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As shown in Table 1 , the contribution of each pathway is determined by (1) the fasting stage and its effect on the mitochondrial NADH/NAD + ratio, (2) the gluconeogenesis substrate and the different enzymes it engages to provide the cytoplasmic NADH that GAPDH requires in the later stages of gluconeogenesis, and (3) accumulation of NH 4 + in the hepatocytes that forces the urea cycle.29,31,39 Table 1