Carbohydrate Metabolism Flashcards
What are the products of glycolysis?
2 ATP, 2 NADH, and 2 Pyruvate
How is GLUT 4 activated?
Insulin binds to insulin receptor in membrane, activating vesicles containing GLUT4 to bind to membrane and let glucose in.
What is the rate limiting enzyme in glycolysis?
Phosphofructokinase-1 (PFK-1)
What are the 3 irreversible phosphorylation steps of glycolysis?
- Hexokinase/Glucokinase
- Phosphofructokinase-1
- Pyruvate kinase
What is hexokinase (HK) inhibited by?
G6P, its product
How is glucokinase (GK) inhibited?
F6P promotes relocation to the nucleus where it cannot act on glycolysis. High glucose levels relocate it out of the nucleus.
What is PFK-2’s role in glycolysis regulation?
When recently fed, it will create F2,6BP from F6P which will activate PFK-1.
What is Tarui disease?
Deficiency in PFK-1.
Symptoms: muscle cramps/weakness, jaundice, hemolytic anemia
What is cAMP’s role in pyruvate kinase (PK) regulation?
High glucagon increases concentration of cAMP which phosphorylates and inhibits PK.
What are the clinical markers for hemolytic anemia?
Elevated lactate dehydrogenase and unconjugated bilirubin because these are released from RBCs when they are lysed.
What is Fanconi-Bickel syndrome?
Mutation in GLUT 2 transporter. Unable to take up glucose, fructose, and galactose in liver/pancreas.
Symptoms: failure to thrive, hepatomegaly, abdominal bloating, rickets.
What are the precursor molecules for gluconeogenesis?
Fructose, galactose, glycogen, glycerol, propionate, lactate, alanine, amino acids
What is the rate limiting enzyme of gluconeogenesis?
Fructose 1,6-biphosphatase
What enzyme in gluconeogenesis is only found in the liver, kidney’s, and pancreas?
Glucose 6-phosphatase
What enzymes in gluconeogenesis “bypass” the irreversible steps of glycolysis?
- Pyruvate carboxylase and PEP carboxykinase bypass pyruvate kinase
- Fructose 1,6 biphosphatase bypasses PFK-1
- Glucose 6-phosphatase bypasses hexokinase/glucokinase
What is the cofactor for pyruvate carboxylase?
Biotin
How is G6P converted to glucose?
G6P is brought to glucose 6-phosphatase, which is located in the lumen of the ER (liver, kidneys, and pancreas only). Glucose 6-phosphatase consists of a catalytic unit, an antiporter, and a GLUT7 so glucose and be transferred back to the cytoplasm.
What is F1,6BP deficiency?
A deficiency in the rate-limiting enzyme of gluconeogenesis.
Symptoms: hypoglycemia, lactic acidosis, ketosis
What is Von Gierke disease/GSD1a?
Deficiency in glucose 6-phosphatase, the last step of gluconeogenesis.
Symptoms: fasting hypoglycemia, lactic acidosis, hepatomegaly due to buildup of glycogen, hyperlipidemia
Describe the Polyol pathway.
It is the process by which glucose is converted to fructose. First, glucose is reduced to sorbitol by Aldose reductase. Then, sorbitol is oxidized to fructose by Sorbitol dehydrogenase.
What leads to sorbitol accumulation and what are the symptoms?
Occurs in cells that lack sorbitol dehydrogenase (Polyol pathway).
Symptoms: swelling, retinopathy, cataracts
How is fructose metabolism different than glucose metabolism?
Fructose metabolism is faster and bypasses the rate limited step (PFK-1) of glycolysis. Can lead to excess fatty acid formation.
What is the rate-limited enzyme of galactose metabolism?
Glucose 1P uridyltransferase (GALT)
What are the two main types of Galactosemia and their associated symptoms?
- Deficiency in GALT (classic galactosemia) leads to accumulation of galactitol. Symptoms: failure to thrive, liver failure.
- Deficiency in galactokinase (nonclassical galactosemia) leads to the accumulation of galactitol. Symptoms: cataracts in early infancy.
What is the role of glutathione?
Antioxidant, detoxifies H2O2
Where in the body is there high demand for PPP?
Lactating mammary glands, lung/liver tissue, and phagocytic cells.
On what end is glycogen both degraded and extended?
From the non-reducing end
What protein is attached to the reducing end of glycogen?
Glycogenin
Describe G6PD deficiency.
PPP cannot proceed, leading to low NADPH levels. Common in African population.
Symptoms: hemolytic anemia.
What does Glycogen phosphorylase (GP) use as a cofactor?
Pyridoxal phosphate (vitamin B6)
How is glycogen synthase and glycogen phosphorylase regulated?
Glycogen synthase is activated in the dephosphorylated form. Glycogen phosphorylase is activated in the phosphorylated form.
Describe how insulin activates glycogen synthesis.
Insulin binds to insulin receptor which activates PKB and translocates GLUT 4 to the plasma membrane. PKB activates PP1 and inactivates GSK3.
What is GSD 0?
Deficiency in glycogen synthase. Rely on glucose in diet.
What is Pompe disease/GSD II?
Deficiency in Acid Maltase aka acid alpha-glucosidase. Impairs lysosomal glycogenolysis, resulting in accumulation of glycogen in lysosomes.
What is Cori Disease/GSD III?
Deficiency in alpha-1,6-glucosidase (debranching enzyme). Leads to glycogen molecules with large number of short branches.
What is Andersen disease/GSD IV?
Deficiency in glucosyl (4:6) transferase (branching enzyme). Patients have long glycogen chains with fewer branches. Death by 5 years of age.
What is McArdle disease?
Deficiency in muscle glycogen phosphorylase. Unable to supply muscles with enough glucose.
What is Hers disease/GSD VI?
Deficiency in liver glycogen phosphorylase. Leads to hepatomegaly.
What does glycogen phosphorylase use as its cofactor?
Pyridoxal phosphate (vitamin B6)
