Vials

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• In most tissues, 80-90 of all glucose oxidation
  is by glycolysis the rest is pentose phosphate
  pathway.
• Glucose can enter this pathway after conversion
  to glucose 6-phosphate- important branch point
• 2nd pathway for glucose metabolism that leads to
  specialized products that the body needs

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• Some called Hexose monophosphate shunt or
  Phosphogluconate pathway
• Glucose used to generate NADPH
• NADH (universal reductant) in anaerobic pathways.
• Glucose enter this pathway after conversion to
  glucose-6-phosphate
• No ATP consumed or Generated

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• Generate NADPH
• Needed for synthesis of FFA and Steroid
• Similar to NAD- NADP has an extra phosphate
• In mammals, this pathway is prominent in tissues
  actively carrying out biosynthesis of FFA and
  Steroids from small precursors molecules- need
  NADPH

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• Generate NADPH (cont.)
• The needs of NADPH
• Prevalent in the mammary gland, adipose tissue,
  the adrenal cortex and the liver
• Other tissues (skeletal muscle, brain) have
  virtually no pentose phosphate activity.

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The pathways requiring NADPH
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• Generate Ribose 5-phosphate (R5P)
• For biosynthesis of nucleotides, nucleic acids
  and several enzymes cofactor
• Enzymes of the pathway are located in the cytosol
• The pathway is divided into an oxidative and
  non-oxidative branch
• The oxidative branch produces NADPH and ribose
  5-phosphate as G6P is oxidized

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• Generate Ribose 5-phosphate (R5P) (cont.)
• The pathway is divided into an oxidative and
  non-oxidative branch (cont.)
• In non-oxidative branch, depending on cellular
  conditions, the pentose phosphates are either
  converted to ribose-5-phosphate or converted to
  the glycolytic intermediates- fructose-6-phosphat
  e (F6P) and glyceraldehyde 3-phosphate (GAP)

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• Convert Pentose to Hexoses
• Feeding into glycolysis
• Convert dietary 5-C sugars into both 6-C sugar
  (F-6P) and 3-C sugar (G3P) which can be then
  utilized by the pathways of glycolysis

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• Major role of NADPH, in rbc, is to reduce the
  disulfide form of glutathione to sulfhydryl form.
  The reduced glutathione is pertinent for
  maintaining the normal structure of rbc and for
  keeping hemoglobin in the ferrous state (Fe2)
• Reduced glutathione is necessary for the removal
  of H2O2 and lipid peroxides
• People with G6PDH deficiency, radical species
  cause cellular damage since the NADPH production
  is diminished and detoxification is inhibited
• Erythrocyte membrane breakdown and subsequent
  rupture (hemolysis) results.
• Deficiency also leads to resistance to malarial
  parasite. (it cannot sustain the life cycle long
  enough for growth)

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• The oxidative phase of the PPP. G6P is oxidized
  to 3-phosphoglucono D-lactone to generate one
  molecule of NADPH. The lactone product is
  hydrolyzed to 6-phosphogluconate, which is
  oxidatively decarboxylated to ribulose
  5-phosphate with the generation of a second
  molecule of NADPH

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• The pathway catalyzes the interconversion of
  three-, four-, five-, size-, and seven-carbon
  sugars
• Results in the synthesis of 5-carbon sugars for
  nucleotide biosynthesis, or conversion of excess
  5-carbon sugars into intermediates of the
  glycolysis pathway
• The conversion reaction is catalyzed
  transketolase, and transaldolase
• All these reactions take place in the cytosol

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• The net result of these reactions is the
  formation of 2 hexoses and one triose from 3
  pentoses

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Phosphopentose isomerase

• Thus, excess ribose 5-phosphate formed by the PPP
  can be completed converted into glycolytic
  intermediates.
• Moreover, any ribose ingested in the diet can be
  processed into glycolytic intermediates by this
  pathway.

Transketolase
Transaldolase
Transketolase
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• Both F6P and GAP can enter glycolysis or
  gluconeogenesis

• Cytoplasmic NADP plays a
  key role in determining the fate of G6P
• The dehydrogenation of G6P is essentially
  irreversible
• The inhibitory effect of low levels of NADP is
  exacerbated by NADPH competes with NADP in
  binding to the enzyme

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R5P NADPH
R5P gt NADPH
NADPH, ATP, not R5P
NADPH gt R5P