: Savath Sovannak