Glucose metabolism Flashcards

1
Q

chemical digestion during digestion in humans (mouth, stomach, small and large intestine)

A
  1. mouth:
    - salivary amylases
    - lingual lipase
  2. stomach:
    - gastrin
    - gastrin lipases (chief cells)
    - HCl (periatal cells)
    - pepsin (chief cells)
  3. small intestine (some come from pancreatic)
    - trypsinogen
    - chymotrypsinogen
    - carboxypeptidase A and B
    - pancreatic amylae/lipase
    - active enzymes target specific AA in proteins
  4. large intestine: only mechanical digestion, no chemical
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2
Q

why glucose is a versatile precursors (precursor of what) (4)

A
  • all AA
  • membrane lipids
  • nucleotides in DNA and RNA
  • cofactors in metabolism
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3
Q

4 ways glucose can take + the product

A
  1. storage = glycogen/starch/sucrose
  2. oxidation via glycolysis= pyruvate
  3. oxidation via pentose phosphate pathway = ribose-5-phosphate
  4. synthesis of structural polymers= extracellular matrix and cell wall polysaccharides
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4
Q

definition glycolysis, gluconeogenesis, glycogenesis, glycogenolysis

A
  • glycolysis: glucose is degrade into pyruvate
  • gluconeogenesis: glucose is formed from non-carbohydrate source
  • glycogenesis: glucogen is polymerized from glucose units
  • glycogenolysis: glycogen is degraded to glucose units
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5
Q

glycolysis : step 1: phosphorylation of glucose

A
    • transforms glucose into glucose-6-phosphate
  • enzyme: hexokinase
  • traps glucose inside the cells
  • lowers intracellular (unphosphporylated) glucose to allow further uptake
  • require energy from ATP
  • irreversible
  • multiple isoforms of hexokinase
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6
Q

step 2: phosphohexose isomerization

A
  • glucose-6-phosphate to fructose-6-phosphate
  • enzyme: phosphohexose isomerase
  • makes next step easier:
  • C1 of fructose is easier to phosphorylate by PFK
  • allows for symmetrical cleavage by aldolase
  • reversible
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7
Q

step 3 : second priming phosphorylation

A

fructose-6-phosphate to fructose 1,6-biphosphate

  • enzyme: phosphofructokinase
    • C1 is phosphorylated so C1 and C6 are
  • generate a symmetric 6-carbon molecule
  • first committed step of glycolysis (it is irreversible, don’t have the choice to go through glycolysis)
  • uses the energy of ATP
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8
Q

step 4: Aldo cleavage of F-1,6-bP

A

fructose 1,6 biphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate

  • enzyme: aldolase
  • 6-carbone sugars cleaved into 3 carbons sugar
  • reversible
  • high-energy sugar phosphate
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9
Q

step 5: triose phosphate interconversion

A
  • dihydroxyacetone phosphate to glyceraldehyde 3-phosphate (GAP)
  • enzyme: triose phosphate isomerase
  • only GAP is the substrate for the next enzyme
  • reversible
    • end of the preparatory phase of glycolysis
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10
Q

step 6: oxidation of GAP

A
  • GAP to 1,3-biphosphoglycerate
  • enzyme: glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
  • first-energy rich molecule: oxidation of GAP with NAD+ gives NADH
  • incorporates inorganic phosphate
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11
Q

step 7: 1st production of ATP

A
  • 1,3 biphosphoglycerate to 3-phosphoglycerate
  • enzyme: phosphoglycerate kinase (require Mg2+ to function)
    substrate level phosphorylation
  • quick source of ATP
  • 1,3-biphosphoglycerate gives its P to ADP to form ATP
  • reversible
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12
Q

step 8: migration of the phosphate

A
  • 3-phosphoglycerate to 2-phosphoglycerate
  • enzyme: phosphoglycerate mutase
  • mutase catalyze the migration of functional groups
  • phosphohistidine of the enzyme donates its phosphate to 3-phosphoglycerate at the 2-carbon before retrieving phosphate from the 3C (so there is a small moment where the enzyme is inactive)
  • reversible
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13
Q

step 9 : dehydration of 2-PG to PEP

A
    • 2-phosphoglycerate to phosphoenolpyruvate
  • enzyme: enolase
  • generate a high-energy phosphate compund (because of the double bond)
  • reversible
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14
Q

step 10: 2nd production of ATP

A
    • PEP to pyruvate
  • enzyme: pyruvate kinase
  • substrate level phosphorylation
  • pyruvate kinase requires metal ions for activity (Mg2+, K+)
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15
Q

enzyme converted pyruvate to lactase

A

lactase dehydrogenase

** NAD+ is generated

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16
Q

what happens during normoxia (normal amount of oxygen) and hypoxia (not enough)

A
  • PHD2 (prolyl hydrolase) is a protein that sense oxygen tension
  • HIF (hypoxia inducible factor)
    1. normoxia:
    PHD2 induces ubiquitination of HIF, causing proteasomal degradation
  1. hypoxia
    - PHD2 can not function anymore, does not sense oxygen, so because of that, HIF ubiquitination can not take place so it can not be degraded : call the process stabilization of HIF
    - Once the HIFa is stabilize, it requires HIFb to be a functional dimer,
    - Once they dimerize, they can enter in the nucleus, so since they are transcription factors, they have to identified there HREs (hormone response elements which is a specific sequence of DNA)
17
Q

target genes during hypoxia (not enough oxygen)

A
GLUT 1/3
hexokinase
PFK
aldolase
GAP
phosphoglycerate kinase
phosphoglycerate mutase
enolase
lactate dehydrogenase (Lactate dehydrogenase that converts the pyruvate into lactate so make the glycolysis continues by creating NAD+)
18
Q

gluconeogenesis: site, substrates

A
  • pyruvate and related 3-4C compunds (like lactose, AA, glycerol) are converted to glucose
  • site: mainly liver, also renal cortex and intestinal epithelium
  • gluconeogenesis after doing exercise for recovery (the lactate generates in the muscles by anaerobic glycolysis will go to the liver where it will be convert back into glucose which move back to muscle where it is converted into glycogen)
  • tissues like brain, RBC,embryo, renal medulla, testes depend mainly on glucose
    • Plants are the only ones that can converts CO2 to carbon through the Calvin cycle
    • animals do not use FA for gluconeogenesis
19
Q

number of enzymes implied in gluconeogenesis + synthesize of one glucose requires what

A
  • it requires 6 ATP and 2 NADH
    ** the step for the conversion of pyruvate to PEP require 2 enzymes (not only one like in glycolysis which is the pyruvate kinase):
    1. pyruvate carboxylase to convert pyruvate to oxaloacetate in mitochondria
    2. PEP carboxylase to convert oxaloacetate to PEP in mitochondria/cytosol
    so gluconeogenesis require 11 enzymes whereas glycolysis require 10 i
  1. fructose 1,6, biphosphataste to convert fructose 1,6, biphosphate to fructose 6 phosphate
  2. glucose 6 phosphate to glucose by glucose 6-phosphatase
20
Q

which amino acids (2) are unable to furnish carbon for net glucose synthesis

A
  • lysine and leucine (they are also ketogenic)
    • the other ones are all precursors of blood glucose or liver glycogen, because they can be converted to pyruvate or citric acid cycle intermediates
21
Q

4 steps of the urea cycle

A
  1. enzyme: ornithine trans-carbamoylase. Form citruline (in the mitochondria) from ornithine and carbamoyl phosphate (entry of the first amino group). The citruline passed into the cytosol
    1. enzyme: argininosuccinate synthetase. Citruline goes out the mitochondria where other enzymes use energy and create an intermediate which will interact with the aspartate (entry of the second amino group) to create arginosuccinate
    2. enzyme: argininosuccinase. Form arginine from arginiosuccinate; this reaction releases furamate and it can go to the TCA cycle
    3. enzyme: arginase. Formation of urea; this reaction also regenerates ortnithine
22
Q

regulation of urea cycle: 4 situations where it increases + how it is regulated

A
    • when acetyl-coa and glutamate are high: it will form N-acetylglutamate by the enzyme N-acetylglutamate synthase and this will activate the enzyme carbamoyl phosphate synthetase 1
  • expression of urea cycle enzymes increase during:
    1. high protein diet
    2. starvation
    3. uncontrolled diabetes
    4. tumor
23
Q

link between urea cycle and TCA cycle

A
  • Urea cycle can not continue without TCA cycle because it requires aspartate which come from oxaloacetate which is a TCA cycle intermediate (has to be taken out to create asparate to start urea cycle)
    • 2 important enzymes (both cytolisic and mitochondrial isoforms):
      1. Malate dehydrogenase converts malate to oxaloacetate
      2. Fumarase converts fumarate to malate
      ** these enzymes are present in both mitochondria and cytoplasm!!
      ** so urea depends on the TCA cycle because of oxaloacetate
  • Only malate can be transport into the mito because has malate transporter but ultimately it will come back as fumarate to continue the TCA cycle
    (fumarate does not have transporter to directly move it from cytosol to mitochondria so has to converted it to malate)
24
Q

5 AA that are both ketogenic and glucogenic
+ particularity with leucine and lysine
+ role of leucine, isoleucine and valine

A
tryptophan
phenylalanine
tyrosine
threonine
isoleucine
** LYSINE AND LEUCINE: 2 AA that are only present in acetyl-coa!! These 2 amino acids can only be ketogenic *there are inno other columns)
  • Leucine, isoleucine and valine are used as fuel in muscle/adipose/brain-
    Branched-chain aminotransferase is only expressed in extra-hepatic tissues
25
Q

AA where end product are : pyruvate (6), acetyl-coa (7), a-ketogultarate (5), succinyl-coa (4), oxaloacetate (2), fumarate (2)

A
  • Pyruvate:
    1. Alanine
    2. Tryptophan
    3. Cysteine
    4. Serine
    5. Glycine
    6. Threonine
    • Acetyl-coa:
      1. Tryptophan
      2. LYSINE
      3. LEUCINE
      4. Phenylalanine
      5. Tyrosine
      6. Isoleucine
      7. Threonine
    • A-ketoglutarate
      1. Proline
      2. Glutamate
      3. Glutamine
      4. Arginine
      5. Histidine
    • Succiniyl-coaL
      1. Methionine
      2. Isoleucine
      3. Threonine
      4. Valine
    • Oxaloacetate
      1. Asparagine
      2. Aspartate
    • Fumarate
      1. Phenylalanine
      tyrosine
26
Q

regulation of AA metabolism

A
  1. First step of AA catabolism is transfer of the NH3 usually to a-ketoglutarate to yield L-glutamate
    1. Ammonia is quickly recaptured into carbamoyl phosphate and passed into the urea cycle
    2. AA are degraded to pyruvate, acetyl-coa, a=ketoglutarate, succinyl-coa, and/or oxaloacetate (intermediate of the TCA cycle)
    3. Glutamate dehydrogenase is regulated: ADP (+) and GTP (-)
    4. All 4 enzymes of urea cycle and carbamoyl phosphate synthase I are regulated by nutritional status (diet and starvation)
      High energy (ATP) used by urea cycle is offset by NADH (2.5 ATP) malate-oxaloacetate conversion reaction
27
Q

pentose phosphate pathway, common in which type of cells

A
  • Glycolysis is the most common fate of G6P
    • Alternative fat: pentose phosphate pathway (hexose monophosphate pathway)
      More common in:
      1. Highly proliferative cells (like cancer cells)
      2. Cells of FA biosynthesis
      3. Cells of sterols (cholesterol and steroids) synthesis
      Cells with oxidative stress
28
Q

pentose phosphate pathway: oxidative phase

A
  1. Glucose-6-phosphate go through multiple enzymatic reactions which involve a lot of enzymes but the one to remember are :
    G6P dehydrogenase (don’tc confuse with GAPDH) which begin the process and phospho-pentose isomerase which is important to create ribose-5-phosphate
    ** these reactions generate NADPH which is very important electron donor for certain enzymes to be functional (like enzymes of FA synthesis in liver,kidney and lactating mammary or cholesterol/steroid synthesis in liver, adrenal and gonads) they do reductive biosynthesis which need a source of H (so this source is NADPH)
    ** NADPH prevents oxidative damages to proteins, lipids and other sensitive molecules
    Also, glutathione reductase is important for oxidative stress
29
Q

what happened if tissues required more NADPH than ribose-5-phosphate

A

ribose 5 phosphate will be converted to glucose-6-phosphate by some intermediates (transkelotase and transaldolase)

30
Q

regulation of pentose phosphate pathway

A

When NADPH is forming faster than it is bein used for biosynthesis and glutathione reduction, concentration of NADPH rises and inhibits the first enzyme of the pentose phosphate pathway (glucose 6-phosphate dehydrogenase) More glucose-6-phosphate is then available for glycolysis