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Biochemistry Exam 2 > Glycolysis > Flashcards

Glycolysis Flashcards

1
Q

What is the glycolytic pathway?

A

Employed by all tissues for oxidation of glucose to provide energy (ATP) and intermediates for other metabolic pathways

  • the hub of carbohydrate metabolism (all sugars can be converted to glucose)
  • RBCs only do glycolysis (never enter TCA) so would die without it
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2
Q

What is the end product of glycolysis?

A

Pyruvate

  • in aerobic environments -> pyruvate enters TCA cycle for oxphos/ETC
  • in anaerobic environments -> pyruvate reduced to lactate
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3
Q

What is Na-independent facilitated diffusion?

A

Transport of glucose by a family of membrane transporters (GLUT-1 to GLUT-14)

  • tissue-specific expression
  • GLUT-4 abundant in muscle and adipose, increased by insulin
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4
Q

What is Na+ co-transport?

A 
Energy requiring (against the monosaccharide gradient), Na-dependent transport of glucose
-found in intestine and renal tubules
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5
Q

What are the 2 stages of glycolysis?

A

1) Energy investment prep phase: 1st 5 rxns

2) Energy generation phase: net 2 ATPs (total 4)

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6
Q

What is the E-investment prep phase (step 1) of glycolysis?

A

Glucose -> Glucose 6-phosphate

  • Enzyme: Hexokinase I-III or Glucokinase
  • Irreversible reaction #1 (phosphorylation prevents sugar from being able to leave the cytosol)
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7
Q

What is the Km/Vmax of Hexokinase I-III?

A
  • Low Km (high affinity): important to RBCs because they need high affinity for glucose since they only perform glycolysis
  • Low Vmax
  • Inhibited by product
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8
Q

What is the Km/Vmax of Glucokinase (Hexokinase IV)?

A
  • Much higher Km (lower affinity): present in the liver parenchymal cells and beta-cells of pancreas (only needs to be effective at high levels of glucose for glycogen production)
  • High Vmax
  • Not inhibited by product
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9
Q

What is step 2 of glycolysis?

A

Isomerization of Glucose 6-P -> Fructose 6-P

  • Enzyme: phosphoglucose isomerase
  • Reversible
  • Not a rate-limiting or regulated step
  • Most likely not on test
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10
Q

What is step 3 of glycolysis?

A

Fructose 6-P -> Fructose 1,6-biphosphate

  • Enzyme: phosphofructokinase 1
  • Irreversible, most rate-limiting and committed step (aka point of no return)
  • Inhibited by: increase in ATP and increase in Citrate
  • Activated by: Fructose 2,6-biphosphate and AMP
  • Phosphorylation adds an additional phosphate (uses energy)
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11
Q

What is step 4 of glycolysis?

A

Fructose 1,6-biphosphate -> glyceraldehyde 3 phophate + dihydroxyacetone phosphate

  • Enzyme: Aldolase
  • Reversible, not rate-limiting or regulated
  • Aldolase B also cleaves fructose 1-P (dietary fructose)
  • DHAP -> G3P via Triose phosphate isomerase (so you end up with 2 G3P)
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12
Q

What is step 5 of glycolysis?

A

Glyceraldehyde 3-P -> 1,3-biphosphoglycerate (1,3-BPG)

  • Enzyme: Glyceraldehyde 3-phosphate dehydrogenase
  • 1st redox (oxidation-reduction) rxn
  • Requires 1 ATP and produces NADH (2 G3P -> 2 NADH)
  • High-energy phosphate at C1 drives following ATP synthesis
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13
Q

What is step 1 of the E-generation phase of glycolysis?

A

Each step occurs twice because we started with 2 G3P
1,3-biphosphoglycerate -> 3-phosphoglycerate
-Enzyme: Phosphoglycerate kinase
-Makes 1st ATP via substrate level phosphorylation (does not require oxygen, energy for production of high-energy P comes from substrate)
-3-phosphoglycerate -> 2-phosphoglycerate

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14
Q

What side step can RBCs take during step 1 of the E-generation phase?

A

1,3-BPG -> 2,3-BPG

  • Enzyme: Mutase
  • Does not make ATP
  • Bypass done to regulate O2 affinity
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15
Q

What is step 2 of the E-generation phase of glycolysis?

A

2-phosphoglycerate -> phosphoenolpyruvate

  • Enzyme: Enolase
  • Dehydration reaction causes phosphoenolpyruvate to become high-energy
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16
Q

What is step 3 of the E-generation phase of glycolysis?

A

Phosphoenolpyruvate -> pyruvate

  • Enzyme: Pyruvate kinase
  • Irreversible
  • ATP is created via substrate level phosphorylation
  • Activated by fructose 1,6-biphosphate
17
Q

What does fluoride inhibit?

A

Enolase

-Water fluoridation reduces lactate production by mouth bacteria, decreasing dental cavities

18
Q

How is pyruvate reduced to lactate?

A

By lactate dehydrogenase

  • Reversible enzyme
  • Major fate in lens/cornea of eye, kidney, medulla, testes, leukocytes and RBCs because they are all poorly vascularized (low O2) or lack mitochondria (no TCA)
  • Important in low O2 situations because it allows the oxidation of NADH -> NAD+ (a build-up of NADH is rate limiting in many reactions so this would inhibit glycolysis)
19
Q

What occurs in exercising skeletal muscle?

A
  • When NADH production exceeds the oxidative capacity of the respiratory chain -> elevated NADH/NAD+ ratio -> favors reduction of pyruvate to lactate
  • During intense exercise: lactate accumulates in muscle -> drop in intracellular pH -> cramps
20
Q

What does LDH activity depend on?

A

Intracellular concentration of pyruvate, lactate and on NADH/NAD+ ratio
-In liver and heart, NADH/NAD+ ratio is lower than in exercising muscle -> oxidize lactate (obtained from the blood) back to pyruvate

21
Q

What is lactic acidosis?

A

Elevated [lactate] in plasma (a type of metabolic acidosis) when there is a collapse of circulatory system (such as in MI, PE, and uncontrolled hemorrhage)

  • O2 is not brought to tissues effectively -> limits oxphos and decreases ATP synthesis
  • Cells rely on anaerobic glycolysis -> increase in lactate
22
Q

What is the effective yield of anaerobic glycolysis?

A
  • Net 2 ATP (total 4, but use 2 in the 1st steps)
  • 2 lactate molecules
  • Net 0 NADH (create 2 but oxidize 2 in conversion of pyruvate -> lactate)
23
Q

What is the effective yield of aerobic glycolysis?

A
  • Net 2 ATP (total 4, but use 2 in the 1st steps)
  • 2 pyruvate molecules
  • Net 2 NADH molecules (each can create about 3 ATP in ETC)
24
Q

What hormonal regulation occurs in glycolysis?

A
  • Allosteric or covalent phosphorylation (short-term)
  • Slower hormonal changes in gene expression (hours to days)
  • Insulin turns ON
  • Glucagon turns OFF
  • 1st major regulatory step: F6P -> F1,6P
  • 2nd major regulatory step: phosphoenolpyruvate -> pyruvate

Biochemistry Exam 2 (8 decks)

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