Fauvism

Does fatty acid synthesis require a large amount of NADPH? Is the NADPH that is derived from converting oxaloacetate to malate enough?

Yes it does and no it is not enough

How much NADPH is required to synthesize C16:0?

14 NADPH

What is an alternative pathway than converting oxaloacetate to malate to produce NADPH?

Pentose phosphate pathway (P₃)

What are the two phases of the pentose phosphate pathway?

1. Oxidative phase

2. Non-oxidative phase

What does the oxidative phase produce?

1. Produces NADPH to support anabolic processes such as fat synthesis

2. Produces ribose-5-phosphate for nucleotide synthesis

What purpose does the non-oxidative phase serve?

Its purpose is for the interconversion of C3, C4, C5, C6, and C7 monosaccharides. It is challenging to digest longer chain carbons and therefore converting them into carbohydrates we can use.

Describe the steps for oxidative phase

1. Glucose is converted to glucose-6-phosphate by hexokinase

2. Glucose-6-phosphate is oxidized to 6-phosphoglucono-delta-lactone by glucose-6-phosphate dehydrogenase and NADP+ is reduced to NADPH

3. 6-phosphoglucono-delta-lactone is converted to 6-phosphogluconate by lactonase and a water molecule is consumed

4. 6-phospho-gluconate is oxidized to ribulose-5-phosphate by 6-phosphogluconate dehydrogenase and NADP⁺ is reduced to NADPH and CO₂ is produced

What is the chemical reaction for the oxidative phase?

Glu-6-P + 2 NADP⁺ + H₂O —> ribulose-5-P + 2NADPH + 2H⁺ + CO₂

How are the pentose phosphate pathway and glycolysis linked?

They are linked by transketolase and transaldolase

What happens in the non-oxidative phase?

1. Ribulose-5-P is isomerize to ribose-5-phosphate (5C) and xylulose-5-phosphate (5C)

2. Transketolase can convert ribose-5-P and xylulose-5-P into GAP (3C) and sedoheptulose-7-P (7C)

3. Transaldolase can convert GAP and sedoheptulose-7-P into fructose-6-P (6C) and erythrose-4-P (4C)

4. Transketolase can convert erythrose-4-P and xyulose-5-P into fructose-6-P and GAP which serve as intermediates in glycolysis

Is there any loss of carbon in non-oxidative phase of pentose phosphate pathway?

No

What is fauvism caused by? What is fauvism?

Glucose-6-phosphate dehydrogenase deficiency (this is the first enzyme in PPP). It is hemolytic anemia.

What do fava beans contain high concentrations of? What are they?

Vicine and convicine which are glycosides.

What can vicine and convicine be converted to? What do these products do?

Vicine is converted to divicine and convicine is converted to isouramil. Isouramil and divicine are responsible for oxidative stress as they produce reactive oxygen species.

What happens in a red blood cell with normal glucose-6-phosphate dehydrogenase when fava beans are consumed?

1. The pentose phosphate pathway is carried out effectively and ribulose-5-phosphate is produced along with NADPH.

2. Since NADPH is available glutathione reductase can work normally to produce glutathione from glutathione disulfide.

3. Glutathione is then converted back to glutathione disulfide by glutathione peroxidase which takes reactive oxygen species produced by divicine and isouramil and converts them to water and oxygen

4. Red blood cell is normal and in tact

What happens in red blood cells that are deficient in glucose-6-phosphate dehydrogenase when fava beans are consumed?

1. The pentose phosphate pathway cannot be carried out, therefore, NADPH is not being produced and NADP⁺ is accumulating

2. Glutathionine reductase cannot convert glutathione disulfide into glutathione and therefore the levels decrease

3. Since there are low levels of glutathione the enzyme glutathione peroxidase is not active and the reactive oxygen species will not be converted into water and oxygen

4. This leads to oxidative damage, hemolysis and eventually to acute hemolytic anemia

How many NADPH are being produced in pentose phosphate pathway?

2 NADPH

Where does the pentose phosphate pathway occur?

In the cytoplasm