Understanding Carbohydrate Metabolism and Glycolysis
4. Metabolism of Carbohydrates: Glycolysis: All carbohydrates obtained from the diet are digested by pancreatic and salivary enzymes, absorbed by the intestine, and metabolized in the blood and liver. Glucose is distributed throughout the body.
Glycolysis: Transformation of pyruvic acid (pyruvate) from glucose. The net reaction is: Glucose + 2NAD+ + 2ADP → 2 Pyruvates + 2NADH + 2ATP. It’s a highly energetic pathway, although it is fundamental (common to all eukaryotic and prokaryotic cells). It is anaerobic, meaning it does not require O2 to occur. All reactions except three are reversible: the conversion of glucose to glucose 6-P, the step from fructose 6-P to fructose 1,6-diphosphate, and the conversion of phosphoenolpyruvate to pyruvate. These steps are catalyzed by kinases and involve 3 ATP. Glycolysis interconnects with other metabolic pathways, all ending in monosaccharides that are components of glycolysis, synthesis, and the metabolism of fatty acids. Within the pathways, there is a variation: the step between 1,3-diphosphoglycerate to 3-phosphoglycerate has an intermediary step (2,3-diphosphoglycerate), which transports O2 via hemoglobin.
5. Reactions Involving Pyruvate: 1. CoA-Pyruvate DH – (NAD+ → NADH) → Acetyl CoA + CO2. This reaction is irreversible, aerobic (requires the presence of O2), and mitochondrial, considered the first reaction of the Krebs cycle. 2. L-Lactate-Pyruvate DH – (NADH → NAD+) → Lactate (lactic fermentation). This prevents anaerobic reactions from blocking conditions in anaerobic glycolysis. 3. Pyruvate – (releases CO2) – pyruvate decarboxylase → Acetaldehyde – Alcohol DH – (NADH → NAD+) → ethanol (alcoholic fermentation).
6. Elimination and Storage of NH3: Urea Cycle: Ammonia is toxic. It combines with bicarbonate to form carbamyl phosphate (through the enzyme carbamyl phosphate synthetase with the intervention of 2 ATP molecules). This carbamyl phosphate binds to citrulline (by ornithine carbamoyl transferase) inside the mitochondria and leaves the cytoplasm. There, it combines with aspartic acid using 2 ATP to form succinic acid. This is converted into arginine, which is then split into fumaric acid and ornithine (which again enters the mitochondria) and urea.
Urea is easily excreted (in urine) and is not toxic. It is involved in high protein metabolism, dehydration processes, and renal failure, diagnosed alongside creatinine levels. When NH3 levels are elevated, it is also removed through the following reactions: α-Ketoglutaric acid + NH3 – Glutamic DH – (NADH → NAD+) → Glutamic acid + NH3 – Glutamine synthetase – (ATP → ADP) → Glutamine → α-Ketoglutaric acid. Glutamic synthetase → Glutamic acid + NH3. * NH3 – (urea cycle) → urea. When NH3 levels drop, the reaction shifts in the opposite direction to remove urea.
7. Krebs Cycle (of citric acid) consists of cyclic reactions catalyzed by a set of enzymes in the mitochondria, whose main mission is to extract energy from the metabolism of carbohydrates, lipids, and proteins into two compounds to convert them into reduced forms (NADH and FADH2), with the removal of CO2, which then enters the respiratory chain where the final electron acceptor is O2, coupled with oxidative phosphorylation to obtain ATP. Other functions include metabolic pathways; sources of precursors for metabolic synthesis of glucose, amino acids, nitrogenous bases, and porphyrins.
Energy balance for one complete turn: 3 NADH; 1 FADH2; 2 CO2; 1 GTP.
8. Different Reactions in Gluconeogenesis: Citing Glycolysis and Gluconeogenesis Substrates: The reactions are similar to glycolysis, except for the 3 irreversible steps. Pyruvate – (ATP → ADP) – pyruvate carboxylase – (adds CO2) → Oxaloacetic acid – (NADH → NAD+) – malate DH → Malic acid – MDH (NAD+ → NADH) → Oxaloacetic acid – (releases CO2) – phosphoenolpyruvate carboxykinase – (GTP → GDP) → Phosphoenolpyruvate.
The 3 irreversible steps are the conversion of glucose-6-P, the step from fructose-6-P to fructose-1,6-diphosphate, and pyruvate to phosphoenolpyruvate. The substrates for gluconeogenesis include pyruvic acid, muscular lactate (Cori cycle), lipid metabolism (fatty acids and glycerol → Acetyl CoA), and gluconeogenic amino acids, which can be used for glucose synthesis, interacting with the Krebs cycle (alanine and glutamine).
9. Cori Cycle: