NADPH required for fatty acid synthesis can come from?

SJH Nursing Officer - 2019

Biochemistry & Nutrition

Easy

Appeared in: SJH Nursing Officer - 2019

Explanation

Fatty acid synthesis is an anabolic, reductive process occurring in the cytosol that requires the reducing agent NADPH.
The Hexose Monophosphate (HMP) Shunt, also known as the Pentose Phosphate Pathway, is the principal source of NADPH for this process.
The oxidative decarboxylation of malate by malic enzyme is another significant source of cytosolic NADPH.
The oxidation of isocitrate in the cytosol by NADP+-dependent isocitrate dehydrogenase also contributes to the NADPH pool.
Since all three listed pathways are valid sources of cytosolic NADPH for lipogenesis, the most comprehensive answer is 'All of these'.

Option A: This option is incomplete. While the Hexose Monophosphate (HMP) shunt is the major source of NADPH, it is not the only source available for fatty acid synthesis.
Option B: This option is incomplete. The oxidative decarboxylation of malate is a valid source of NADPH, but it is not the only one. The HMP shunt is a more significant contributor.
Option C: This option is incomplete. While the extra-mitochondrial oxidation of isocitrate does produce NADPH, it is considered a minor source compared to the HMP shunt and malic enzyme.

Clinical Relevance

Nursing practice connection: This is primarily an exam-oriented knowledge point with limited direct bedside application, so retain Biochemical sources of NADPH for fatty acid synthesis as background academic context rather than a clinical decision trigger.
In tissues with high rates of fatty acid synthesis (e.g., liver, adipose tissue, lactating mammary glands), the activity of these NADPH-producing pathways is upregulated.
A high-carbohydrate diet stimulates insulin release, which promotes fatty acid synthesis and thus increases the demand for NADPH, enhancing flux through these pathways.
What if? If a patient has a Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, the HMP shunt is impaired. This reduces NADPH production, which not only affects fatty acid synthesis but more critically, it impairs the ability of red blood cells to protect against oxidative damage, leading to hemolytic anemia.

How to Approach the Question

First, identify the core of the question: it asks for the sources of NADPH, the specific reducing agent needed for fatty acid synthesis.
Recall the major metabolic pathways that occur in the cytosol and produce NADPH. The most prominent is the Hexose Monophosphate (HMP) Shunt or Pentose Phosphate Pathway.
Evaluate each option individually. You should recognize the HMP shunt (Option A) as a correct source.
Consider the other options. The conversion of malate to pyruvate (Option B) and isocitrate to α-ketoglutarate (Option C) are also known cytosolic reactions that can produce NADPH.
When you identify that multiple options (A, B, and C) are factually correct, and an 'All of these' option is available, it is the most complete and therefore the best answer.

Concept Tested & Keywords

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E6 Textbook of Biochemistry for medical StudentsDM Vasudevan Part 1 (pp 26-370 of 370) p. 340-342

E6 Harper's Illustrated Biochemistry2023 (pp 26-793 of 813) p. 119-121

E6 textbook of Applied Biochemistry and Nutrition & DieteticsHarbans Lal (pp 26-464 of 479) p. 76-78