Pentose Phosphate Pathway

Question 1

Pentose Phosphate Pathway

Answer 1

The purpose of the pathway is to generate NADPH (reducing power) and 5-carbon sugars

Question 2

What are the 5-carbon sugars used for?

Answer 2

Nucleotide biosynthesis

Question 3

What is NADPH used for?

Answer 3

1. Used in fatty acid synthesis, nucleotide biosynthesis, steroid synthesis
2. NADPH detoxifies some compounds for us

Question 4

Phase 1 of pentose phosphate pathway (oxidative step)

Answer 4

Glucose 6-Pi + 2 NADP+ + H2O –> ribulose 5-Pi + 2 NADPH + 2 H+ + CO2

Glucose is oxidatively decarboxylated to form a 5-carbon ketose, generating NADPH and CO2

Question 5

Phase 2 of pentose phosphate pathway (non-oxidative step)

Answer 5

Interconverts sugars among each other. Non-oxidative because no NADPH is produced.

3 ribulose 5-phosphate sugars are rearranged to yield 2 fructose-6-Pi and 1 glyceraldehyde-phosphate. The net reaction is the conversion of three pentoses into two hexoses and one triode.

“3 ribs 2 form 1 gal”
3 ribose-5-P –> 2 fructose-6-P + glyceraldehyde-3-P

Question 6

Glucose 6-phosphate dehydrogenase

Answer 6

The enzyme that catalyzes the first step in the oxidative decarboxylation of glucose 6-Pi.

Question 7

Regulation of non-oxidative phase

Answer 7

Le Chatelier only

Question 8

The Fate of Glucose 6-Pi

Answer 8

Depends on the need for NADPH, Ribose 5-Pi, and ATP

The pentose phosphate pathway can operate in 4 distinct modes that result from various combinations of the oxidative phase, the non oxidative phase, glycolysis, and gluconeogenesis.

1. Ribose 5-Pi needs exceed the needs for NADPH (there’s a high need for ribose during cell division)
2. The NADPH and ribose 5-Pi needs are balanced
3. More NADPH is needed than ribose 5-Pi
4. NADPH and ATP are both required

Question 9

Case 1: Need more ribose than NADPH

Answer 9

We would run the non-oxidative stage backwards. We need 2 molecules of fructose-6-Pi and 1 molecule of glyceraldehyde-Pi to make ribose. We can get both from the forward reaction of glycolysis.

Question 10

Case 2: We need ribose and NADPH

Answer 10

Any time we need NADPH, we have to run the oxidative phase. The oxidative phase will give us 2 molecules of NADPH and 1 molecule of ribulose, which can be converted easily to ribose.

Question 11

Case 3: We need more NADPH than ribose

Answer 11

Again, we need to run oxidative phase to generate NADPH. We could also run non-oxidative phase forward to generate fructose-6-Pi and glyceraldehyde-Pi

Question 12

Case 4: NADPH and ATP are both needed

Answer 12

Run oxidative phase to generate NADPH. Then run oxidative phase to get fructose-6-Pi and glyceraldehyde-3-Pi, which we can funnel into glycolysis to generate ATP.

Question 13

Regulation of pentose phosphate pathway

Answer 13

• -Non-oxidative phase is only regulated by Le Chatelier
• -Oxidative phase regulation:
  1. glucose 6-phosphate dehydrogenase step, the first in the pathway, is the rate-limiting step. It is also the committed step. Once you decarboxylate glucose-6-Pi, you can’t go back.
  2. If NADP+ is in short supply, the pathway cannot run. If you are doing a lot of synthetic reactions, NADP+ would be high in concentration. NADPH competes for the binding site. So if NADPH is high and NADP+ is low, pentose phosphate pathway is inhibited

Question 14

Tissues using NADPH

Answer 14

adrenal glands - steroid synthesis
liver - fatty acid and cholesterol synthesis
testes- steroid synthesis
adipose tissue - fatty acid synthesis
ovaries - steroid synthesis
mammary glands - fatty acid synthesis
red blood cells - maintenance of reduced glutathione

Question 15

Red blood cells use of NADPH

Answer 15

RBC’s are exposed to a lot of oxidations circulating in the blood, so they have a mechanism to neutralize strong oxidation agents using a molecule called glutathione. Glutathione becomes oxidized instead of your proteins or lipids in the membrane and then to get it reduced again so it can do another reaction, NADPh is used.

Question 16

Where is pentose phosphate pathway located?

Answer 16

cytoplasm

Question 17

Glutathione

Answer 17

In its reduced form, it’s composed of 3 amino acids linked together (glutamate, cysteine, glycine). The thiol group on cysteine is what is oxidized.

Oxidized glutathione: 2 chains of these amino acids are hooked together by a disulfide bond, which occurs when glutathione is oxidized.

Glutathione must be reduced by NADPH again so it’s available to deal with reactive oxygen species such as peroxides again.

Question 18

hemolytic anemia

Answer 18

Occurs when glutathione is lacking in red blood cells. The hemoglobin tends to aggregate, forming Heinz bodies.

Lack of glucose-6-Pi dehydrogenase makes it even more difficult to have functioning glutathione.

Question 19

Evolutionary advantage of lack of glucose-6-Pi

Answer 19

Glucose-6-Pi dehydrogenase deficiency protects against malaria by depriving the parasites of NADPH that they require for growth.