PENTOSE PHOSPHATE PATHWAY (PW:0000045)
Description
The pentose phosphate pathway (PPP), also known as the pentose phosphate shunt, represents an alternate route of glucose oxidation. The major route of glucose oxidation in many tissues is via glycolysis. However, 10-20% of glucose will be oxidized via the PPP and this percentage may be higher in tissues involved in lipid biosynthesis. The pathway consists of an oxidative and a non-oxidative phase. The oxidative phase is a series of three irreversible reactions that produce the reducing equivalent NADPH and the pentose Ru5P. NADPH is required for the reductive biosynthesis of fatty acids and cholesterol, cellular antioxidation (reduction of glutathione from its oxidized form by glutathione reductase) and superoxide generation (substrate of NADPH oxidase). Ru5P is epimerized to Xu5P or isomerized to R5P by the action of Rpe and Rpia, respectively. R5P is a precursor for nucleotide and nucleic acid synthesis. If the need for NADPH exceeds the need for R5P, Xu5P and R5P are formed in a ratio of 2:1 and metabolized to GAP and F6P via three reversible reactions involving carbon-carbon cleavage and transfer of C
2 and C
3 units. GAP and F6P are intermediates in the glycolytic and gluconeogenic pathway; they can be diverted back to R5P in the reverse reactions of the non-oxidative phase if the need for R5P increases (note the directionality of arrows). In the first and rate-limiting step of the oxidative phase, G6P is dehydrogenated by G6pd to produce the first NADPH and 6-phosphogluconolactone which is rapidly and irreversibly hydrolyzed to 6-phosphoglucone. This product is oxidatively decarboxylated to yield the second NADPH and Ru5P. The second and third reactions of the oxidative phase are carried out by Pgls and Pgd, respectively. The first reaction of the non-oxidative phase involves the conversion of Ru5P to Xy5P and R5P. If the non-oxidative phase proceeds, transketolase catalyzes the transfer of a C
2 unit from Xu5P to R5P yielding GAP and S7P. A C
3 unit is transferred from S7P to GAP in the reaction catalyzed by transaldolase to yield E4P and F6P. A C
2 unit is transferred from a second Xu5P to E4P to yield GAP and a second F6P molecule, a reaction also catalyzed by transketolase. Transketolase uses thiamine pyrophosphate as a co-factor. The carbon-carbon rearrangements underlie the pentose (Ru5P) to hexose (F6P) transformation. Despite the importance of the PPP in a number of cellular processes and its position at the crossroads of many metabolic pathways, little is known about how the pathway is regulated. Alterations in PPP components have been linked to several conditions.
To see the ontology report for annotations, GViewer and download, click here [Click here to see the ontology report for associated GO term - GO:0006098 , KEGG map -
map00030 and entry at
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Pathway Diagram:
Genes in Pathway:
G
Aldoa
aldolase, fructose-bisphosphate A
IEA ISO
KEGG SMPDB SMP:00031 rno:00030
NCBI chr 1:190,832,820...190,838,021
G
Aldoart2
aldolase 1 A retrogene 2
ISO
SMPDB SMP:00031
NCBI chr 6:78,674,945...78,676,635
G
Aldob
aldolase, fructose-bisphosphate B
IEA
KEGG rno:00030
NCBI chr 5:68,684,541...68,697,582
G
Aldoc
aldolase, fructose-bisphosphate C
IEA
KEGG rno:00030
NCBI chr10:63,715,544...63,719,133
G
Dera
deoxyribose-phosphate aldolase
ISO
SMPDB SMP:00031
NCBI chr 4:172,394,971...172,473,746
G
Fbp1
fructose-bisphosphatase 1
IEA ISO
KEGG SMPDB SMP:00031 rno:00030
NCBI chr17:2,212,941...2,235,749
G
Fbp2
fructose-bisphosphatase 2
IEA
KEGG rno:00030
NCBI chr17:2,241,767...2,259,371
G
G6pd
glucose-6-phosphate dehydrogenase
IEA ISO IDA
KEGG SMPDB PMID:2843500 SMP:00031 rno:00030, RGD:1599574
NCBI chr X:157,352,364...157,372,144
G
Gpi
glucose-6-phosphate isomerase
IEA ISO
KEGG SMPDB SMP:00031 rno:00030
NCBI chr 1:95,965,389...95,996,932
G
H6pd
hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase)
IEA
KEGG rno:00030
NCBI chr 5:165,717,456...165,753,158
G
Pfkl
phosphofructokinase, liver type
IEA ISO
KEGG SMPDB SMP:00031 rno:00030
NCBI chr20:10,663,907...10,685,967
G
Pfkm
phosphofructokinase, muscle
IEA
KEGG rno:00030
NCBI chr 7:131,100,684...131,138,250
G
Pfkp
phosphofructokinase, platelet
IEA
KEGG rno:00030
NCBI chr17:68,639,749...68,704,055
G
Pgd
phosphogluconate dehydrogenase
IDA ISO
SMPDB PMID:2843500 SMP:00031, RGD:1599574
NCBI chr 5:164,865,830...164,882,029
G
Pgls
6-phosphogluconolactonase
IEA ISO
KEGG SMPDB SMP:00031 rno:00030
NCBI chr16:18,334,299...18,339,785
G
Pgm1
phosphoglucomutase 1
IEA ISO
KEGG SMPDB SMP:00031 rno:00030
NCBI chr 5:119,710,734...119,770,159
G
Prps1
phosphoribosyl pyrophosphate synthetase 1
IEA
KEGG rno:00030
NCBI chr X:108,920,663...108,942,713
G
Prps1l1
phosphoribosyl pyrophosphate synthetase 1-like 1
IEA ISO
KEGG SMPDB SMP:00031 rno:00030
NCBI chr 6:57,412,331...57,414,021
G
Prps2
phosphoribosyl pyrophosphate synthetase 2
IEA
KEGG rno:00030
NCBI chr X:30,592,845...30,630,127
G
Rbks
ribokinase
IEA ISO
KEGG SMPDB SMP:00031 rno:00030
NCBI chr 6:30,467,724...30,544,284
G
Rgn
regucalcin
IEA
KEGG rno:00030
NCBI chr X:4,172,537...4,190,112
G
Rpe
ribulose-5-phosphate-3-epimerase
IDA ISO IEA
SMPDB KEGG PMID:2843500 SMP:00031 rno:00030, RGD:1599574
NCBI chr 9:75,640,867...75,661,009
G
Rpia
ribose 5-phosphate isomerase A
IDA ISO IEA
SMPDB KEGG PMID:2843500 SMP:00031 rno:00030, RGD:1599574
NCBI chr 4:104,282,081...104,307,732
G
Taldo1
transaldolase 1
IEA ISO IDA
KEGG SMPDB PMID:2843500 SMP:00031 rno:00030, RGD:1599574
NCBI chr 1:205,923,196...205,933,526
G
Tkt
transketolase
IEA ISO IDA
KEGG SMPDB PMID:2843500 SMP:00031 rno:00030, RGD:1599574
NCBI chr16:5,729,381...5,755,170
G
Tktl1
transketolase-like 1
IEA
KEGG rno:00030
NCBI chr X:157,105,455...157,138,510
G
Tktl2
transketolase-like 2
IEA
KEGG rno:00030
NCBI chr16:27,969,009...27,976,353
G
Rpe
ribulose-5-phosphate-3-epimerase
TAS
RGD
PMID:12721358 RGD:1641814
NCBI chr 9:75,640,867...75,661,009
G
Rpia
ribose 5-phosphate isomerase A
TAS
RGD
PMID:12721358 RGD:1641814
NCBI chr 4:104,282,081...104,307,732
G
Taldo1
transaldolase 1
IDA TAS
RGD
PMID:8477719 PMID:12721358 RGD:1641803 , RGD:1641814
NCBI chr 1:205,923,196...205,933,526
G
Tkt
transketolase
TAS IDA
RGD
PMID:9924800 PMID:16116031 PMID:12721358 RGD:1641798 , RGD:1580394 , RGD:1641814
NCBI chr16:5,729,381...5,755,170
G
G6pd
glucose-6-phosphate dehydrogenase
ISO
RGD
PMID:15466941 RGD:1625539
NCBI chr X:157,352,364...157,372,144
G
Pgd
phosphogluconate dehydrogenase
ISO
RGD
PMID:15466941 RGD:1625539
NCBI chr 5:164,865,830...164,882,029
G
Pgls
6-phosphogluconolactonase
IDA
RGD
PMID:971315 RGD:2311501
NCBI chr16:18,334,299...18,339,785
Pathway Gene Annotations
Disease Annotations Associated with Genes in the pentose phosphate pathway
Aldoa autistic disorder , Breast Neoplasms , cystadenoma , Endotoxemia , Glycogen Storage Disease XII , hereditary fructose intolerance syndrome , lung adenocarcinoma , Metabolic Syndrome , Myocardial Ischemia , Neoplasm Invasiveness , Neoplasm Metastasis , Reperfusion Injury , spondylocostal dysostosis 5 Aldoart2 cystadenoma , spondylocostal dysostosis 5 Aldob autoimmune hepatitis , Chemical and Drug Induced Liver Injury , diabetes mellitus , Experimental Diabetes Mellitus , fructose-1,6-bisphosphatase deficiency , genetic disease , hereditary fructose intolerance syndrome , Hypoxia , liver benign neoplasm , peritonitis , Stomach Neoplasms , type 2 diabetes mellitus Aldoc autoimmune disease of the nervous system , borna disease , hepatocellular carcinoma , stroke Dera COVID-19 Fbp1 Acute Liver Failure , Colonic Neoplasms , fructose-1,6-bisphosphatase deficiency , genetic disease , hepatocellular carcinoma , Parkinson's disease , schizophrenia , Stomach Neoplasms Fbp2 Acute Liver Failure , Childhood-Onset Remitting Leukodystrophy , Neurodevelopmental Disorders G6pd acute kidney failure , ALAD-Deficiency Porphyria , anemia , Brain Injuries , cataract , cerebrovascular disease , Chemical and Drug Induced Liver Injury , cholestasis , chronic granulomatous disease , congenital hemolytic anemia , congenital hypothyroidism , congenital nonspherocytic hemolytic anemia , congenital nonspherocytic hemolytic anemia 1 , contact dermatitis , diabetes mellitus , Diabetic Nephropathies , Experimental Diabetes Mellitus , favism , Fever , genetic disease , glucosephosphate dehydrogenase deficiency , Hemolysis , hemolytic anemia , hepatic encephalopathy , hepatocellular carcinoma , Hypercholesterolemia , hyperhomocysteinemia , Hypertriglyceridemia , immunodeficiency 14 , Insulin Resistance , kidney disease , Kidney Reperfusion Injury , Liver Injury , malaria , metabolic dysfunction-associated steatotic liver disease , Metabolic Syndrome , metachromatic leukodystrophy , Multi-Infarct Dementia , myocardial infarction , Neonatal Hyperbilirubinemia , neonatal jaundice , obesity , phagocyte bactericidal dysfunction , phenylketonuria , Plasmodium falciparum malaria , Pulmonary Hypertension, Hypoxia-Induced , renovascular hypertension , Testicular Injury , transient cerebral ischemia , type 1 diabetes mellitus , type 2 diabetes mellitus Gpi acute lymphoblastic leukemia , acute myeloid leukemia , Animal Disease Models , Breast Neoplasms , congenital hemolytic anemia , congenital nonspherocytic hemolytic anemia , congenital nonspherocytic hemolytic anemia 4 , Experimental Arthritis , genetic disease , hemolytic anemia , hereditary spherocytosis , intellectual disability , lung adenocarcinoma , Mental Retardation, Autosomal Recessive 42 , Neoplasm Metastasis , neuromuscular disease H6pd Breast Neoplasms , cortisone reductase deficiency , cortisone reductase deficiency 1 , Experimental Diabetes Mellitus , genetic disease , multiple sclerosis Pfkl hemolytic anemia Pfkm Experimental Diabetes Mellitus , genetic disease , glycogen storage disease , glycogen storage disease IV , glycogen storage disease VII , Myocardial Ischemia , peroxisome biogenesis disorder 3B , Rhabdomyolysis Pfkp Experimental Liver Cirrhosis , syndromic microphthalmia 5 Pgd COVID-19 , hepatocellular carcinoma Pgls osteoporosis Pgm1 Chemical and Drug Induced Liver Injury , Colorectal Neoplasms , congenital disorder of glycosylation , congenital disorder of glycosylation It , endometrial cancer , genetic disease , Myocardial Ischemia , teratoma Prps1 Arts syndrome , Charcot-Marie-Tooth disease type X , Charcot-Marie-Tooth disease X-linked recessive 5 , Developmental Disabilities , familial hypocalciuric hypercalcemia , fundus dystrophy , genetic disease , gout , Hearing Loss , Neurologic Manifestations , phosphoribosylpyrophosphate synthetase superactivity , retinitis pigmentosa , retinitis pigmentosa 1 , Weight Gain , X-linked deafness 1 Rgn Chemical and Drug Induced Liver Injury , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Experimental Liver Neoplasms , familial hyperlipidemia , hepatocellular carcinoma , kidney disease , liver cirrhosis , neurodegenerative disease , stomach cancer Rpia genetic disease , Ribose 5-Phosphate Isomerase Deficiency Taldo1 carbohydrate metabolic disorder , cataract , Chemical and Drug Induced Liver Injury , genetic disease , hepatocellular carcinoma , Parkinson's disease , Transaldolase Deficiency Tkt Animal Mammary Neoplasms , carcinoma , Experimental Mammary Neoplasms , Hypoxia , Neoplasm Invasiveness , Short Stature, Developmental Delay, and Congenital Heart Defects , Wernicke encephalopathy
acute kidney failure G6pd Acute Liver Failure Fbp1 , Fbp2 acute lymphoblastic leukemia Gpi acute myeloid leukemia Gpi ALAD-Deficiency Porphyria G6pd anemia G6pd Animal Disease Models Gpi Animal Mammary Neoplasms Tkt Arts syndrome Prps1 autistic disorder Aldoa autoimmune disease of the nervous system Aldoc autoimmune hepatitis Aldob borna disease Aldoc Brain Injuries G6pd Breast Neoplasms Aldoa , Gpi , H6pd carbohydrate metabolic disorder Taldo1 carcinoma Tkt cataract G6pd , Taldo1 cerebrovascular disease G6pd Charcot-Marie-Tooth disease type X Prps1 Charcot-Marie-Tooth disease X-linked recessive 5 Prps1 Chemical and Drug Induced Liver Injury Aldob , G6pd , Pgm1 , Rgn , Taldo1 Childhood-Onset Remitting Leukodystrophy Fbp2 cholestasis G6pd chronic granulomatous disease G6pd Colonic Neoplasms Fbp1 Colorectal Neoplasms Pgm1 congenital disorder of glycosylation Pgm1 congenital disorder of glycosylation It Pgm1 congenital hemolytic anemia G6pd , Gpi congenital hypothyroidism G6pd congenital nonspherocytic hemolytic anemia G6pd , Gpi congenital nonspherocytic hemolytic anemia 1 G6pd congenital nonspherocytic hemolytic anemia 4 Gpi contact dermatitis G6pd cortisone reductase deficiency H6pd cortisone reductase deficiency 1 H6pd COVID-19 Dera , Pgd cystadenoma Aldoa , Aldoart2 Developmental Disabilities Prps1 diabetes mellitus Aldob , G6pd Diabetic Nephropathies G6pd endometrial cancer Pgm1 Endotoxemia Aldoa Experimental Arthritis Gpi Experimental Diabetes Mellitus Aldob , G6pd , H6pd , Pfkm , Rgn Experimental Liver Cirrhosis Pfkp , Rgn Experimental Liver Neoplasms Rgn Experimental Mammary Neoplasms Tkt familial hyperlipidemia Rgn familial hypocalciuric hypercalcemia Prps1 favism G6pd Fever G6pd fructose-1,6-bisphosphatase deficiency Aldob , Fbp1 fundus dystrophy Prps1 genetic disease Aldob , Fbp1 , G6pd , Gpi , H6pd , Pfkm , Pgm1 , Prps1 , Rpia , Taldo1 glucosephosphate dehydrogenase deficiency G6pd glycogen storage disease Pfkm glycogen storage disease IV Pfkm glycogen storage disease VII Pfkm Glycogen Storage Disease XII Aldoa gout Prps1 Hearing Loss Prps1 Hemolysis G6pd hemolytic anemia G6pd , Gpi , Pfkl hepatic encephalopathy G6pd hepatocellular carcinoma Aldoc , Fbp1 , G6pd , Pgd , Rgn , Taldo1 hereditary fructose intolerance syndrome Aldoa , Aldob hereditary spherocytosis Gpi Hypercholesterolemia G6pd hyperhomocysteinemia G6pd Hypertriglyceridemia G6pd Hypoxia Aldob , Tkt immunodeficiency 14 G6pd Insulin Resistance G6pd intellectual disability Gpi kidney disease G6pd , Rgn Kidney Reperfusion Injury G6pd liver benign neoplasm Aldob liver cirrhosis Rgn Liver Injury G6pd lung adenocarcinoma Aldoa , Gpi malaria G6pd Mental Retardation, Autosomal Recessive 42 Gpi metabolic dysfunction-associated steatotic liver disease G6pd Metabolic Syndrome Aldoa , G6pd metachromatic leukodystrophy G6pd Multi-Infarct Dementia G6pd multiple sclerosis H6pd myocardial infarction G6pd Myocardial Ischemia Aldoa , Pfkm , Pgm1 Neonatal Hyperbilirubinemia G6pd neonatal jaundice G6pd Neoplasm Invasiveness Aldoa , Tkt Neoplasm Metastasis Aldoa , Gpi neurodegenerative disease Rgn Neurodevelopmental Disorders Fbp2 Neurologic Manifestations Prps1 neuromuscular disease Gpi obesity G6pd osteoporosis Pgls Parkinson's disease Fbp1 , Taldo1 peritonitis Aldob peroxisome biogenesis disorder 3B Pfkm phagocyte bactericidal dysfunction G6pd phenylketonuria G6pd phosphoribosylpyrophosphate synthetase superactivity Prps1 Plasmodium falciparum malaria G6pd Pulmonary Hypertension, Hypoxia-Induced G6pd renovascular hypertension G6pd Reperfusion Injury Aldoa retinitis pigmentosa Prps1 retinitis pigmentosa 1 Prps1 Rhabdomyolysis Pfkm Ribose 5-Phosphate Isomerase Deficiency Rpia schizophrenia Fbp1 Short Stature, Developmental Delay, and Congenital Heart Defects Tkt spondylocostal dysostosis 5 Aldoa , Aldoart2 stomach cancer Rgn Stomach Neoplasms Aldob , Fbp1 stroke Aldoc syndromic microphthalmia 5 Pfkp teratoma Pgm1 Testicular Injury G6pd Transaldolase Deficiency Taldo1 transient cerebral ischemia G6pd type 1 diabetes mellitus G6pd type 2 diabetes mellitus Aldob , G6pd Weight Gain Prps1 Wernicke encephalopathy Tkt X-linked deafness 1 Prps1
