How do fatty acids help prevent the oxidation of glucose in insulin-sensitive cells?

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Question restatement: How do fatty acids help prevent the oxidation of glucose in insulin-sensitive cells?

Option 1: Fatty acids cause the endocytosis of GLUT-4 transporters so that there are less of them on the plasma membrane. This would reduce glucose uptake, but the mechanism described here does not involve the oxidation of fatty acids inhibiting a glucose-oxidation enzyme. It focuses on transporter trafficking rather than the intracellular metabolic fate of glucose, so this option misaddresses the specific interaction between fatty acid oxidation and glucose oxidation.

Option 2: The oxidation of fatty acids inhibits the pyruvate dehydrogenase complex. This is a direct link to glucose oxidation: PDH converts pyruvate to acetyl-CoA for entry into the citric acid cycle. When fatty acid oxidation is active, high levels of NADH and acetyl-CoA promote PDH inhibition (via PDH kinase), reducing pyruvate oxidation and thereby limiting glucose oxidation. This reflects the metabolic cross-talk described in the Randle cycle, where fatty acid oxidation suppresses carbohydrate oxidation in insulin-sensitive tissues.

Option 3: Fatty acids compete with glucose for GLUT-4 transporters. GLUT-4 mediates glucose entry into adipose and muscle cells, but fatty acids do not compete for GLUT-4 transporters. Fatty acids are not transported by GLUT-4, so this option misstates transporter specificity and fails to explain a metabolic interaction that would inhibit glucose oxidation.

Option 4: High levels of fatty acids stop the secretion of insulin from pancreatic beta-cells. Insulin secretion is a pancreatic process, not a mechanism by which fatty acid oxidation directly reduces glucose oxidation inside insulin-sensitive cells. This statement describes an endocrine effect outside the intracellular PDH regulation pathway, making it inappropriate for explaining the inhibition of glucose oxidation in peripheral tissues.

Putting these together, the most coherent mechanism that ties fatty acid oxidation to reduced glucose oxidation in insulin-sensitive cells is the inhibition of pyruvate dehydrogenase by fatty-acid-derived metabolic signals, which reduces flux from glycolysis-derived pyruvate into the TCA cycle. The other options either describe transporter or insulin-secretion effects that do not align with the core metabolic interaction, or mischaracterize the transporter involvement of fatty acids.

2025_S1C_BCMB2001/BCMB2901/MEDS2003 Metabolism Revision 2 - Lectures 5/6/7/8/9

How do fatty acids help prevent the oxidation of glucose in insulin-sensitive cells?

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