Pentose Phoshate Shunt & Gluconeogeneses*

Question 1

Describe the steps involved in the Pentose Phosphate Pathway with regards to the irreversible oxidative phase and the reversible nonoxidative phase, and the enzymes that participate in each

Answer 1

See pg. 94-95 & 108

Pentose phosphate occurs in the cytosol & yields NADPH and ribose-5-phosphate (R5P)

Question 2

Explain how any combination of the useful products of the pathway (NADPH and ribose- 5-phosphate) can be generated by altering the flux of molecules through the oxidative and nonoxidative phases

Answer 2

If we need ribose but not NADPH, we can run the nonoxidative phase of the Shunt in reverse, starting with F6P and GAP and ending with R5P

If the cell needs both NADPH and ribose, we can get two NADPH/ribose if we run just the oxidative phase of the Shunt and convert all of the Ru5P produced to R5P

Question 3

List the uses of the products of the pathway

Answer 3

Products = NADPH and ribose-5-phosphate (R5P)

If we start with three Glucose (18 carbons), the oxidative phase yields three CO2 (3 carbons), three Ribulose5P (15 carbons), and six NADPH.

We need ribose for information storage (RNA/ DNA), energy transfer (ATP), oxidation/reduction reactions (NADH & FAD), and enzyme catalysis (CoA).

Question 4

Describe how three Bypasses to the Glycolytic Pathway allow pyruvate, oxaloacetate, and their precursors in the mitochondrial matrix to be used to generate new glucose in the cytosol (Gluconeogenesis).

List the names of, and reactions catalyzed by, the Bypass enzymes.

Answer 4

AA, Acetyl CoA, & Lactate bypass glycolysis to become pyruvate–which can be reversed to glucose to create new glucose when glycogen stores are low = gluconeogenisis.

Three of the four kinase reactions of glycolysis are irreversible. The three Bypasses provide thermodynamically favored alternative steps.

Bypass 1. Pyruvate carboxylase + PEPCK; opposite of pyruvate kinase. Pyruvate becomes Phosphoenol pyruvate.
- In the second reaction, catalyzed by PEP carboxykinase, the recently acquired carboxylate group of Oxaloacetate is released as CO2 to generate the enolate form of pyruvate which can be phosphorylated by GTP to give PEP (phosphoenol pyruvate which becomes 2 Phosphoglycerate). There is no transport system for OAA, but it can exit mito by the Mal/Asp shuttle running in reverse after first being reduced to malate. It is then converted back to OAA in the cytosol. Human mitochondria contain PEPCK, and there is a PEP transporter.

Bypass 2. FBPase; opposite of PFK. 1,6FBP becomes F6P.

Bypass 3. Glucose-6 Phosphatse; opposite of Hexokinase. In liver only! G6P becomes Glucose.

Glycolysis and Gluconeogenesis are reciprocally regulated to avoid a futile cycle.

Question 5

Describe how the Cori Cycle works and what its purpose is

Answer 5

• When ATP demands in muscle exceed the capacity of Ox Phos for generating ATP, lactate is produced (also in RBC which lack mitochondria)
• The lactate is carried to the liver where it is converted to Glu via Gluconeogenisis and released back into the bloodstream
• This process is called the Cori Cycle
• After exercise this continues as muscle glycogen stores are replenished

• The amount of O2 consumed in liver during this rebuilding of muscle glycogen is called
the “Oxygen Debt”

Question 6

Discuss G6PDH Deficiency

Answer 6

G6PDH Deficiency:

> 400 mil people
Most common human enzyme deficiency

Consequenses: Favism (Hemolytic anemia)
Selective advantage where malaria is endemic

• Individuals with G6PDH deficiency experience hemolytic anemia when they take antimalarial drugs such as quinine or chloroquine
• Evolutionary advantage: it’s better to pay the metabolic cost of a faster rate of turnover of RBC’s than to die from malaria

A. It is the most common human enzyme deficiency
B. It has a selective value where malaria is endemic
C. It can lead to hemolytic anemia upon ingesting fava beans