Lectures 9-10 - Glucose metabolism Flashcards

1
Q

How are carbs digested in humans? 4 steps (hint: where, what into what? by what?)

A
  1. Mouth: dietary carbs to polysacs, sucrose, lactose, maltose by salivary amylases
  2. Stomach: no digestion of carbs because low pH inactivates low pH
  3. Pancreas: polysacs, sucrose, lactose, maltose into monosacs (glucose, galactose, fructose) by pancreatic amylase
  4. Small intestin: absorption of monosacs into bloodstream through active transport
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2
Q

why is glucose an excellent fuel? (3)

A
  • yields good amount of energy
  • can be efficiently stored
  • many tissues can meet energy needs on glucose only
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3
Q

glucose is a precursor to 4 things?

A
  1. all the amino acids
  2. membrane lipids/Fatty acids
  3. nucleotides in DNA and RNA
  4. cofactors in metabolism
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4
Q

Glucose can have 4 purposes/fates

A
  1. storage by converting to glycogen, starch, sucrose
  2. oxidation via glycolysis by converting to pyruvate –> energy
  3. oxidation via pentose phosphate pathway by converting to ribose 5-phosphate –> nucleic acid synthesis
  4. synthesis of structural polymers by converting to extracellular matrix and cell wall polysaccharides
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5
Q

What is glycolysis? in terms of glucose transformation

A

glucose is degraded to 2 pyruvates

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6
Q

What is gluconeogenesis? in terms of glucose transformation

A

glucose is formed from non-carbohydrate sources

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7
Q

What is glycogenesis? in terms of glycogen transformation

A

glycogen polymerized from glucose units

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8
Q

What is glycogenolysis? in terms of glycogen transformation

A

glycogen is degraded to glucose units

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9
Q

what is fermentation?

A

anaerobic degradation of glucose to obtain energy conserved as ATP

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10
Q

kinases are enzymes that?

A

transfer phosphate groups btw ATP and various substrates

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11
Q

mutases catalyze what?

A

migration of functional groups

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12
Q

which mammalian tissues/cell types has glycolysis as sole source of metabolic energy? (4)

A
  • erythrocytes
  • brain
  • sperm
  • renal medulla
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13
Q

free energy released in glycolysis is conserved as (2)

A

ATP and NADH

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14
Q

glycolysis is evolutionarily conserved. what does it mean?

A

almost same in all species
- differs among species in details of regulation of glycolysis and fate of pyruvate formed

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15
Q

how many ATP consumed/produced in prep phase/payoff phase of glycolysis? net?

A
  • prep phase: use 2 ATPs
  • pay-off: produce 4 ATPs
  • Net: gain 2 ATP
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16
Q

Step 1 of glycolysis
- what to what?
- type of reaction?
- enzyme? types?
- goal (2)
- reversible?
- uses ATP?

A
  • glucose –> glucose 6-phosphate
  • phosphorylation
  • hexokinase –> 4 isoforms
  • traps glucose inside cell –> lowers intracellular unphosphorylated glucose to allow further uptake
  • irreversible
  • yes! and Mg2+
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17
Q

Step 2 of glycolysis
- what to what?
- type of reaction?
- enzyme?
- goal (2)
- reversible?
- uses ATP?

A
  • glucose 6 phosphate to fructose 6 phosphate
  • isomerization
  • phosphohexose isomerase
  • Makes next steps easier: C1 of fructose easier to phosphorylate by PFK + allows for symmetrical cleavage by aldolase
  • reversible
  • no!
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18
Q

Step 3 of glycolysis
- what to what?
- what type of reaction?
- enzyme?
- goal
- reversible?
- uses ATP?

A
  • fructose 6-phosphate to fructose 1,6-bisphosphate
  • 2nd priming phosphorylation
  • phosphofructokinase-1 (PFK-1)
  • generates a symmetric 6 carbon molecule
  • irreversible
  • yes!
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19
Q

What is the first committed step of glycolysis

A

step 3: 2nd priming phosphorylation –> formation of fructose 1,6-bisphosphate

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20
Q

Step 4 of glycolysis
- what to what?
- what type of reaction?
- enzyme?
- goal
- reversible?
- uses ATP?

A
  • fructose 1,6-bisphosphate to dihydroxyacetone phosphate (DHAP) AND glyceraldehyde 3-phosphate (GAP)
  • aldol cleavage/lysis
  • aldolase
  • 6C sugar cleaved into two 3-C high energy phosphate sugars
  • reversible
  • no!
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21
Q

Step 5 of glycolysis
- what to what?
- what type of reaction?
- enzyme?
- goal
- reversible?
- uses ATP?

A
  • dihydroxyacetone phosphate to glyceraldehyde 3-phosphate
  • triose phosphate interconversion
  • triose phosphate isomerase
  • conver DHAP to GAP because only GAP is substrate for next enzyme
  • reversible
  • no
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22
Q

Step 6 of glycolysis
- what to what?
- what type of reaction?
- enzyme?
- goal
- reversible?
- uses smtg?

A
  • GAP and Pi to 1,3-bisphosphoglycerate
  • oxidation of GAP
  • glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
  • produces first energy-rich molecule –> oxidation of GAP with NAD+ gives NADH
  • reversible
  • inorganic phosphate and NAD+
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23
Q

Step 7 of glycolysis
- what to what?
- what type of reaction?
- enzyme?
- process
- reversible?
- uses smtg?

A
  • 1,3-bisphosphoglycerate + ADP –> 3 phosphoglycerate + ATP
  • substrate level phosphorylation (no oxidation required)
  • phosphoglycerate kinase
  • 1,3-bisphosphoglycerate donates phosphate group to ADP to make ATP
  • reversible
  • uses ADP and Mg2+
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24
Q

Step 8 of glycolysis
- what to what?
- what type of reaction?
- enzyme?
- process?
- reversible?
- uses smtg?

A
  • 3-phosphoglycerate to 2-phosphoglycerate
  • migration of phosphate
  • phosphoglycerate mutase
  • phosphohistidine of enzyme donates its phosphate to 3-phosphoglycerate at the 2 carbon before retreiving phosphate from 3-carbon
  • reversible
  • Mg2+
25
Q

Step 9 of glycolysis
- what to what?
- what type of reaction?
- enzyme?
- goal
- reversible?
- uses/produces smtg?

A
  • 2-phosphoglycerate to phosphoenolpyruvate
  • dehydration
  • enolase
  • generates high energy phosphate compound
  • reversible
  • produces H2O
26
Q

Step 10 of glycolysis
- what to what?
- what type of reaction?
- enzyme?
- goal
- reversible?
- uses smtg?

A
  • phosphoenolpyruvate –> pyruvate + ATP
  • substrate level phosphorylation
  • pyruvate kinase
  • 2nd production of ATP
  • irreversible
  • requires metal ions for activity! (Mg2+, K+)
27
Q

Summary of glycolysis:
- 5 different things used?
- 6 different things produced?

A
  • 1 glucose, 2 NAD+, 2 ATP, 2 Pi, 4 ADP
  • 2 pyruvate, 2 NADH, 4 ATP, 2 ADP, 2 H+, 2 H2O
28
Q

why is glycolysis heavily regulated (2)?

A
  • ensure proper use of nutrients
  • ensure production of ATP when needed
29
Q

3 fates of pyruvate (there are 2 pyruvates from 1 glucose)
- what condition? + transformation + in what type of cells

A
  1. Aerobic conditions: oxidated to acetyl-coa –> oxidized again in citric acid cycle to form 4 CO2 + 4 H2O –> in animal, plant and many microbial cells
  2. hypoxic or anaerobic conditions: catabolized to 2 ethanol and 2 CO2 –> fermentation to ethanol in yeast
  3. hypoxic or anaerobic conditions: catabolized to 2 lactate –> fermentation to lactate in vigorously contracting muscle, in erythrocytes, in some other cells and in some microorganisms
30
Q

if oxygen is not available (_______ or ________ condition):
- ___A__ is required for glycolysis to continue
- ___A___ is generated by converting ________ to ____B____ –> ________ can do that!
- B is converted to glucose in _________ (where) –> in the _____ cycle

A
  • hypoxic or anaerobic condition
  • NAD+
  • converting pyruvate to lactate
  • erythrocytes can do that
  • Lactate converted back to glucose in liver in the Cori cycle
31
Q

which enzyme converts pyruvate to lactate? using which cofactor? and producing what?

A

lactate dehydrogenase
- using NADH and H+
- producing NAD+

32
Q

which tissues depend mainly on glucose? (5)

A
  • brain
  • RBC
  • testes
  • renal medulla
  • embryo
33
Q

recovery after vigorous exercise involves ?

A

gluconeogenesis

34
Q

gluconeogenesis = ________ and related _- or _-carbon compounds (3 examples?) are converted to ___________

A
  • pyruvate and related 3 or 4 carbon compounds
  • ie lactate, glycerol, glucogenic, amino acid
  • converted to glucose
35
Q

main site + 2 other of gluconeogenesis

A
  • mainly liver
  • renal cortex and intestinal epithelium
36
Q

can animals use fatty acids for gluconeogenesis?

A

No

37
Q

who can use CO2 fo make glucose? (2)

A

plants and photosynthetic bacteria

38
Q

pyruvate enters what to make glucose?

A

citric acid cycle through oxaloacetate

39
Q

steps for glycolysis
and gluconeogenesis: differences and similarities

A
  • 7 steps are exactly the same/reversible –> same enzymes!
  • 3 steps of glycolysis are irreversible (step 1 (G to G-6P), step 3 (F 6P to F 1,6 bP) and step 10 (phosphoenol pyruvate to pyruvate))
  • for gluconeogenesis: step 1 replaced by glucose 6-phosphatase, step 3 replaced by fructose 1,6-bisphosphatase, step 10 replaced by pyruvate carboxylaze and PEP carboxykinase
40
Q

synthesis of 1 glucose molecule requires __ ATPs (__ ATP + __ GTP) and ___ NADHs

A
  • 6 ATPs (4 ATP and 2 GTP)
  • 2 NADH
41
Q

5 steps of synthesis of phosphoenol pyruvate from pyruvate

A
  1. Pyruvate transported from cytosol to mitochondria OR alanine already in mitochondria (?)
  2. pyruvate + bicarbonate –> oxaloacetate. enzyme: pyruvate carboxylase using ATP and biotin as coenzyme
  3. oxaloacetate needs to be reduced to malate bc mitochondria doesn’t have membrane transporter for oxaloacetate
  4. in cytosol, malate reoxidized to oxaloactate
  5. oxaloacetate + GTP –> phosphoenol pyruvate. enzyme: PEP carboxykinase, releasing GDP and CO2
42
Q

can all amino acids furnish carbon for net glucose synthesis?

A

no! all 20 aa can, except for leucine and lysine

43
Q

amino acids are precursors of glucose are ____________?

A

glucogenic (and some are also ketogenic)

44
Q

what is an alternate fate to glycolysis of glucose 6 phosphate?

A

pentose phosphate pathway (or hexose monophosphate pathway)

45
Q

pentose phosphate pathway is more common in (4)

A
  • highly proliferative cells (ie skin)
  • in cells of FA biosynthesis
  • in cells of sterols synthesis (cholesterol and steroids)
  • in cells with oxidative stress/tissues exposed to high O2 (cornea and RBC)
46
Q

is ATP consumed or produced in pentose phosphate pathway?

A

nope!

47
Q

oxidative phase of pentose phosphate pathway. 3 steps

A
  1. glucose 6-phosphate –> 6-phosphogluconate through G6P dehydrogenase + NADP+ (oxidized) –> NADPH
  2. 6-phosphogluconate –> ribulose 5-phosphate, NADP+ –> NADPH
  3. ribulose 5-phosphate –> ribose 5 phosphate through phospho pentose isomerase
48
Q

ribose 5-phosphate important to synthesize (4) –> for (2)

A
  • nucleotides, coenzymes, DNA, RNA
  • for proliferation and gene expression
49
Q

what needs the NADPH produced in pentose phosphate pathway to maintain reductive atmosphere? (3)

A
  • FA synthesis in liver
  • adipose tissues
  • lactating mammary glands
50
Q

what counters the effect of oxidative radical stress/damage?/needs reductive atmosphere? (3)

A
  • cholesterol/steroid synthesis in liver
  • adrenal
  • gonads
51
Q

net result of pentose phosphate pathway? (2 + use of each)

A
  • production of NADPH: reductant for biosynthetic reactions
  • production of ribose-5-phosphate –> precursor for nucleotide synthesis
52
Q

how does pentose phosphate pathway prevent oxidative damage? 3 steps
(review schéma!)

A
  1. glucose6P to 6-phosphoglucono-lactone through glucose 6P dehydrogenase–> converts NADP+ to NADPH
  2. NADPH reduces GSSG to 2GSH through glutathione reductase
  3. GSH blocks oxidative damage of hydroxyl free radical to lipids, proteins, DNA –> converts HOOH to H2O through glutathione peroxidase (converts GSH back to GSSG)
53
Q

GSH and GSSG –> which is reduced/oxidized?

A
  • GSH: reduced form of glutathione
  • GSSG: oxidized form of glutathione
54
Q

what deficiency can be fatal in cases of high oxidative stress?
- this deficiency can lead to ? what are most susceptible?

A

deficiency in G6P dehydrogenase
- lead to hemolytic anemia –> leads to peroxidation
- RBCs are most susceptible

55
Q

what does non-oxidative phase of pentose phosphate pathway do?
- used in tissues with what characteristic?

A

regenerates G-6-P from ribose 5-phosphate
- tissues requiring more NADPH than R-5-P

56
Q

6 steps of non oxidative phase of pentose phosphate pathway?

A
  1. ribose 5P to xyllulose 5-phosphate (5C) through isomerase and epimerase
  2. xylulose 5 phosphate to glyceraldehyde 3P (3C) through transketolase (ALSO ribose 5-P to sedoheptulose 7 phosphate (7C))
  3. glyceraldehyde 3P to erythrose 4 phosphate (4C) through transaldolase (ALSO sedoheptulose 7P to fructose 6P (6C)
  4. erythrose 4-P to fructose 6P (6C) through transketolase (ALSO xylulose 5P to glyceraldehyde 3P)
  5. glyceraldehyde 3P can be converted to fructose 6P through triose phosphate isomerase + aldolase + fructose 1,6 bisphosphatase
    (glyceraldehyde 3P can also be oxidized to pyruvate depending on what the cell needs)
  6. Fructose 6P to glucose 6P through phosphohexose isomerase
57
Q

are reactions of the non-oxidative phase of pentose phosphate pathway reversible?

A

yes!

58
Q

how is pentose phosphate pathway regulated?

A

excess NADPH will inhibit first enzyme in pentose phosphate pathway
- result: more glucose 6P is available for glycolysis

59
Q

G6P partitioning depends on (2)

A
  • depends on cell’s needs
  • NADP+ activates G6P dehydrogenase (= more pentose phosphate pathway)