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. -Extended periods of physical exertion in patients with ME result in the conversion of glycine and cysteine to which of the following compounds?

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11ecba2d_0e31_284d_a3bf_49bf079c203b_MD0008_00 Amino acids are classified as glucogenic or ketogenic depending on the metabolic intermediate to which they are converted. Glucogenic amino acids are converted to pyruvate or citric acid cycle intermediates, which can be converted to glucose. Ketogenic amino acids are converted directly to acetyl-CoA, which can enter the citric acid cycle or be used to form ketone bodies. The passage uses this classification to place amino acids into the three categories in Table 1. Amino acids in Category I are converted exclusively to pyruvate, and those in Category II become acetyl-CoA. Category III consists of amino acids used to make various citric acid cycle intermediates. Glycine and cysteine are Category I amino acids, which are converted directly into pyruvate. Patients with ME at rest have sufficient ATP to convert pyruvate into citric acid cycle intermediates (via oxaloacetate) during aerobic respiration. However, the shortage of oxygen caused by prolonged physical exertion inhibits aerobic respiration by preventing NAD⁺ and FAD, which are used by the citric acid cycle, from being regenerated. To maintain ATP production, cells switch from aerobic to anaerobic respiration, which does not require oxygen and consists of glycolysis and fermentation. Glycolysis contributes two molecules of ATP by breaking down glucose into two molecules of pyruvate. During fermentation, the NAD⁺ required for glycolysis is generated by reducing pyruvate to lactate with the enzyme lactate dehydrogenase. Therefore, glycine and cysteine are ultimately converted to lactate during periods of physical exertion. (Choices A and D) Patients with ME cannot convert pyruvate into acetyl-CoA, which is a precursor molecule for the citric acid cycle intermediates such as fumarate and isocitrate. (Choice C) Conversion of pyruvate to glucose occurs in gluconeogenesis, which requires ATP. Aerobic respiration is required to produce sufficient ATP for gluconeogenesis. Educational objective: Glucogenic amino acids are converted to pyruvate, which can be used to make glucose or citric acid cycle intermediates. Ketogenic amino acids are converted directly to acetyl-CoA, which can enter the citric acid cycle or be used to form ketone bodies. In the absence of oxygen, pyruvate is reduced to lactate to regenerate NAD⁺ during fermentation.

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