Pentose Phosphate, Gluconeogenesis, Glycolysis and Krebs cycle

Pentose Phosphate
1. alternative route for glucose metabolism
  1. functions
    1. NADPH formation
      1. fatty acids and steroids synthesis
      2. maintenance of reduced glutathione for antioxidant activity
    2. ribose synthesis
      1. formation of nucleotides and nucleic acids
  2. reactions happens in the cytosol
    1. irreversible oxidative phase
      1. generates NADPH
      2. 1) dehydrogenation of glucose-6-phosphate to 6-phosphogluconate
        through 6-phosphogluconolactone formation
        hydrolyzed by the enzyme gluconolactone hydrolase
        catalyze by glucose-6-phosphate dehydrogenase
        NADP dependent enzyme
        2) catalysis by 6-phosphogluconate dehydrogenase
        requires NADP+ as hydrogen receptor
        decarbolixation
        Ribulose-5-phosphate
    2. reversible non-oxidative phase
      1. generates ribose precursors
      2. ribulose-5-phosphate
        substrate for two enzymes
        ribulose-5-phosphate 3-epimerase
        ribose-5-phosphate ketoisomerase
        ribose-5-phosphate
        can be synthesized in all tissues
        very little ribose circulates in the bloodstream
2. active in
  1. liver
  2. adipose tissue
  3. adrenal cortex
  4. thyroid
  5. red blood cells
  6. testicles
  7. lactating mammary glands
3. pathologies
  1. genetic defects of glucose-6-phosphate dehydrogenase
    1. deterioration of the NADPH generation
      1. hemolytic anemia
        when susceptible individuals are subjected to oxidative stress
Gluconeogenesis
1. depletion of glycogen reserves
2. reversal og glycolysis
3. takes place mainly in the liver and to a lesser extent in the renal cortex
4. 1) in the mitochondria
  1. pyruvate is carboxylated to form oxalacetate
    1. via the enzyme pyruvate carboxylase
      1. requires ATP and biotin as a coenzyme
5. 2) in the cytosol
  1. oxaloacetate is decarboxylated and rearranged to form phosphoenolpyruvate (PEP)
    1. via the enzyme PEP carboxykinase
      1. requires GTP and Mg+ as a cofactor
    2. 2-phosphoglycerate formation by hydration of PEP
      1. convertion to 3-phosphoglycerate
        3-phosphoglycerate phosphorilation to 1,3-bisphosphoglycerate.
        via the enzyme phosphoglycerate kinase
        requires ATP
        reduction to glyceraldehyde 3-phosphate
        NADH is the electron donor
        isomerization to form dihydroxyacetone phosphate
        form fructose 1,6-bisphosphate
        dephosphorilation to form fructose 6-phosphate
        convertion to glucose 6-phosphate
        dephosphorylation to form glucose
        by glucose 6-phosphatase
        free to enter the bloodstream
6. major substrates
  1. lactate
  2. glycerol
  3. glucogenic amino acids
    1. oxaloacetate
7. endorgenic
8. reactions can be regulated by
  1. glucagon
  2. insulin
    1. potent inhibitor of gluconeogenesis
9. function
  1. maintain glucose levels on blood during fast
10. pathologies
  1. hypoglycemia
    1. absence of glucose-6-phosphatase
    2. excess of lactate
  2. hyperglycemia
    1. excessive gluconeogénesis
      1. inadequate insulin production
      2. inability to respond to insulin properly
Glycolysis
1. main pathway of glucose metabolism
  1. happens in cytosol
    1. aerobic
      1. pyruvate goes to mitochondrias
        transforms in acetyl-CoA
        CO2 in krebs cycle
    2. anaerobic
      1. pyruvate
        reduces to lactate
        NADH oxidation
        another glucose molecule starts glycolysis
        red blood cells
        brain
        gastrointestinal tract
        renal marrow
        retina
        skin
  2. pathologies
    1. enzyme deficiency
      1. hemolytic anemia
      2. fatigue
        skeletal muscle
    2. thiamine deficiency
      1. reduction of pyruvate dehydrogenase activity
        lactic acidosis
2. glucose
  1. phosphorylation of glucose-6-phosphate
    1. hexokinase catalysis
      1. uses ATP as phosphate donor
    2. fructose-6-phosphate
      1. phosphohexose isomerase
      2. fructose 1,6-bisphosphate phosphorylation
        phosphofructokinase-1
        important in glycolysis speed regulation
        divided by aldolase
        dihydroxyacetone phosphate
        glyceraldehyde 3-phophate
        are inter-converted by triosephosphate isomerase
        oxidation to form 1,3-bisphosphoglycerate
        by glyceraldehyde 3-phosphate dehydrogenase
        NAD dependent
        3-phosphoglycerate
        by phosphoglycerate kinase
        forms 2 ATP
        2-phosphoglycerate
        dehydration to form phosphoenolpyruvate
        phosphorylation by pyruvate kinase
        forms pyruvate
        forms 2 ATP
Krebs cycle
1. reactions in mitochondrion
2. reaction between remaining acetyl-CoA and dicarboxylic acid oxaloacetate
  1. six-carbon citrate
    1. two CO2 molecules are released
      1. oxaloacetate regenerates
3. main pathway for the generation of ATP
4. acetyl-CoA + oxaloacetate
  1. catalyzed by citrate synthase
  2. forms citrate
    1. isomerization to isocitrate
      1. by aconitase enzyme
      2. isocitrate dehydrogenation to form
        isocyte dehydrogenase catalysis
        NAD+ dependent
        oxalosuccinate formation
        alphacetoglutarate decarboxylation
        requires Mg2+
        by alphacetoglutarate dehydrogenase complex
        requires thiamine diphosphate, NAD+, FAD
        succinyl-CoA formation
        succinate
        dehydrogenation to form fumarate
        by succinate dehydrogenase
        contains FAD
        production of malato
        oxidation of malate to oxalacetate
        by malate dehydrogenase
        reduction of NAD+
5. results in
  1. 3 NADH molecules
  2. FADH2 for every acetyl-CoA catalized molecule
  3. 10 ATP
6. involves in
  1. transamination and deamination
  2. aminoacid synthesis
  3. gluconeogenesis
  4. fatty acids synthesis

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Pentose Phosphate, Gluconeogenesis, Glycolysis and Krebs cycle

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	Created by Daiana Alexandra Rios Sandoval about 4 years ago