G6PDHase Deficiency
GLYCOLYSIS
Glucose
ATP
Hexokinase (low Km)
Glucokinase (high Km)
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X-Linked disorder (4x106 affected)
Associated w/fava beans
GSSG + NAPDH  GSH + NADP+
↓ GSH  ↑ oxidative damage
Hexose monophosphate
ADP
NADP+
G-6-P
Glycogen
G6PDHase
ATP
NADPH
F-6-P
Pentose monophosphate
Phosphofructokinase-1 (PFK-1)
*COMMITTED Step
ADP
F-1,6-bP
Continued…
G-3-P
Enzyme Regulation
• Hexokinase: All cells; Low Km
• Glucokinase: Hepatocytes; High Km
• PFK-1: COMMITTED STEP
DHAP
F-1-P
Fructose
Continued…
Arsenic Poisoning
G-3-P
PO43- + NAD+
• AsO43- analogous to PO43• Replaces PO43- in GAPDHase rxn
• Decreases ATP synthesis
Glyceraldehyde-3-Phosphate (G3P) Dehydrogenase
NADH
1,3-bPG
ADP
2,3-bPG
Phosphoglycerate (PG) Kinase
*Hb-O2 Regulator
ATP
3-PG
PO43_
Hypoglycemia, acidemia, and NaF
2-PG
Enolase
Pyr-Kinase Deficiency
• Autosomal recessive
• Hemolytic anemia b/c
RBCs dependent on
anaerobic respiration
PEP
ADP
Pyruvate Kinase
ATP
Pyruvate
• RBCs anaerobically dependent
• False hypoglycemia & acidemia
w/blood draws common
• NaF added to blood sample…
• Enolase inhibited by F- ion
GLYCOLYSIS
Fates of Pyruvate
Product
Enzyme
Function
Lactate
Lactate dehydrogenase
Anaerobic pathway; regenerate NAD+
Acetyl-CoA
Pyruvate dehydrogenase complex
TCA Cycle entry
Oxaloacetate
Pyruvate carboxylase
TCA Cycle replenishment
Alanine
Alanine transaminase
Amino-group carrier (to liver)
Pyruvate Dehydrogenase Complex (PDC)
• 3 Enzymes
• 5 Co-Factors: Vitamin B1,2,3,5 and Lipoic acid