The glycolytic pathway enables the conversion of glucose-6-phosphate (G6P) to pyruvate, resulting in the production of a small amount of ATP. This process does not require mitochondria or oxygen. In the absence of mitochondria, cells ferment pyruvate into lactate, which is then excreted as waste. However, most cells import pyruvate into mitochondria where it is converted to acetyl CoA by pyruvate dehydrogenase. Acetyl CoA combines with oxaloacetate to form citrate, which then goes through the tricarboxylic acid (TCA) cycle, eventually regenerating oxaloacetate. As pyruvate is metabolized through the TCA cycle, carbon dioxide (CO2) is released as waste. This process also generates guanosine triphosphate (GTP), flavin adenine dinucleotide hydride (FADH2), and nicotine adenine dinucleotide hydride (NADH). FADH2 and NADH are utilized by the electron transport system and oxidative phosphorylation to produce a relatively large amount of ATP. It is important to note that this ATP generation process is entirely dependent on the presence of oxygen. Certain cells, such as erythrocytes and lens cells of the eye, lack or have very few mitochondria and therefore rely solely on glucose for energy. The brain, under normal conditions, exclusively utilizes glucose as a fuel source. It has minimal capability to oxidize free fatty acids (FFAs) and only marginal capacity to utilize lactate, ketone bodies (KBs), and amino acids (AAs) for energy. Consequently, it is crucial to maintain blood glucose levels above a certain minimum threshold to prevent central nervous system (CNS)-related symptoms. The initial symptoms resulting from hypoglycemia include nausea, sweating, and cardiac arrhythmias, whereas a further decrease in blood glucose can lead to neuroglycopenia-induced cognitive dysfunction, loss of motor coordination, and potentially even coma.
metabolize G6P to pyruvate via the glycolytic pathway, which yields a small amount of ATP without requiring mitochondria or O2. Cells without mitochondria ferment pyruvate to lactate and export lactate as waste. Most cells import pyruvate into mitochondria, convert it to acetyl CoA by pyruvate dehydrogenase, and then condense acetyl CoA with oxaloacetate to form citrate. Citrate is cycled through the tricarboxylic acid (TCA) cycle back to oxaloacetate. This metabolism of pyruvate through the TCA cycle releases CO2 as waste and generates guanosine triphosphate (GTP) along with flavin adenine dinucleotide hydride (FADH2) and nicotine adenine dinucleotide hydride (NADH). FADH2 and NADH are used by the electron transport system and oxidative phosphorylation to ultimately generate relatively large amounts of ATP through a process that is absolutely dependent on O2. Cells with no or very few mitochondria (e.g., erythrocytes, lens cells of the eye) are absolutely dependent on glucose for energy. Additionally the brain can only use glucose under normal conditions, in that it has essentially no capacity for oxidation of FFAs and only marginal capacity for the use of lactate, ketone bodies (KBs), and AAs as fuels. Thus in all metabolic phases, maintenance of blood glucose above a certain minimal threshold is absolutely necessary to avoid central nervous system (CNS)-related symptoms, beginning with those caused by a hypoglycemia-activated autonomic response (e.g., nausea, sweating, cardiac arrhythmias). If blood glucose continues to fall, progression to symptoms caused by neuroglycopenia (e.g., cognitive dysfunction, loss of coordinated motor function, and ultimately even coma