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Vials

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In most tissues, 80-90% of all glucose oxidation is by glycolysis; the rest is ... Both F6P and GAP can enter glycolysis or gluconeogenesis ... – PowerPoint PPT presentation

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Title: 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

8
  • 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.

9
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

12
  • 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

21
  • 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

22
  • 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

26
R5P NADPH
R5P gt NADPH
NADPH, ATP, not R5P
NADPH gt R5P
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