MT201 CH14 glycolysis

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MT201 CH14 glycolysis Powered By Docstoc
					Eduard Buchner
(1860-1917)
1897 found fermentation in
broken yeast cells
1907 Nobel Prize in Chemistry
The whole pathway in yeast and
muscle cell were elucidated by


     Arthur Harden
     1865-1940
                Glycolysis
• Glycolysis is an almost universal central
  pathway of glucose catabolism, the pathway
  with the largest flux of carbon in most cells.
• In some mammalian tissues (erythrocytes,
  renal medulla, brain, sperm), the glycolytic
  breakdown of glucose is the sole source of
  metabolic energy.
               Glycolysis
• Some of the starch-storing tissues, like
  potato tubers, and some aquatic plants
  derive most of their energy from glycolysis.
• Many anaerobic microorganisms are
  entirely dependent on glycolysis.
1. phosphorylation of glucose
2. Isomerization of glucose 6-
          phosphate
  Phosphohexose isomerase reaction




          by an active-site His residue


Glu
 3. Phosphorylation of fructose 6-
phosphate: the first committed step
           in glycolysis
PFK-1 is named so because there
 is another enzyme catalyzes a
        similar reaction
In some bacteria, protists and (all) plants,
a pyrophosphate-dependent
phosphofructokinase (PFP) also
catalyzes this reaction in a reversible
way
4. Cleavage of fructose 1,6-
       bisphosphate
     Class I aldolases form Schiff base
intermediate during sugar cleavage reaction


                        • Class I aldolases were
                          found in animals and
                          plants.
                        • Class II aldolases
                          (fungi and bacteria) do
                          not form the Schiff
                          base and require a zinc
                          ion to catalyze
                          reaction.
5. Interconversion of the triose
           phosphate
   Dihydroxyacetone phosphate and
 glyceraldehyde 3-phosphate become
indistinguishable after triose phosphate
          isomerase reaction
  6. Oxidation of glyceraldehyde 3-
phosphate to 1,3-bisphosphoglycerate
       The glyceraldehyde 3-phosphate
           dehydrogenase reaction


Heavy metal ion
such as Hg2+ will
react with Cys
residue, hence
irreversibly
inhibits the          hemiacetal
enzyme.
7. Phosphoryl transfer from 1,3-
  bisphosphoglycerate to ADP
      Glyceraldehyde 3-phosphate
  dehydrogenase and Phosphoglycerate
       kinase are coupled in vivo
• Glyceraldehyde 3-phosphate dehydrogenase
  catalyzes an endergonic reaction while
  phosphoglycerate kinase catalyzes an
  exergonic reaction.
• When these two reactions are coupled
  (which happens in vivo), the overall reaction
  is exergonic.
The formation of ATP by phosphoryl group
 transfer from a substrate is referred to as a
       substrate-level phosphorylation

Substrate-level phosphorylation
     soluble enzymes
     chemical intermediates


Respiration-linked phosphorylation
Photophosphorylation
     membrane-bound enzymes
     transmembrane gradients of protons
 8. Conversion of 3-
phosphoglycerate to 2-
  phosphoglycerate
The phosphoglycerate mutase
         reaction
2,3-Bisphosphoglycerate (BPG)
               • The concentration of
                 BPG is usually low in
                 most of the tissues
                 except erythrocytes
                 (up to 5 mM).
               • Function of BPG in
                 erythrocytes is to
                 regulate the affinity of
                 hemoglobulin to O2.
9. Dehydration of 2-
 phosphoglycerate to
phosphoenolpyruvate
 10. Transfer of the phosphoryl
group from phosphoenolpyruvate
            to ADP
Glucose + 2ATP + 2NAD+ + 4ADP + 2Pi 
    2 pyruvate + 2ADP + 2NADH + 2H+ +
4ATP + 2H2O

Glucose + 2ADP + 2NAD+ + 2Pi 
    2 pyruvate + 2ATP + 2NADH + 2H+

在有氧狀況下,產生的NADH很快就被送
到mitochondria中用來合成ATP
  NAD+ (nicotinamide adenine
dinucleotide) is the active form of
              niacin
Niacin
   • Niacin is the common
     name for nicotinamide
     and nicotinic acid.
   • Nicotinic acid is the
     common precursor for
     NAD+ and NADP+
     biosynthesis in cytosol.
 Functions of   NAD+    and   NADP+


• Both NAD+ and NADP+ are coenzymes for
  many dehydrogenases in cytosol and
  mitochondria
• NAD+ is involved in oxidoreduction
  reactions in oxidative pathways.
• NADP+ is involved mostly in reductive
  biosynthesis.
 Niacin deficiency: pellagra




Weight loss, digestive disorders, dermatitis, dementia
            Niacin deficiency
• Because niacin is present in most of the food and
  NAD+ can also be produced from tryptophan (60
  grams of trptophan  1 gram of NAD+), so it is
  not often to observe niacin deficiency.
• However, niacin deficiency can still be observed
  in areas where maize is the main carbohydrate
  source because maize only contain niacytin, a
  bound unavailable form of niacin. Pre-treated
  maize with base will release the niacin from
  niacytin.
            Niacin deficiency
• Areas where sorghum is the main carbohydrate
  source will also observe niacin deficiency if niacin
  uptake is not being watched carefully.
• Sorghum contains large amount of leucine, which
  will inhibit quinolinate phosphoribosyl transferase
  (QPRT), an enzyme involved in NAD+
  biosynthesis from tryptophan.
• Vitamin B6 deficiency can also lead to niacin
  deficiency because pyridoxal phosphate is a
  coenzyme in NAD+ biosynthesis from tryptophan.
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Feeder pathways for glycolysis
     Glycogen and starch are
   degraded by phosphorolysis
• Glycogen and starch can be mobilized for
  use by a phosphorolytic reaction catalyzed
  by glycogen/starch phosphorylase. This
  enzyme catalyze an attack by Pi on the
  (a14) glycosidic linkage from the
  nonreducing end, generating glucose 1-
  phosphate and a polymer one glucose unit
  shorter.
Branch point (a16) is removed
    by debranching enzyme
Glucose 1-phosphate is converted to G-6-P by
phosphoglucomutase by the same mechanism
observed in phosphoglycerate mutase reaction
          Digestion of dietary
           polysaccharides
• Digestion begins in the mouth with salivary a-
  amylase hydrolyze (attacking by water) the
  internal glycosidic linkages.
• Salivary a-amylase is then inactivated by gastric
  juice; however pancreatic a-amylase will take its
  place at small intestine.
• The products are maltose, maltotriose, and limit
  dextrins (fragments of amylopectin containing
  a16 branch points.
         Digestion of dietary
            disaccharides
• Disaccharides must be hydrolyzed to
  monosaccharides before entering cells.
• Dextrin + nH2O  n D-glucose
                dextrinase
• Maltose + H2O  2 D-glucose
                maltase
                 
• Lactose + H2OlactaseD-galactose + D-glucose
• Sucrose + H2O  D-fructose + D-glucose
               sucrase
• Trehalose + H2O  2 D-glucose
                  trehalase
           Lactose intolerance




• Lactose intolerance is due to the disappearance
  after childhood of most or all of the lactase
  activity of the intestinal cells.
Lactose intolerance
          • Undigested lactose
            will be converted to
            toxic products by
            bacteria in large
            intestine, causing
            abdominal cramps and
            diarrhea.
Fructose metabolism in muscle
         and kidney
    Fructose metabolism in liver


                                               Triose
                                               phosphate
                                               isomerase




• In liver, the enzyme fructokinase
  catalyze the phosphorylation of fructose to form
  fructose 1-phosphate.
         Galactose metabolism




• Galactose is phosphorylated by galactokinase in
  the liver.
• Then galactose 1-phosphate is converted to
  glucose 1-phosphate by a series of reactions.
Galactose metabolism

 • The conversion of galactose
   1-P to glucose 1-P
   (epimerization) requires
   uridine diphosphate (UDP)
   as a coenzyme-like carrier of
   hexose groups.
              Galactosemia
inability to metabolize galactose due to lack
  of
  1. UDP-glucose galactose 1-phosphate
  uridylyltransferase (classical galactosemia)
  2. UDP-glucose 4-epimerase
  3. Galactokinase
Among these, deficiency of either 1 or 2 is
  more severe (1 is the most severe).
Galactosemia
      • Deficiency of
        transferase (or
        epimerase) will result
        in poor growth, speech
        abnormality, mental
        deficiency, and (fatal)
        liver damage even
        when galactose is
        withheld from the diet.
Galactosemia patients develop cataracts
 by deposition of galactitol in the lens
         Mannose metabolism


 Mannose + ATP  mannose 6-phosphate
             hexokinase          +ADP
mannose 6-phosphate  fructose 6-phosphate
            phosphomannose isomerase
             Fermentation
• Fermentation is referring to the process
  when no oxygen is consumed or no change
  in the concentration of NAD+ or NADH
  during energy extraction.
               Fermentation




• Under hypoxic conditions, oxidative
  phosphorylation will be the first to stop. Then
  citric acid cycle will come to a halt due to
  inhibition effect from NADH. As a result,
  glycolysis will be the only metabolic pathway that
  is available to energy production during hypoxia.
Fermenation
      • However, the
        oxidation of
        glyceraldehyde 3-
        phosphate consumes
        NAD+ that will not be
        regenerated under
        hypoxic condition
        because oxidative
        phosphorylation is not
        available.
The purpose of fermentation is to
       regenerate NAD+
                 • In order to continue
                   regenerating NAD+,
                   cells come up a
                   strategy.
                 • During fermentation,
                   NAD+ is regenerated
                   during the reduction of
                   pyruvate, the product
                   of glycolysis.
Lactate fermentation
                 glycolysis
Lactate is recycled in the liver
         (Cori cycle)
Carl and Gerty Cori, 1947 Nobel Prize in Physiology and
                       Medicine
Lactate fermentation only
happened in larger animals
             • Most small vertebrates
               and moderate size
               running animals have
               circulatory systems
               that can carry oxygen
               to their muscles fast
               enough to avoid
               having to use muscle
               glycogen
               anaerobically.
 http://www.mountain-research.org/CV/coelacanth.jpg

                                                      http://www.anac.8m.net/Images/coelacanth.jpg
Deep sea fish (below 4,000 m
or more) coelacanth uses
anaerobic metabolism
exclusively. The lactate
produced is excreted directly.
Some marine vertebrates can
do ethanol fermentation.
           Ethanol fermentation




• Yeast and other microorganisms ferment glucose to
  ethanol and CO2.
• Pyruvate is first decarboxylated by pyruvate decarboxylase,
  which is absent in vertebrate tissues and in other organisms
  that carry out lactic acid fermentation. Acetaldehyde is the
  product of this reaction.
Pyruvate decarboxylase
           • The decarboxylation
             of pyruvate by
             pyruvate
             decarboxylase
             produces CO2, which
             is the reason why
             champagne is
             bubbling.
  Thiamine pyrophosphate (TPP) is the
  coenzyme of pyruvate decarboxylase




• Thiamine pyrophosphate is derived from vitamin
  B1 (thiamine).
• Lack of vitamine B1 will lead to beriberi (edema,
  pain, paralysis, death).
TPP plays an important role in the cleavage of
    bonds adjacent to a carbonyl group.
                        • The thiazolium ring of
                          TPP acts as an
                          “electron sink” to
                          facilitates
                          decarboxylation
                          reaction.
Alcohol dehydrogenase catalyze the
second step of ethanol fermentation
                  • Alcohol
                    dehydrogeanse
                    reduces acetaldehyde,
                    producing NAD+ and
                    ethanol.
                  • This enzyme is present
                    in many organisms
                    that metabolize
                    ethanol, including
                    human.
Fermentation has commercial
           values
              • Bacteria like
                Lactobacillus
                bulgaricus (yogurt)
                and
                Propionibacterium
                freudenreichii (swiss
                cheese) ferments milk
                to produce lactic acid
                or propionic acid and
                CO2.
Dr. Chaim Weizmann
1874-1952
First President of Israel
Found butanol and acetone
fermentation in Clostridium acetobutyricum
Industrial fermentation is done in
         huge close vats
                 • Fermentors are huge
                   closed vats in which
                   temperature and access to
                   air are adjusted to favor
                   the multiplication of the
                   desired microorganism.
                 • Some even immobilize the
                   cells in an inert support so
                   no effort is required to
                   separate microorganisms
                   from products after
                   fermentation is completed.

				
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posted:6/21/2012
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