Glucose Pathways
Where is glucokinase found? What is the Km and Vmax of glucokinase relative to hexokinase?
Found in liver and pancreatic beta cells.
Higher Km (lower affinity)
Higher Vmax
How does glucose enter and exit intestinal epithelial cells?
Glucose enters the epithelial cells via SGLT1 receptors that co-transport Na+ and glucose into the cell using Na+ traveling down its concentration gradient to move glucose
Glucose (along with fructose and galactose), can diffuse through GLUT2 transporters into the blood stream.
What caused Baby Albert to have seizures?
Hypoglycemia. The brain is glucose-dependent and has low glycogen stores.
Massive cascades of axon depolarization caused by failure of Na/K pump and accidental release of excitatory neurotransmitters (NT)
What is the difference between GSD 1a and 1b? How did the detergent test help us narrow down between the two?
1a: G6Pase deficiency
2a: G6PT deficiency
Without detergent: pyrophosphatase activity but no G6Pase activity.
With detergent: G6Pase activity is restored and pyrophosphate activity is maintained. Detergent disrupts membranes, so this test reveals that glucose-6-phosphatase is functional but that the T1 transporter is not (confirms GSD Ib)
What enzyme is deficient in GSD V (McArdle's), and what are the symptoms?
Deficiency in myophosporylase
Muscle cannot break down glycogen. Get painful muscle cramps, myoglobinuria (red urine) with strenuous exercise
How did dysfunctional glucose metabolism cause lactic acidosis in Albert?
Because G6P cannot be converted to glucose, G6P will be shunted to different pathways. In a hypoglycemic state, G6P will go through glycolysis, increases the amount of pyruvate, which will turn into lactic acid by LDH.
Ceftriaxone inhibits this enzyme in bacterial cells
What is Transpeptidase (a penicillin-binding-protein)
Why was Baby Albert positive for ketones and have a high level of triglycerides?
Without glucose, his muscles were using ketones for energy
Glucagon is activating release of triglycerides from fat stores to promote beta oxidation and gluconeogenesis (which will not be effective at restoring blood glucose in GSD I)
What are the roles of the G6PT1, G6PT2, and G6PT3?
T1 lets G6P into the ER to be dephosphorylated by G6Pase.
T2 is a bidirectional phosphate channel.
T3 lets glucose back out into the cytoplasm.
Which enzyme is deficient in GSD II and what are the symptoms?
Pompe's Disease.
Lysosomal a-1,4-glucosidase (acid maltase). Impaired glycogen breakdown. Causes cardiomyopathy, hypotonia, exercise intolerance