Case study on Obesity: A 19-year-old female college student sought medical help because she was 30 kg overweight. Most of her excess weight was in the form of adipose tissue. A medical history revealed that her diet was extremely poor. She consumed virtually no vegetables, whole grains or legumes. Much of her caloric intake was comprised of simple carbohydrates - crackers, white rice, white bread, pastries, desserts, soft drinks, and beer. However, her dietary fat intake was actually quite moderate.

 

1. How might the carbohydrate ingested by this patient supply the NADPH needed for fatty acid biosynthesis?

 

Actually, what makes a person fat, is due to the high levels of carbohydrates that they ingest in their diet and the reason is that when we ingest large amounts of carbohydrates in the diet, they will be converted to fats.

The catabolism of carbohydrates all coincide in the process of glycolysis that produces two pyruvate molecules and ATP intermediaries. Let's see the general mechanism of it:

After this, pyruvate molecules will produce acetyl CoA and then acetyl CoA molecules will enter the Krebs cycle.

The Krebs cycle starts with the production of citrate from acetyl CoA, oxaloacetate and water; then this citrate will be converted to isocitrate, then isocitrate is converted to to alpha-ketoglutarate by means of the enzyme isocitrate dehydrogenase , etc.

When the cells get ENOUGH ATP, they will block all the pathways that produced ATP because they don't want more ATP to be produced and one way to block those processes is by blocking the isocitrate dehydrogenase enzyme so, alpha-ketoglutarate won't be produced and Krebs cycle will be inhibited. Also, citrate will accumulate in the mitochondria and as it cannot convert back to acetyl CoA, then citrate will get out from the mitochondria and get to the cytoplasm where it will dissociate into oxaloacetate and acetyl CoA.:

1. The acetyl CoA in the cytoplasm will convert into malonyl CoA and both will be used to produce fatty acids.
2. The oxaloacetate in the cytoplasm will be used to produce malate and this malate will be converted to pyruvate through the malic enzyme and this reaction produces 1 NADPH.

This is the first source of NADPH. The second source of it is from the HMP shunt. Some glucose molecules instead of developing glycolysis, they convert to glucose-6-phosphate and follow the pathway of the HMP shunt where there is production of Ribose-5-phosphate and NADPH.

So, we have two sources of NADPH. And now, why is NADPH important for fatty acid synthesis? The answer is because the acetyl CoA and malonyl CoA will produce a fatty acid chain by means of an enzyme called Fatty acid synthase that REQUIRES NADPH. So, once we have acetyl CoA, malonyl CoA and NADPH, the enzyme fatty acid synthase will start building fatty acids that later will be stored as fats in adipocytes and the person will increase weight. So, everything started from the metabolism of carbohydrates.

Let's make a final graphic of how carbohydrate metabolism produces NADPH:

Please see the attached file for the complete solution