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FHB Exam 3 > Metabolism: Glycolysis > Flashcards

Metabolism: Glycolysis Flashcards

1
Q

What are the reduced and oxidized forms of NAD/NADH? What is the function of each?

A 
reduced = NADH (reducing agent donates H+ to substrate)
oxidized = NAD+ (oxidizing agent pulls H+ off substrate)
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2
Q

What are the reduced and oxidized forms of NAD/NADH? What is the function of each?

A 
reduced = NADH (reducing agent donates H+ to substrate)
oxidized = NAD+ (oxidizing agent pulls H+ off substrate)
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3
Q

What is the fuel preference for liver?

A

FA
glucose
AA

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4
Q

What is the fuel preference for adipose?

A

FA

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5
Q

What is the fuel preference for the heart?

A

FA

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6
Q

What is the fuel preference for the skeletal muscle?

A

at rest = FA

during activity = glucose

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7
Q

What is the fuel preference for the brain?

A 
NEEDS glucose => quickly dies
if none (starvation) = ketone bodies
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8
Q

List the number of calories you get from each macromolecule.

A 
CHO = 4 kcal/g
protein = 4 kcal/g
fat = 9 kcal/g
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9
Q

Define hypoglycemia and its effects.

A
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10
Q

Define hyperglycemia and its effects.

A

> 110mg/100mL

  • insulin intolerance/beta cell dysfunction, glucose intolerance, T2M
  • oxidative stress
  • lipotoxicity
  • osmotic burden
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11
Q

Define glycogenolysis.

A
  • breakdown of glycogen to increase blood glucose levels

- induced by glucagon and epinephrine

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12
Q

Define glycogenesis.

A
  • anabolism of glucose to create glycogen to store glucose

- induced by insulin

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13
Q

Define glycolysis.

A
  • breakdown of glucose to generate pyruvate/lactate and energy, and substrates for TCA cycle
  • induced by insulin and high BG
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14
Q

Define gluconeogenesis.

A
  • only in the liver
  • reversing glycolysis to generate glucose from pyruvate
  • induced by glucagon and epinephrine
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15
Q

What are the 3 stages of glycolysis? What is the main end-product of each?

A
  1. priming = F16BP
  2. splitting = GAP/DHAP
  3. oxidoreduction-phosphorylation stage = pyruvate
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16
Q

List the 3 main glycolytic enzymes.

A
  1. hexo-/glucokinase
  2. PFK1
  3. pyruvate kinase
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17
Q

List the main steps in glycolysis.

A
  1. glucose => G6P (hexo/glucokinase)
  2. G6P => F6P (isomerase)
  3. F6P => F16BP (PFK1)
  4. F16BP => DHAP/GAP (aldolase A)
  5. DHAP => GAP (isomerase)
  6. GAP => 13BPG (GAP dehydrogenase)
  7. 13BPG => 3-phosphoglycerate (phosphoglycerate kinase)
  8. 3-PG => 2-PG (mutase)
  9. 2-PG => PEP (enolase)
  10. PEP => Pyruvate (pyruvate kinase)
  11. Pyruvate => lactate (LDH)
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18
Q

List the main steps in glycolysis.

A
  1. glucose => G6P (hexo/glucokinase)
  2. G6P => F6P (isomerase)
  3. F6P => F16BP (PFK1)
  4. F16BP => DHAP/GAP (aldolase A)
  5. DHAP => GAP (isomerase)
  6. GAP => 13BPG (GAP dehydrogenase)
  7. 13BPG => 3-phosphoglycerate (phosphoglycerate kinase)
  8. 3-PG => 2-PG (mutase)
  9. 2-PG => PEP (enolase)
  10. PEP => Pyruvate (pyruvate kinase)
  11. Pyruvate => lactate (LDH)
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19
Q

What is the fuel preference for liver?

A

FA
glucose
AA

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20
Q

What is the fuel preference for adipose?

A

FA

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21
Q

What is the fuel preference for the heart?

A

FA

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22
Q

What is the fuel preference for the skeletal muscle?

A

at rest = FA

during activity = glucose

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23
Q

What is the fuel preference for the brain?

A 
NEEDS glucose => quickly dies
if none (starvation) = ketone bodies
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24
Q

List the number of calories you get from each macromolecule.

A 
CHO = 4 kcal/g
protein = 4 kcal/g
fat = 9 kcal/g
25
Describe the regulation of pyruvate kinase.
via phosphorylation - F16BP, high BG, insulin promote dephosphorylation to active form (phosphoprotein phosphatase) - ATP, alanine, low BG, glucagon, epi promote phosphorylation to inactive form (PKA)
26
Define hyperglycemia and its effects.
>110mg/100mL - insulin intolerance/beta cell dysfunction, glucose intolerance, T2M - oxidative stress - lipotoxicity - osmotic burden
27
Define glycogenolysis.
- breakdown of glycogen to increase blood glucose levels | - induced by glucagon and epinephrine
28
Describe the effects of Pyruvate Carboxylase deficiency.
- genetic - increased accumulation of alanine, lactate, pyruvate - developmental delay, seizures, acidosis
29
Define glycolysis.
- breakdown of glucose to generate pyruvate/lactate and energy, and substrates for TCA cycle - induced by insulin and high BG
30
Define gluconeogenesis.
- only in the liver - reversing glycolysis to generate glucose from pyruvate - induced by glucagon and epinephrine
31
What are the 3 stages of glycolysis? What is the main end-product of each?
1. priming = F16BP 2. splitting = GAP/DHAP 3. oxidoreduction-phosphorylation stage = pyruvate
32
List the 3 main glycolytic enzymes.
1. hexo-/glucokinase 2. PFK1 3. pyruvate kinase
33
What are the 4 enzymes utilized for gluconeogenesis?
1. pyruvate => oxaloacetate via pyruvate carboxylase 2. oxaloacetate => PEP via PEP carboxykinase 3. F16BP phosphatase 4. G6P phosphatase
34
List the main steps in glycolysis.
1. glucose => G6P (hexo/glucokinase) 2. G6P => F6P (isomerase) 3. F6P => F16BP (PFK1) 4. F16BP => DHAP/GAP (aldolase A) 5. DHAP => GAP (isomerase) 6. GAP => 13BPG (GAP dehydrogenase) 7. 13BPG => 3-phosphoglycerate (phosphoglycerate kinase) 8. 3-PG => 2-PG (mutase) 9. 2-PG => PEP (enolase) 10. PEP => Pyruvate (pyruvate kinase) 11. Pyruvate => lactate (LDH)
35
Describe the reaction carried out by hexokinase.
- occurs in all cells - irreversible (require G6P phosphatase to reverse) - locks glucose in G6P (can't leave cell) - low Km, high affinity (easily maximized at normal physiological levels) - constant amount - insulin independent - allosteric negative feedback inhibition by G6P
36
Describe the reaction carried out by glucokinase.
- only occurs in the liver and pancreas - insulin dependent - high Km, low affinity (phosphorylates in proportion to the amount in the blood) - in the nucleus (inactive); in the cytosol (active) - F6P promotes translocation to nucleus (no longer needed; have enough) - glucose promotes translocation to the cytosol (needed for glycolysis)
37
Describe the function of PFK2.
- converts F6P to F16BP - bifunctional (kinase and phosphatase, but never both at the same time) - irreversible
38
What factors affect F16BP levels?
- activators = insulin, high BG | - inhibitors = glucagon, epinephrine, low BG
39
Describe the relationship between F16BP and PFK1.
F16BP activates PFK1 to promote glycolysis
40
Describe the mechanism of glucagon/epinephrine inhibition of PFK2 in the liver.
1. glucagon/epi => cAMP => PKA => phosphorylation of kinase domain of PFK2 2. kinase activity is inhibited, phosphatase activity is activated 3. F16BP is converted to F6P 4. PFK1 is inhibited 5. glycolysis is inhibited
41
Describe the mechanism of glucagon/epinephrine effect on PFK2 in the heart and skeletal muscle.
NOTE: only the liver is affected by glucagon 1. epi => cAMP => PKA => phosphorylation of phosphatase domain of PFK2 2. phosphatase activity is inhibited, kinase activity is activated 3. F6P is converted to F16BP 4. PFK1 is activated 5. glycolysis is activated
42
Describe the regulation of pyruvate kinase.
via phosphorylation - F16BP, high BG, insulin promote dephosphorylation to active form (phosphoprotein phosphatase) - ATP, alanine, low BG, glucagon, epi promote phosphorylation to inactive form (PKA)
43
List the 4 fates of pyruvate.
1. pyruvate => acetyl-CoA => TCA (via PDH) 2. pyruvate => lactate (via LDH) 3. pyruvate => oxaloacetate (via pyruvate carboxylase) 4. pyruvate => alanine (via transaminase)
44
Describe the effects of PDH deficiency.
- genetic - increased pyruvate and lactate accumulation - microcephaly, mental retardation, poor muscle coordination
45
Describe the effects of Pyruvate Carboxylase deficiency.
- genetic - increased accumulation of alanine, lactate, pyruvate - developmental delay, seizures, acidosis
46
Why is the NAD+/NADH ratio so important? How is it maintained?
- NAD+ is present in little amount in the cytoplasm. It needs to be regenerated in order for glycolysis to continue. - anaerobic: reduction of pyruvate to lactate or ethanol regenerates NAD+ (LDH) - aerobic: mitochondrial metabolite shuttle system (malate asparatate or glycerol phosphate), ETC
47
What processes require oxygen (aerobic)?
- pyruvate dehydrogenase activity (reoxidation of NADH) | - metabolic shuttle in mitochondria
48
Describe the lactate dehydrogenase reaction.
pyruvate + NADH lactate + NAD+ - if you have low levels of NADH, you will not be able to generate lactate - this is anaerobic - in muscles, prefer production of lactate - in heart, prefer production of pyruvate
49
Describe the components of PDH.
E1, E2, E3 | converts Pyruvate to acetyl-CoA
50
Which vitamins are required for proper PDH activity?
``` E1 = thiamin (B1 - in form of thiamine pyrophosphate) E2 = lipoate CoA (B5 - pantothenate) E3 = FAD/NAD (B2 - riboflavin, B3 - niacin) ```
51
How is PDH regulated?
allosteric negative feedback inhibition - acetyl-CoA - NADH
52
Describe the effects of a LDH deficiency.
- genetic recessive - poor muscle control because can't undergo glycolysis to make ATP - can't regenerate enough NAD+
53
What is the net ATP production of glycolysis?
2 ATP 2 NADH 2 H+ 2 H2O
54
How does galactose contribute to glycolysis?
galactose => galactose-1P (via galactokinase) | galactose-1P => glucose-1P (via gal-1P uridyltransferase)
55
Which enzyme deficiencies cause galactosemia?
- galactokinase | - gal-1P uridyltransferase (most common)
56
What is the effect of galactosemia and the treatment?
genetic deficiency of enzymes - cataracts due to galactose accumulation => galactitol - galactosuria - if classic: hepatic dysfunction, brain dysfunction tx: remove galactose from diet (remove lactose, milk)
57
What is the function of aldolase B?
inserts fructose into the glycolysis cycle
58
Describe hereditary fructose intolerance.
- autosomal recessive deficiency of aldolase B - accumulation of fructose - hypoglycemia, vomiting, jaundice, hepatic failure tx: avoid fructose

FHB Exam 3 (23 decks)

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