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2010-10-13 22:05:14
gluconeogenesis metabolism monosaccharides glycogen

Gluconeogenesis & metabolism of monosaccharides
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  1. definition of gluconeogenesis
    net synthesis of glucose from noncarbohydrate sources
  2. sites of gluconeognesis
    mostly liver; some in kidney; enzymes not expressed in all tissues
  3. enzymatic regulation of gluconeogenesis
    reciprocal regulation as compared to glycolysis; pyruvate -> oxaloacetic acid (pyruvate carboxylase - activated by acetyl CoA) ->PEP (PEP carboxykinase - in liver but not muscle; requires hydrolysis of GTP) -> fructose 1 6 bisphosphate -> fructose 6-phosphate (fructose 1 6 bisphosphatase; regulated by PFK-2) -> glucose 6-phosphate -> glucose (glucose 6-phosphatase; found only in liver)
  4. gluconeogenesis from amino acids
    alpha-ketoacids enter the citric acid cycle to form oxaloacetate -> PEP -> glucose
  5. gluconeogenesis from odd-number fatty acid chains
    oxidation of odd-number fatty acid chains ->intermediates -> succinyl CoA -> 0.5 glucose; uses 2 ATP
  6. gluconeogenesis from glycerol
    glycerol -> glycerol-3-phosphate (glycerol kinase = catalyst; uses ATP) -> dihydroxyacetone phosphoate (glycerol -3-phosphate dehydrogenase = catalyst; uses NADH) -> 1/2 glucose or lactate
  7. hormonal regulation of gluconeogenesis
    glucagon increases gluconeogenesis and decreases glycolysis; insulin decreases gluconeogenesis and increases glycolysis; regulation occurs @ level of F26BP (action of PFK-1 or FBPase-1)
  8. the Cori cycle
    supports glycolysis in tissues that lack mitochondria; release of lactate from exercising skeletal muscle/cells lacking mitochondria -> diffusion into blood -> uptake by liver -> conversion of lactate to glucose in liver -> re-release into bloodstream; net loss of 4 ATP from 2 lactate
  9. the alanine cycle
    supports glycolysis in tissues with partial oxygen deprivation; release of lactate from oxygen-deprived muscles -> liver -> glucose and urea; requires presence of alanine aminotransferase (found only in liver & muscle & intestine); transports ammonia to the liver; net loss of 3-5 ATP from 2 alanine
  10. purpose of glycogen storage
    mobilized more quickly than fat stores; can be metabolized without oxygen (unlike fat stores); difficult to make glucose for brain from fat; osmotic pressure issues with storge as glucose
  11. production of glycogen
    occurs in cytosol; requires ATP and UTP; steps = initiation; elongation; branching
  12. storage of glycogen in liver
    accounts for less total glycogen storage than muscles; about 10% of liver devoted to glycogen; glycogen maintains blood glucose levels to provides energy for other tissues
  13. storage of glycogen in muscles
    accounts for most total glycogen storage; about 1-2% of muscles devoted to glycogen; glycogen provides energy for muscles only
  14. glycogen storage diseases
    glucose-6-phosphatase deficiency in liver -> Von Gierke's (type I); alpha 1->4 glucosidase deficiency in lysosomes -> Pompe's (type II); muscle phosphorylase deficiency in muscle -> McArdle's (type V)
  15. pentose phosphate pathway
    provides building blocks for nucleic acid synthesis; occurs in cytosol in the absence of oxygen; involves two non-reversible steps; step 1: glucose-6-phosphate+ NADP+ -> 6-phosphogluconate + NADPH (via glucose-6-phosphate dehydrogenase); step 2: 6-phosphogluconate + NADP+ -> CO2 + ribose-5-phosphate + NADPH
  16. NADPH
    functions as a biological reductant
  17. structure of glycogen
    branched-chain homopolysaccharide made up of alpha D-glucose; primarily alpha (1->4) glycosidic bonds; branch with with alpha (1->6) glycosidic bonds every 8-10 glucosyl residues
  18. initiation of glycogen production
    UTP + glucose-1-phosphate ->UDP-glucose via action of UDP-glucose-phosphorylase; glycogenin or glycogen fragments act as primers by accepting glucose residues from UDP-glucose; glycogenin continues to catalyze addition of glucose residues until glycogen synthase takes over
  19. elongation step in glycogen production
    glycogen synthase catalyzes the transfer of glucose from UDP-glucose to the nonreducing end of the growing chain - forms bonds between C1 of the activated glucose and C4 of the accepting glycosyl residue
  20. branching step in glycogen production
    "branching increases solubility of glycogen and speeds up the processes of glycogen synthesis and degradation; ""branching enzyme"" breaks an alpha 1->4 bond and transfers a chain of 6 to 8 glucosyl residues to another residue; chain is attached by alpha 1->6 linkages"
  21. degradation of glycogen
    glycogen phosphorylase cleaves 1->4 bonds at nonreducing ends of glycogen chains until 4 residues remain on each chain before a branch point; 4-D-glucotransferase transfers 3 residues from a branch to the end of another chain; A 1->6 glucosidase removes the last remaining glucose
  22. stimulation of glycogen synthesis and degradation
    insulin -> stimulation of glycogen synthesis; glucagon & beta-agonists (no glucagon receptors in muscles) -> stimulation of cAMP-mediated glycogen degradation; alpha-agonists -> stimulation of IP3- and calcium-mediated glycogen degradation
  23. fructose
    fructose entry -> cells is not insulin-dependent; fructose does not raise glycemic index as much as sucrose; fructose is more efficiently converted to fat than sucrose and may contribute to insulin resistance/obesity
  24. metabolism of galactose
    galactose -> galactose-1-phosphate (via actions of galactokinase); galactose-1-phosphate + UDP-glucose -> glucose-1-phosphate + UPD-galactose (via galactose-1-phosphate uridylyl transferase); UDP-galactose recycled to UDP-glucose via UDP-galactose-4-epimerase; G1P -> G6P -> glycolysis
  25. metabolism of mannose
    mannose -> mannose-6-phosphate (via actions of hexokinase) -> fructose-6-kinase (via actions of phosphomannose isomerase) -> glycolysis
  26. metabolism of fructose in muscle
    fructose -> fructose-6-phosphate via actions of hexokinase -> glycolysis; hexokinase has low affinity for fructose and so is less important than the fructokinase-mediated pathway in the liver
  27. metabolism of fructose in liver
    fructose -> fructose-1-phosphate (via actions of fructokinase) -> glyceraldehyde (via actions of fructose-1-phosphate aldolase); glyceraldehyde can be phosphorylated by glyceraldehyde kinase to make glyceraldehyde-3-phosphate -> glycolysis; glyceraldehyde can also be converted to glycerol using alcohol dehydrogenase and from there can follow a number of pathways (-> phosphoglyceride synthesis; -> triacylglyceride synthesis; -> glycolysis)
  28. glucose 6-P dehydrogenase deficiency
    X-linked recessive hereditary disease; results in loss of NADPH production; increases oxidative stress & membrane damage & red blood cell lysis