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Whats an overview of the functions of the Pentose Phosphate Pathway (PPP)?

1. For oxidation of glucose that synthesizes NADPH and pentose phosphates , which are 5 carbon sugars for nucleotide synthesis
2. PPP branches from glycolysis after the formation of glucose 6-phosphate; alternate pathway someones called hexose monphosphate shunt
3. All the enzymes involved in the pentose phosphate pathway are localized to the cytosol


Why is it important to use the PPP?

1. Produces NADPH
2. Produces the 5 ribose-5-phosphate a 5 carbon sugar of nucleotides


What are the differences of NADPH from NADH?

1. NADH is involved in ATP generation
2. NADPH provide reducing equivalents for rxns like fatty acid synthesis and cholesterol synthesis, happen in cytosol
3. NADPH can not be extracted for ATP
4. NADPH is necessary for regeneration of glutathione (helps gets ride of 10% metabolized APAP)


What is glutathione?

Big part of our bodies detoxification system

Has a sulfur group which allows it to bind to free radicals and toxins and neutralizes them

Once it binds to them it carries them into the bile and stool to be taken out of the body

Healthy amounts of this prevents aging, cancer, heart disease, etc


What is glutathione composed of?

Simple molecule that is made up of three amino acids
Cysteine - gives the sulfur

**poor diet or heavy drinking leads to less of this can lead to issues with health


What is NADPH a essential cofactor for?

The regeneration of glutathione


How is NADPH involved with Cytochrom p450s?

The most common rxn catalyzed by CYP450s is insertion of an oxygen into the aliphatic position of an organic substrate to increase the solubility for excretion

**NADPH i needed for this to happen


Which tissues is the pentose phosephate pathway active?

1. the enzymes for the PPP are present in all cells, but their expression varies tissue to tissue
2. High lvls of PPP enzymes are found in the liver where large amounts of fatty acids and cholesterol are synthesized, also in endocrine glands which synthesize cholesterol and steroid hormones
3. PPP is also found in cells of the early embryo and other rapidly dividing cells, which require large amounts of ribose 5-phosphate for nucleic acid synthesis


Is the PPP active in phagoctes?

Yes, its highly active in neutrophiles and macrophages

**NADPH plays a role to generate superoxide radicals from molecular oxygen
the superoxid kills bacteria


What is the oxidative phase of the PPP?

The first of three rxns.
Glucose 6-phosphate dehydrogenase catalyzed the initial oxidation of glucose 6-phosphate to 6 phosphoglucono-d-lactone

***this is the first step and is very highly regulated


What is the third step of the PPP?

Ribulose 5-phosphate is the product, CO2 is a byproduct, and a second molecule of NADPH is produced


What is the PPP oxidative branch?

Its the end of the oxidative phase, it starts with glucose 6-phosphate and you get a gain of 2 NADPH, lose a CO2 and the end product is a ribulose 5P (which can be turned into a ribose 5-P and be used in DNA/RNA)


What is the nonoxidative branch of the PPP?

Involves reshuffling of the carbon skeletons to interconvert pentose phosphates and hexose phosphates

**major enzyme of this is transketolase (must have same cofactors as pyruvate dehydrogenase complex)


What are the cofactors of transketolase?

1. TPP: thiamine prosthetic group (vit B1)
2. Lipoic acid : prosthetic group
3. CoA: comes from pantothenic acid (vit B5)
4. FAD: from riboflavin (vit B2)
5. NAD: nicotinic acid (B3)

***arsenic inhibits transketolase


What are the net reactions for of the non-oxidative branch?

you start with 3 five carbons and end with 2 six carbons and 1 three carbon

Get fructose 6-P and glyceraldehyde 3-P which return to glycolysis


What is the starting material for the PPP?

Glucose 6-Phosphate


What is an alternative way to produce NADPH?

Cells like neutrophil and heptocyte have an alternative pathway for creating NADPH

**must have malic enzyme which catalyzed the rxn
***If the cell does not have mitochondria it will lack this alternative source of NADPH since the source of malate is mitochondria


What is a glucose 6-phosphate dehydrogenase (G6PD) deficiency?

Most common enzyme deficiency (mutation) world wide
It results in lower NADPH lvls because G6PD catalyes the first committed step of the PPP, this will lead to less glutathione levels
**this effects RBC a lot because they have no other source to make NADPH

This can lead to cell destruction of RBCs triggered by elevated H2O2 during infection, stress or food and may different types of drugs


Who is most effected by G6DP deficiency?

Africans, Asians, Mediterranean or middle eastern decent

**400 million people worldwide