Carbohydrates- Pentose Phosphate Pathway Flashcards
What is the pentose phosphate pathway?
- Alternative pathway of glucose metabolism
- Distinct from glycolysis
- Does not produce ATP
- Does not oxidise glucose completely
- Cytosolic pathway in all cells
What does the pentose phosphate pathway generate?
- Pentose (5C) phosphates for the synthesis glucose-6-phosphate
- NADPH (from NADP+)
At what point in glycolysis does the PPP branch from?
- glucose-6-phosphate
- Hexose monophosphate shunt
How can PPP intermediates be recycled into mainstream of glycolysis?
- Conversion of intermediates into fructose-6-phosphate or glyceraldehyde-3-phosphate
- Important for RBC and quiescent cells with little need for DNA and RNA
How much glucose within RBC is shunted through PPP and why?
- About 10%
- Generate NADPH for reduction of glutathione (GSH is an essential molecule for antioxidant defence)
- Allows anabolic and catabolic reactions to occur simultaneously
What type of cells undergo PPP?
- All types including RBC
What is the difference between NADPH and NADH?
- Addition of phosphate group
- No effect on electron carrier capability of either molecule
- NAD- catabolic - NADP- anabolic
What is the purpose of the phosphate group on NADPH?
- To distinguish the molecules and allow them to interact with different sets of enzymes
What is the purpose of having both NAD and NADP?
- At any given time- single cell can have access to both oxidising and reducing agents for both anabolic and catabolic reactions
What is the first stage of PPP?
- An irreversible redox stage
- Yields NADPH and pentose phosphates
What is the second stage of PPP?
- Reversible interconversion stage
- Excess pentose phosphates converted to glycolytic intermediates
- Only used when NADPH is needed but not pentose phosphate, e.g. RBC
What does the non-oxidative stage do?
- Recycles excess pentose phosphates into glycolysis intermediates
What enzyme is used to divert glucose-6-phosphate molecule down oxidative stage of PPP?
Glucose-6-phosphate dehydrogenase
What does the final reaction of redox produce?
Ribulose-5-phosphate (5 carbon sugar)
- In cells with active nucleic acid synthesis, ribulose-5-phosphate is isomerism to ribulose-5-phosphate
What is ribose-5-phosphate used for?
- Used for synthesis ribo and deoxyribo- nucleotides for DNA and RNA
What is a transaldolase deficiency?
- Abnormally low levels of transaldolase enzyme involved in interconversion stage of PPP
- Autosomal recessive (very rare- consanguineous)
How does a transaldolase deficiency present?
- Growth retardation
- Dysmorphic features
- Cutis laxative’s
- Congenital heart disease
- Hepatosplenomegaly
- Pancytopenia
- Bleeding tendency
- Non-specific features means often misdiagnosed
- no treatment
What is reduced glutathione?
- Tripeptide composed of 3 different amino acids
- Glutamate, cysteine and glycine
- Acts as scavenger for dangerous oxidative metabolites within cell
What does NADPH do in the red blood cell?
- Reduces glutathione
- Results in harmful peroxide converting to water
What is Glucose-6-phosphate dehydrogenase deficiency?
- Causes haemolytic anaemia
- RBC destroyed faster than bone marrow produces them
- X-linked recessive
- More common in people living in malaria-prevalent areas
- Changes G6PD shape making it not fully active
What is the role of G6PD in the cell?
- Maintains adequate levels of NADPH
- In RBC, NADPH responsible for reducing GSSG to GSH
- Without it RBC unable to neutralise peroxide (Strong oxidant) that will degrade RBC and cause haemolysis without reduction
- Can be found in oxidative drugs, fava beans
What is the clinical presentation of G6PD deficiency?
- Neonatal jaundice- insufficient activity in liver
- Haemolytic anaemia
- Oxidative stress
- Symptoms- fatigue, paleness, rapid heart rate, yellow skin, dark urine
What is haemolytic anaemia?
- Oxidative stress may result in denaturation of haemoglobin
- Results in loss of function and inability of RBC to effectively transport oxygen around body
- RBCs often prematurely destroyed
What does treatment for G6PD deficiency depend on?
- Discontinue oxidising drugs
- Change diet
- Blood transfusion
