M4 - Glycolysis, TCA

Question 1

Overall Reaction: Glycolysis

Answer 1

• 2 pyruvate molecules produced
• Net 2 ATPs produced
• NADH must be oxidized to NAD+ to keep glycolysis going
• Mechanism of NADH oxidation and fate of pyruvate
  depend on cellular conditions

Occurs in all cells, cytosol

Question 2

“Opposing” Pathways

Answer 2

Glycolysis vs. Gluconeogenesis

7 of the glycolytic enzymes are reversible and are also gluconeogenic enzymes

Question 3

Transport of Glucose

Answer 3

• Glucose Transporters (GLUTs)
• Sodium-Glucose Co-Transporters (SGLTs)

Question 4

GLUT2

Answer 4

-constitutively expressed
-liver, pancreatic beta cells

Question 5

GLUT4

Answer 5

-regulated by insulin
-skeletal muscle, fat

Question 6

SGLT2

Answer 6

-Proximal tubule
-Saturates with hyperglycemia = glucosuria, polyuria
-Target for diabetes mellitus treatment drug class (-gliflozin)

Question 7

Simplified Glycolysis Pathway, Three Key Enzymes

Answer 7

-Glucokinase or Hexokinase
-Phosphofructokinase-1 (PFK-1)
-Pyruvate Kinase (PK)

• Irreversible
• Regulated
• Use/Produce ATP

Question 8

Mechanisms to Regenerate NAD+

Answer 8

Shuttles to transport reducing “equivalents”
The two major shuttles:
1. Glycerol 3P Shuttle
2. Malate-Aspartate Shuttle

Question 9

Factors that increase lactate production:

Answer 9

1. mitochondrial dysfunction
2. low cellular O2
3. cancer cells
4. metformin

Question 10

Normal lactate production occurs by cells lacking ___

Answer 10

mitochondria

Question 11

Reduction of pyruvate to lactate via ___

Answer 11

LDH

Question 12

NADH and FADH2 ____ electrons to the ETC

Answer 12

DONATE

Question 13

OAA is made from ___ during gluconeogenesis

Answer 13

pyruvate

Question 14

Thiamine Deficiency

Answer 14

Leads to
1. Wernicke-Korsakoff syndrome (ataxia, mental state, ophthal)
2. Beriberi (polynuero/HF)

Question 15

In patients with critically low thiamine levels, administration ____ can cause or worsen Wernicke-Korsakoff syndrome

Answer 15

Glucose

-In ER, administer thiamine prior to or along with glucose infusion, especially those at risk (e.g., chronic alcohol use)

Question 16

Glycolysis Regulation

Answer 16

• Irreversible steps are regulated
  -Glucokinase, PFK-1, PK
• Mechanisms of regulation
  -Allosteric
  -Hormonal (covalent modification, transcription)

Question 17

F2,6 BP - Important Allosteric Regulator

Answer 17

• Levels determined by a *PFK-2/FBPase-2
• Allosterically activates PFK-1
• Allosterically inhibits FBPase-1 (gluconeogenesis)

Question 18

Regulation PFK-2/FBPase-2 by PKA

Answer 18

Decreases F2,6 BP
-Decrease glycolysis and increase gluconeogenesis

Question 19

Regulation of PFK-2/FBPase-2 by AMPK

Answer 19

Increase F2,6 BP
-Increase glycolysis, decrease gluconeogenesis

Metformin = increases AMPK activity

Question 20

TCA Cycle

Answer 20

-Occurs in the mitochondria
-Generates 3 NADH, 1 FADH2, and 1 GTP
-NADH and FADH deliver electrons to ETC

Question 21

Glycolysis Neumonic for Intermediate Products

Answer 21

GROSS - Glucose
GUYS - G6P
FAVOR - F6P
BIG BUTTS - F16 BIPHOS
GOOD - GLY3P
BOYS - 13 BISPHOSGLY
PREFER - 3PHOSGLY
PRETTY girls in - 2PHOSGLY
PINK - PHOSPHOENOL
PJs - PYRUVATE