Hmp shunt
24
tose Phosphate Pathway 2-2-2013
description
For study purpose only.
Transcript of Hmp shunt
Pentose Phosphate Pathway
2-2-2013
Other names Definition Occurence & Tissue Distribution Biomedical Importance Metabolic Pathway Clinical Correlates Regulation Differences with EM Pathway References Acknowledgements
LaY Out
2-2-2013
Phosphogluconate Pathway
Pentose Cycle
Hexose Monophosphate Pathway or Shunt
Warburg-Dickens-Lipman Pathway
Other Names
2-2-2013
The process which brings about oxidation & decarboxylation at C-1 of Glucose 6-phosphate, reducing NADP+ to NADPH & producing Pentose Phosphates.
Definition
2-2-2013
IN CYTOSOL
Occurence
2-2-2013
LiverLactating Mammary Gland
Adrenal CortexGonads
Adipose TissueErythrocytes
Lens & Cornea
Tissue Distribution
2-2-2013
It has 2 main functions:Provides NADPHProvides PENTOSESThough there is oxidation of Glucose,but it is NOT meant for Energy.
BIOMEDICAL IMPORTANCE
2-2-2013
It has 2 Phases:1) Oxidative Phase2) Non-Oxidative Phase
Metabolic Pathway
2-2-2013
Glucose 6-Phosphate
Glucose 6-phosphate NADP+
Dehydrogenase Mg++ NADPH+H
6-phosphogluconolactone
6-phosphoglucolactonase H2O Mg++ H+
6-phosphogluconate
STAGE-1(Oxidative Phase)
2-2-2013
6-phosphogluconate6-phosphogluconate NADP+
Dehydrogenase Mg++ NADPH+H
3-Keto-6-phosphogluconate
D-Ribulose 5-phosphate + CO2
STAGE-1(continued)
2-2-2013
D-Ribulose 5-PhosphatePhosphopentose Isomerase
D-Ribose 5-phosphate
D-Ribose-1-P D-Ribose-1,5-di-P
STAGE-2(non-oxidative phase)a)INTERCONVERSION OF PENTOSES
2-2-2013
D-Ribulose-5-P Phosphopentose Epimerase
D-Xylulose-5-Phosphate
STAGE-2 (continued)
2-2-2013
2 Particular Enzymes are required:1)TRANSKETOLASE
2)TRANSALDOLASE
STAGE-2(continued)b)CONVERSION OF PP TO HEXOSE PHOSPHATES:
2-2-2013
1) Xylulose-5-P+Ribose-5-P Transketolase TPP
Sedoheptolose 7-Phosphate +
Glyceraldehyde-3-Phosphate
TRANSKETOLATION:
2-2-2013
Sedoheptolose 7-P+G3PTransaldolase
Fructose 6-Phosphate + Erythrose 4-Phosphate
TRANSALDOLATION:
2-2-2013
2)Xylulose 5-P+Erythrose 4-P Transketolase TPP
Fructose 6-Phosphate +G3P Dihydroxy-acetone-P+G3P
Recycles Fructose-1,6-bi-P
the Pathway Glucose-6-P Fructose-6-P
TRANSKETOLATION:
2-2-2013
G-6-PD deficiency results in:Heamolytic Aneamia
Neonatal Jaundice
Kidney failure
CLINICAL CORRELATES
2-2-2013
Mutation in gene coding for G6PD, production of NADPH decreases,low level of reduced glutathione---accumulation of H2O2---RBC’s memb. bursts---Heamolysis.Oxidant group of drugs e.g,
Antimalarials,Analgesics,Antipyretics & Sulpha antibiotics.
Fava beans.
CAUSES OF HEAMOLYSIS
2-2-2013
Genetically variant form of Transketolase. It can’t bind TPP, affecting “transketolation” reaction.
Symptoms are:Mental disordersSevere memory lossPartial paralysis
Wernicke-Korsakoff syndrome
2-2-2013
Results in:Liver cirrhosis
Male infertility
Deficiency of Transaldose
2-2-2013
Occurs in 3 ways:a) Ratio of [NADP+]\[NADPH]_1st Step is Rate-limiting step catalysed by G6PD.
b) Increased HMP Shunt on feeding high CHO diet & decreased in Diabetes Mellitusc)HORMONES: Insulin & Thyroid hormones
REGULATION:
2-2-2013
Differences with EM Pathway
EM PATHWAY HM PATHWAY
Occurs in all tissuesNot a multi cyclic
processNAD+ is H+
acceptorATP productionCO2 is never formed
Occurs in certain special tissues
Multi cyclic process NADP+ is H+
acceptorATP is not
producedCO2 is produced
2-2-2013
Lehninger Principles of Biochemistry5th edition,Pg.no 558-563Biochemistry by Thomas M.Devlin7th edition,Pg.no 648-652Harper’s Illustrated Biochemistry 29th
edition,Pg.no 197-204Medical Biochemistry by MN.Chatterjea
8th edition,Pg.no 354-360
REFERENCES
2-2-2013
2-2-2013
THANKYOU
