M4 - Glycolysis, TCA Flashcards
Overall Reaction: Glycolysis
- 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
“Opposing” Pathways
Glycolysis vs. Gluconeogenesis
7 of the glycolytic enzymes are reversible and are also gluconeogenic enzymes
Transport of Glucose
- Glucose Transporters (GLUTs)
- Sodium-Glucose Co-Transporters (SGLTs)
GLUT2
-constitutively expressed
-liver, pancreatic beta cells
GLUT4
-regulated by insulin
-skeletal muscle, fat
SGLT2
-Proximal tubule
-Saturates with hyperglycemia = glucosuria, polyuria
-Target for diabetes mellitus treatment drug class (-gliflozin)
Simplified Glycolysis Pathway, Three Key Enzymes
-Glucokinase or Hexokinase
-Phosphofructokinase-1 (PFK-1)
-Pyruvate Kinase (PK)
- Irreversible
- Regulated
- Use/Produce ATP
Mechanisms to Regenerate NAD+
Shuttles to transport reducing “equivalents”
The two major shuttles:
1. Glycerol 3P Shuttle
2. Malate-Aspartate Shuttle
Factors that increase lactate production:
- mitochondrial dysfunction
- low cellular O2
- cancer cells
- metformin
Normal lactate production occurs by cells lacking ___
mitochondria
Reduction of pyruvate to lactate via ___
LDH
NADH and FADH2 ____ electrons to the ETC
DONATE
OAA is made from ___ during gluconeogenesis
pyruvate
Thiamine Deficiency
Leads to
1. Wernicke-Korsakoff syndrome (ataxia, mental state, ophthal)
2. Beriberi (polynuero/HF)
In patients with critically low thiamine levels, administration ____ can cause or worsen Wernicke-Korsakoff syndrome
Glucose
-In ER, administer thiamine prior to or along with glucose infusion, especially those at risk (e.g., chronic alcohol use)
