HBIO302 - Pentose Phosphatae Pathway and Fructolysis

The pentose pphosphate pathway (PPP) is also known as..

hexose monophosphate shunt

Where does the PPP occur and what pathway does it run parallel to?

cytosol; glycolysis

There are two phases of PPP. These are:

oxidative and non-oxidative

Products of PPP

NADPH and R5P (ribose-5-phosphate)

Where are PPP enzymes highly expressed

where high lipid biosynthesis takes place, like in the liver and adipose tissue

30% of glucose oxidation in the liver occurs via..

PPP, not glycolysis

No ATP is directly consumed or produced by this pathway

true

PPP Oxidative Phase Step 1 Role

G6PD reaction, rate limiting step, converting G6O to 6-PGDG, reducing NADP to NADPH

What is an inhibitor of G6PD?

NADPH

The oxidative phase of the PPP consists of 3 ____ reactions

true

Products of PPP oxidative phase

Ru5P, CO2, 2NADPH for each molecule of G6P oxidized

PPP Oxidative Phase Step 2 Role

6PGDH role, Converts lactone to an open-ring structure, preparing it for decarboxylation

PPP Oxidative Phase Step 3 Role

6PGD reaction, Generates a second NADPH and releases CO2, yielding Ru5P

Ru5P is a precursor for the synthesis of these compounds

nucleotides

NADPH is used in…

reductive biosynthetic rxns, or anabolism

NADH (NAD+) is used in..

it donates e- to the ETC, or catabolism

What are the functions of NADPH?

Reductive biosynthesis, H2O2 reduction, detoxification via cytochromes, destruction of microorganisms by WBCs, and nitric oxide synthesis

What pathways require NADPH as an e- donor?

FA synthesis, cholesterol synthesis, and steroid hormone synthesis

How does NADPH indirectly provide e- for the reduction of H2O2?

oxidized gluthione is regenerated by gluthione reductase using NADPH

How does NADPH provide the electrons required by cytochromes to hydroxylate toxins?

inactivating them and increasing their solubility and therefore excretion

How does NADPH contribute to the destruction of pathogens by WBCs?

after phagocytosis, NADPH oxidase converts oxygen to superoxide (O2-) which is converted to H2O2

So it generates O-derived free radicals that kill bacterium

How is nitric oxide a mediator in different biologic systems?

causes vasodilation by relaxing smooth muscle

neurotransmitter

macrophase function (ROS)

prevents platelet aggregation

Why does NO have a super short half-life?

it reacts with oxygen/superoxide and gets converted into NO3 and NO2

Types of NO synthases:

endothelial - eNOS

Neuronal - nNOS

induciblee - iNOS

PPP nonoxidative phase step 1

Ru5P isomerase; converts Ru5P to R5P, used for nucleotide and nucleic acid biosynthesis

PPP nonoxidative phase step 2

transketolase and transaldolase reactions

The enzymes in the non-oxidative phase of the PPP enable the production of..

2 F6P and 1 G3P which are used for glycolysis

This compound is the key regulator of PPP via this feedback loop.

G6PD; negative NADPH feedback loop

Insulin ____ G6PD gene expression, while Glucagon ____ it

enhances; reduces

If a cell needs NADPH > R5P

R5P is converted by transketolase and transaldolase into G3P and F6P as glycolytic intermediates → eventually ATP

If a cell needs R5P > NADPH

G3P and F6P exit glycolysis pathway and enter non-oxidative part of PPP to provide R5P w/o producing NADPH

Free ribose is very low. Why?

Most of the ribose is tied in more complex molecules such as nucleotides and ATP

Nucleic acids and ATP are digested in the _____

small intestine, with help of pancreatic and intestinal enzymes

How is ribose absorbed?

SGLT-1 by entereocytes and different GLUTs in other tissues

Ribose is phosphorylated by this enzyme to R5P which then enters this part of the PPP

ribokinase; non-oxidative part of PPP

Dietary ribose plays a minor role in endogenous pentose metabolism

true

Ribose supplements effects

Boosts ATP lvls ad accelerates ATP recovery/resynthesis

How does ribose boost ATP levels?

it is the backbone sugar of ATP; additional source of ribose = more available for nucleotide and ATP synthesis

More ATP in muscle as well as faster recovery from ATP depletion leads to…

more power/endurance and less soreness

Clinical studies of ribose supplements suggest that..

they can inc exercise capacity in heart patients, leading to hypothesis that it could improve athlete performance

Ribose supplementation is not really needed

true

G6PD deficiency (favism)

significant reduction in NADPH; affects RBCs the most as the PPP is the only way they produce NADPH.

acute hemolytic anemia in response to fava beans or infections (generate oxidizing agents)

What happens when RBCs do not have NADPH?

they can no longer defend against the constant introduction of oxidizing agents (shorter RBC half-life)

Where is the oxidative portion of PPP important?

liver, adrenal cortex, RBCs, immune cells

Dietary fructose CANNOT enter the PPP

true

Fructose can be metabolized to intermediates that feed into glycolysis which in turn connects to the PPP

true

Left off on Fructose Metabolism - Fructolysis slide