Biochemistry Notes (Quiz #3)

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Harper’s: Pentose Phosphate Pathway & Other Pathways of Hexose Metabolism

Pentose Phosphate Pathway (summary)

 Alternative route for glucose metabolism

 Leads to:
o formation of NADPH (for fatty acid and steroid synthesis)
o maintaining reduced glutathione (antioxidant activity)
o ribose synthesis (for nucleotide and nucleic acid formation)

Biomedical importance

 Genetic deficiency of glucose-6-phosphate (G6P) dehydrogenase  acute hemolysis of RBC 

hemolytic anemia
 Glucuronic acid synthesized via uronic acid pathway  glucuronides (significant for conjugation
and excretion of metabolites and foreign chemicals)
o Deficiency in pathway  essential pentosuria
o Lack of gulonolactone oxidase in pathway explains why ascorbic acid is a dietary
requirement
 Deficiency of enzymes for fructose and galactose metabolism  essential fructosuria, hereditary
fructose intolerance, galactosemia

Pentose Phosphate Pathway

 aka hexose monophosphate shunt (HMP shunt)

 G6P IS BOTH THE SUBSTRATE AND END PRODUCT
 3 G6P molecules  3 CO2 + 3 5-carbon sugars (pentoses)  regeneration of 2 GP molecules + 1
glyceraldehyde-3-phosphate (G3P/GADP)
o 3 G6P  3 CO2 + 3 pentoses  2 G6P + 1 GADP
 Pentoses in pathway:
o Ribulose-5-phosphate
o Xylulose-5-phosphate
o Ribose-5-phosphate
 2 GADP can regenerate 1 G6P
 Reactions catalyzed by fructose 1,6-bisphosphatase are not freely reversible
 PPP occurs in cytosol
 NADP+ as hydrogen acceptor
 Two phases
o IRREVERSIBLE oxidative phase
 G6P  dehydrogenation and decarboxylation  ribulose-5-phosphate
o REVERSIBLE nonoxidative phase
  Ribulose-5-phosphate  G6P
 Enzymes involved: transketolase, transaldolase

Oxidative Phase of PPP

 Generates NADPH
 STEP 1: G6P  dehydrogenation  6-phosphogluconate
o ENZYME: glucose-6-phosphate dehydrogenase
 NADP-dependent
o Occurs via the formation of 6-phosphogluconolactate
 6-phosphogluconolactate  hydrolysis by gluconolactone hydrolase
 STEP 2: 6-phosphogluconate  decarboxylation  ribulose-5-phosphate
o ENZYME: 6-phosphogluconate dehydrogenase
 NADP+ as hydrogen acceptor
 Hexose-6-phosphate dehydrogenase
o Isoenzyme of G6P dehydrogenase
o Provides NADPH for hydroxylation and for 11-β-hydroxysteroid dehydrogenase-1
o Catalyzes reduction of inactive cortisone to active cortisol in the liver, nervous system,
adipose tissue
o MAJOR SOURCE OF INTRACELLULAR CORTISOL
 May be important in obesity and metabolic syndrome

Nonoxidative Phase of PPP

 Ribulose-5-phosphate is a substrate of TWO enzymes:

o Ribulose-5-phosphate 3-epimerase
 Alters configuration of ribulose’s C3  yields epimer Xylulose 5-phosphate
o Ribulose-5-phosphate ketoisomerase
 Converts to aldopentose  Ribose-5-phosphate (used for nucleotide and nucleic
acid synthesis)
 Transketolase