Glycolysis
glycolysis
  • Regulated steps:
    • Hexokinase: inhibited by G6P
      • Glucokinase is the liver + β islet version of hexokinase, and is not inhibited by G6P.
    • Phosphofructokinase: inhibited by ATP, low pH, NADH, citrate, long chain fatty acids. Activated by AMP, Fructose 2,6 Bisphosphate (allosteric activator). This is the rate limiting enzyme.
    • Pyruvate kinase: inhibited by acetyl-CoA, ATP, NADH. Activated by G6P, F1,6BP.
  • 2 ATP Expenditure:
    • Glucose → G6P (HK, ATP→ADP)
    • G6P ↔ F6P (PGI)
    • F6P → F1,6BP (PFK, ATP→ADP)
  • 2 NAD+ → 2 NADH
    • F1,6BP ↔ GAP + DHAP (Aldolase)
    • DHAP ↔ GAP (TIM)
    • GAP ↔ 1,3 BPG (GAPDH, NAD+→NADH)
  • 4 ATP Harvest:
    • 1,3 BPG ↔ 3PG (PGK, ADP→ATP)
    • 3PG ↔ 2PG (PGM)
    • 2PG ↔ PEP (Enolase)
    • PEP → Pyruvate (PK, ADP→ATP)
  • Occurs in the cytoplasm, can be amplified if ↑ substrate, ↓ product (exercising muscle, RBCs), ↑ F2,6BP (insulin, epinephrine).
  • Regenerating NAD+ for glycolysis:
    • Glycerol phosphate shuttle: aerobic, found in most cells with mitochondria, 2 ATP per NADH
    • Malate shuttle: aerobic, found in heart, 3 ATP per NADH
    • Lactate dehydrogenase:anaerobic, pyruvate ↔ lactate, no ATP produced, part of the Cori cycle
    • Cori cycle: lactate back to pyruvate
      • Glycolysis: glucose → pyruvate
      • Lactate DH: pyruvate → lactate
      • Liver Lactate DH: lactate → pyruvate
      • Gluconeogenesis: pyruvate → glucose
  • Hemolytic anemia (95% due to deficient PK, 4% due to PGI):
    1. Deficiencies in glycolytic enzymes.
    2. RBC (no mitochondria, depend solely glycolysis) can't get ATP .
    3. Can't maintain Na-K pump (3 Na out 2 K in).
    4. Too much salt inside RBC lead to cell lysis by osmosis.

Sugar Transporters

  • intestine → Enterocytes:
    • SGLT1: glucose and galactose (sodium cotransport)
    • GLUT5: fructose
  • Enterocytes → blood:
    • GLUT2: glucose, galactose, and fructose
  • blood → cells
    • GLUT 1 & 3: RBC, brain (don't respond to insulin, provide constant supply of glucose).
    • GLUT 2: Low affinity for glucose, acts as sensor for when blood glucose is high. Liver (high glc levels stimulate glycogen and lipid synthesis), β islet cells in pancreas (high glc levels stimulate insulin release).
    • GLUT 4: skeletal muscle (insulin or electrical stimulation causes translocation of GLUT4s to membrane), adipose (insulin causes translocation of GLUT4s).

Chemical structures

Glycolysis with structures