Figure 2.

(A) Glycolysis: This includes 10 consecutive enzymatic reactions in the conversion of glucose into two molecules of pyruvate, which connect with other metabolic pathways. Glucose is phosphorylated to glucose 6-phosphate by the enzyme hexokinase (HK). Glucose 6-phosphate is turned into fructose 6-phosphate by glucose phosphate isomerase (GPI). Phosphofructokinase-1 (PFK) catalyzes the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP. 6-phosphofructo2-kinase/fructose 2,6-bisphosphatase (PFKFB), a family of bifunctional enzymes that control the levels of fructose 2,6-bisphosphate (PFKFB3 and PFKFB4 are the two main isoenzymes of this family) (PFK and PFKFB are the two major regulatory enzymes in glycolysis). Subsequently, the aldolase enzyme catalyzes a reversible reaction in which fructose 1,6-bisphosphate converts into glyceraldehyde-3-phosphate (GLAP) and dihydroxyacetone phosphate (DHAP). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) produces 1,3-bisphosphoglycerate. Next, phosphoglycerate kinase (PGK) forms ATP and 3-phosphoglycerate. Phosphoglycerate mutase (PGM) isomerizes 3-phosphoglycerate into 2-phosphoglycerate. Next, enolase converts 2-phosphoglycerate to phosphoenolpyruvate, which is phosphorylated to form a molecule of pyruvate and a molecule of ATP via pyruvate kinase (PK). Finally, lactate dehydrogenase (LDH) catalyzes the conversion of pyruvate to lactate. (B) Krebs cycle: The TCA cycle starts with the combination of acetyl-CoA, generated from fatty acids, amino acids, or pyruvate oxidation, with oxaloacetate (OAA) to produce citrate. Citrate is converted into isocitrate. The cycle continues with two consecutive oxidative decarboxylations in which isocitrate is converted into the α-ketoglutarate (α-KG) and the succinyl-CoA concomitantly, producing two CO₂ and two NADH. Succinyl-CoA coverts into succinate, coupled with the release of ATP. Subsequently, fumarate is formed by the oxidation of succinate. During this step, two hydrogen atoms are transferred to FAD, producing 2FADH. Next, fumarate is converted into malate and further into OAA, which combines with another acetyl-CoA, continuing the cycle [51]. (C) De novo lipogenesis C: In this simplified scheme, pyruvate from glycolysis feeds acetyl-CoA to the TCA cycle. Citrate from the TCA cycle is converted to acetyl-CoA in the cytosol by ATP citrate lyase (ACLY). Acetyl-CoA from the TCA cycle and other sources is subsequently converted to complicated fatty acids by a series of enzymes including ATP-citrate lyase (ACLY), acetyl-CoA carboxylases 1 (ACC1), fatty acid synthase (FASN), and stearoyl-CoA desaturase-1 (SCD1). (D) Fatty acid β-oxidation: Each cycle leads to the formation of acetyl-CoA, nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FADH 2). The electron carriers NADH and FADH2 are used by the mitochondrial respiratory chain to generate ATP. (E) Triacylglycerol synthesis: This reaction occurs at the surface of the endoplasmic reticulum (ER) bilayer membrane. The first step in this pathway is the acylation of glycerol-3-phosphate by glycerol-3-phosphate acyltransferase (GPAT), producing lysophosphatidic acid. This is followed by further acylation by LPA acyltransferase (LPAAT) and dephosphorylation by phosphatidic acid phosphorylase (PAP) to yield diacylglycerol (DAG). The final step is converting 1,2-diacylglycerol into triacylglycerol (TAG), which is catalyzed by diacylglycerol acyltransferase (DGAT).