Carbohydrate metabolism

Question 1

Regarding the PPP, describe the results if:

1) Requirement for NADPH exceeds requirement for Pentose-P in biosynthesis
2) Requirement for pentose-P exceeds rate of oxidation rxns
3) Pentoses are available in excess in diet

Answer 1

1) Excess pentose-P is converted to glycolytic intermediates and metabolized
2) Pentose-P needs are met by conversion of F6P and GAP to pentose-P via transketo/aldolase
3) pentoses are converted to ribose5P and then to F6P/GAP

Question 2

Where is Glucose 6 Phosphatase found as opposed to the other gluconeogenic/glycolytic enzymes?

Answer 2

lumenal side of the ER.

NOTE: Pyruvate Carboxylase makes OAA from pyr in the matrix, which becomes Malate via MDH, and then Malate is transported into the cytosol, and converted back to OAA and PEP carboxykinase is used in the cytosol to make PEP from OAA.

Question 3

Metformin is one of the most widely prescribed drugs. What does it do?

Answer 3

It indirectly inhibits FBPase1 which is prescribed for diabetes mellitus patients. It inhibits ATP production in electron transport (by inhibiting NADH-CoQ reductase (complex I)), thus elevating AMP levels which inhibit FBPase1.

Question 4

What do the following disease affect and how are they presented?
1)Anderson’s disease

2) Cori’s Disease
3) Her’s Disease
4) McArdle’s Disease
5) Von Gierke’s Disease

Answer 4

1) Anderson’s disease:branching enzyme (liver,spleen); normal amt of glycogen but very long branches, progressive liver cirrhosis, early death
2) Cori’s Disease: debranching enzyme (muscle,liver); Short outer branches in glycogen, hepatomegaly, cardiomegaly, hypoglycemia
3) Her’s Disease: liver glycogen phosphorylase; hepatomegaly, inc glycogen, mild hypoglycemia (can use gluconeogenesis)
4) McArdle’s Disease: Muscle glycogen phosphorylase; inc in m. glycogen, fasting glc lvls in blood, exercise induces painful cramps, low lactate accumulation during exercise

​5)Von Gierke’s Disease: Glc-6Pase; severe fasting hypoglycemia w/ elevated lactate and pyr, hepatomegaly, excess glycogen, defects in carriers transporting G6P across ER membrane have similar phenotypes