Glycolysis and Sugars Flashcards
Glucokinase
Liver, pancreas, gut brain only. High Km high Vmax. Induced by insulin. High glucose concentrations will lead to max glycogen storage and lipid prodcution, minimal negative feedback from glucose 6 phosphate
Hexokinase
All tissues. Low Km, Low V max. Converts glucose to glucose 6 phosphate in all tissues. Negative feedback by glucose 6 phosphate. Not effected by insulin.
Glucose 6 phosphate
Glycolysis
Glucose 1 phosphate
Glycogen
Key enzymes in glycolysis regulation
Glucokinase/hexokinase, inhibited by g6p (induced by insulin for glucokinase)
- PFK-1: F6P to F16BP. Inhibited by high energy (ATP, citrate) activated by low energy (AMP). In the liver there is PFK2 which is regulated by insulin (increased) which allows PFK-1 to run under circumstances of high energy (Liver only)
- Pyruvate Kinase, PEP to pyruvate. Inhibited by ATP and alanine (High energy inhibition) activated by F1,6BP (feedforward increase, substrate buildup)
Pyruvate Kinase Deficency
- PEP to Pyruvate
- glycolysis stops and can’t regenerate NAD from lactate (LDH and pyruvate)
- 2nd most common cause of hemolytic anemia (loss of pumps and membrane integrity). There will be no Heinz Bodies
Regulation of PFK-2
- Insulin will increase functionality by removing phosphate
- Glucagon will decrease functionality by adding a phosphate
Essential Fructosuria
- Benign condition, loss fructokinase.
- Frucotse will be present in urine
- No trapping of polyols prevents damage
- Generally presents following weaning
Fructose intolerance
- Defect in Aldolase B
- Fructose 1-P can’t be metabolized and builds up in tissues
- Most commonly seen effecting liver
- Generally presents following weaning
Fructoose and glycolysis
fructose 1 phosphate passes glucokinase and PFK so enters below 2 limiting steps (PFK bigger)
-Highest flux through glycolysis
Galactokinase Deficency
- Galactose enters cells and is converted to galacticol by aldolase
- Can’t escape, builds up.
- Neonatal cataracts
- Less severe galactose is never trapped in cells
Galactose-P-uridyl transferase deficency
- Galactose trapped in cells by galactokinase.
- Normally converted to glucose using UDP and enzyme
- Loss of enzyme leads to accumulation
- Cataracts and sever disease of liver and brain. Cirrhosis and mental retardation
Diabetic Sorbitol Damag
- Elevated glucose generates sorbitol by aldose redcutase
- Kidney, Myelin, Lens doesn’t have sorbitol dehydrogenase and so accumulates.
Pyruvate Dehydrogenase
- Located in mito
- Pyruvate to acetyl-CoA and traped in in mito
PDH Deficency
- Most common is alcoholics (lack thymine)
- Buildup of pyruvate goes to lactate leads to lactic acidosis
- Seen in alcholics and precipitated by introduction of glucose
- Congenital shows severe neuronal defects early in life (give ketogenic diet)
