Pentose Phosphate Pathway

Which type of fructosemia is worse and why?

F1P-aldolase loss-of-function bc it traps F1P in the liver

How do fructosemic patients clear out fructose?

Via other tissues than the liver (muscle+hexokinase)

What is sucrose made of?

Glucose-Fructose dimer

How can fructosemic patients process milk’s main sugar?

Like normal subjects (galactose-glucose dimer)

Why can only Type I and II galactosemic mothers produce milk?

Bc type III includes the enzyme that is needed in the inverted reaction that allows them to make galactose from glucose

How is the energy needed to invert the epimerase reaction obtained?

From PP_i→2 P_i from UDP-glucose formation

What are the 3 main pathways used by the liver?

1. Glycogen synthesis and breakdown

2. TG + ATP synthesis from CAC

3. PPP

What is the raison d’être of PPP?

When dividing cells need a lot of nucleotides (DNA) as well as phospholipds and triglycerides (membrane)

Where does the PPP branch off and back in?

At G6P back into F6P and GAP

What is the committing enzyme of the PPP?

G6PDH

What is the output of the PPP?

R5P and NADPH

What is the difference between NADH and NADPH in terms of origins?

Glycolysis-CAC vs PPP

What is the difference betweenn NADH and NADPH in terms of metabolic uses?

ATP productionn (ox. phos.) vs Fatty acid, cholesterol biosynthesis

What is the difference between NADH and NADPH in terms of cytosolic concentration of the ionized/non-ionized version?

1000:1 vs 1:100

How important is NADPH in lipid synthesis?

2 NADPH needed per FA

What is R5P used for?

It is needed for nucleotide biosynthesis as its backbone

Purpose of the oxidative phase of the PPP

NADPH production

Gluc:NADPH in oxidative reactions of the PPP

1:2 (times 3)

How does NADPH act as a modulator for G6PDH?

Strong allosteric inhibitor

First part of the non-oxidative reactions

Isomerization (1) and epimerization (2) of Ru5P (3 total)

What are the rest of the non-oxidative reactions named?

Recycling reactions

How is the fate of G6P decided?

Depending on the body’s needs in ATP, NADP and R5P

What if the body needs NADPH and R5P?

It will run the PPP while excess R5P and Ru5P will be recycled

What if the body only needs NADPH?

It will run the PPP

Whta if the body only needs nucleotides?

Reversal of transaldolase and transketolase reactions bc the forward reaction would be inhibited by NADPH

What do cancer cells disturb in the PPP?

Increase transcription if G6PDH = more NADPH which will eventually inhibit it

What is G6PDH deficiency?

Common enzymopathy characterized by the loss of G6PDH efficiency due to breakdown of the mutant enzyme

Clinical manifestation of G6PDH deficiency

Hemolytic anemia with jaundice