Passage Myalgic encephalopathy (ME), or chronic fatigue syndrome (CFS), is a physiological disease that affects 0.15% of the human population. Compared with healthy individuals, persons with ME experience reduced phospholipid levels, muscular degeneration, urinary urgency, and other symptoms that contribute to a lower quality of life. Studies in resting subjects have yielded inconsistent data and failed to identify a unique metabolic defect in patients with ME.Analyzing the blood plasma of male and female patients with ME, physicians have observed that male patients display elevated levels of 3-methylhistidine, a marker of protein catabolism. Researchers expanded this finding by measuring the serum concentration of amino acids in blood samples obtained from nonfasting ME patients and healthy controls. Amino acids were classified into separate categories according to their metabolic intermediates.Table 1 Classification of Amino Acids in Blood Plasma Figure 1 Serum concentrations of amino acids in patients with ME and healthy controls (HC)Next, researchers hypothesized that the inhibition of pyruvate dehydrogenase (PDH) and impairment of fatty acid oxidation were responsible for the fluctuations in amino acid levels. PDH function and lipid metabolism were studied in peripheral blood mononuclear cells (PBMCs) by measuring the gene expression of proteins within regulatory pathways. Researchers monitored the mRNA levels of the inhibitor pyruvate dehydrogenase kinase 1 (PDK1) and of sirtuin 4 (SIRT4), which removes lipoic acid groups from the PDH complex. They also examined lipid metabolism by measuring the mRNA levels of peroxisome proliferator-activated receptor-α (PPARα), a transcription factor that upregulates the uptake of fatty acids. The mRNA level of each protein in PBMCs of patients with ME was evaluated against healthy controls, as shown in Figure 2. Figure 2 Gene expression of PDK1, SIRT4, and PPARα in PBMCs Adapted from Fluge Ø, Mella O, Bruland O, et al.. JCI Insight. 2016;1(21):e89376. -If lower phospholipid levels in ME patients are due to inhibition of fatty acid synthesis, researchers would most likely observe which of the following?

Question

Quizplus · Accepted Answer

11ecba2d_0e2c_9469_a3bf_ddc39e4ce8f0_MD0008_00 Fatty acid synthesis is an anabolic process that builds lipids in the cytosol. Anabolic processes generally require energy, reducing power, and sufficient precursor molecules: in fatty acid synthesis these requirements are satisfied by ATP, NADPH, and acetyl-CoA, respectively. During fatty acid synthesis, NADPH is oxidized to NADP⁺ to reduce the carbonyl groups and carbon-carbon double bonds on each acetyl-CoA molecule added to the fatty acid chain. If fatty acid synthesis is inhibited in ME patients, the conversion of NADPH to NADP⁺ will occur less frequently, and cytosolic NADPH will build up. (Choice B) Fatty acid synthesis takes place in the cytosol, not the mitochondria. In addition, cytosolic acetyl-CoA levels would most likely increase when fatty acid synthesis is inhibited because less acetyl-CoA is consumed. (Choice C) Fumarate concentration is not directly related to fatty acid synthesis and will most likely be unaffected. (Choice D) Lysine is not directly involved in fatty acid synthesis. In addition, figure 1 shows that category II amino acids, including lysine (K), have decreased levels in ME patients. Educational objective: Acetyl-CoA, NADPH, and ATP are the reactants needed to generate fatty acid chains during lipid synthesis. The pentose phosphate pathway generates the NADPH needed to reduce the carbonyl groups from each molecule of acetyl-CoA that is added to a fatty acid chain.

Passage Myalgic Encephalopathy (ME), or Chronic Fatigue Syndrome (CFS), Is a a Physiological