Carbohydrate Digestion
The main dietary carbohydrates are starch, sucrose, and lactose. Starch is composed of glucose residues joined by α-1,4-glycosidic and α-1,6-glycosidic bonds.
Starch breakdown begins in the oral cavity under the action of salivary α-amylase, yielding dextrins. The stomach lacks carbohydrate-hydrolysis enzymes, allowing only residual salivary amylase activity. In the duodenum, pancreatic α-amylase digests starch into maltose (α-1,4) and isomaltose (α-1,6).
Membrane-bound glycosidases operate on the brush border of enterocytes: the sucrase-isomaltase complex hydrolyzes maltose, isomaltose, and sucrose; lactase (β-glycosidase) cleaves lactose into galactose and glucose. Lactase activity peaks in infants and declines with age, leading to lactase deficiency in some adults.
Monosaccharide Absorption
- Facilitated diffusion via specific transporters—characteristic of fructose (GLUT5), and also operational for glucose and galactose.
- Secondary active transport via Na⁺ symport (SGLT)—for glucose and galactose against their concentration gradient; the Na⁺ gradient is maintained by the Na⁺/K⁺-ATPase at the expense of ATP.
- Monosaccharide efflux from enterocytes into the bloodstream occurs via facilitated diffusion (GLUT2).
Glucose uptake by tissue cells is mediated by proteins of the GLUT family. Of particular importance is GLUT4, the insulin-dependent transporter in muscle and adipose tissue.
Intracellular Phosphorylation of Glucose
Upon entering the cell, glucose is immediately phosphorylated to glucose-6-phosphate. The reaction is catalyzed by:
- Hexokinase—low Kₘ (~0.1 mmol/L), functions in all tissues, and is inhibited by its product, glucose-6-phosphate.
- Glucokinase—high Kₘ (~10 mmol/L), induced by insulin, functions in hepatocytes and pancreatic β-cells.
Glucose-6-phosphate serves as a central hub metabolite used for the synthesis of glycogen, pentoses, other monosaccharides, and amino acids, as well as for catabolism to CO₂ and H₂O with ATP generation, or to lactate.
Glycogen synthesis
Glycogenesis is active during the absorptive period (1–2 hours postprandial). Stages:
- Glucose → glucose-6-phosphate (hexokinase/glucokinase).
- Glucose-6-phosphate → glucose-1-phosphate (phosphoglucomutase).
- Glucose-1-phosphate + UTP → UDP-glucose + pyrophosphate (UDP-glucose pyrophosphorylase).
- Glycogen synthase transfers a glucose residue from UDP-glucose onto a primer of 5–8 residues, forming an α-1,4-glycosidic bond.
- After chain elongation to ~12 residues, the branching enzyme (amylo-1,4→1,6-glucosidase / branching enzyme) transfers a 5–6 residue fragment to form an α-1,6-bond—the branch point.
Glycogen Mobilization
Glycogenolysis occurs during the postabsorptive period (10–18 hours of fasting) and during intensive physical exertion. The key enzyme is glycogen phosphorylase, which cleaves α-1,4-bonds to yield glucose-1-phosphate. At branch points, when 4 residues remain,
Glucose-1-phosphate is isomerized to glucose-6-phosphate. In muscle, it is used for local energy demands (glycolysis). In the liver, the action of glucose-6-phosphate phosphatase yields free glucose, which enters the bloodstream to maintain glycemia.
Hormonal Regulation
Glycogen synthesis and breakdown are reciprocally regulated via the phosphorylation of two key enzymes: glycogen synthase (active in the dephosphorylated state) and glycogen phosphorylase (active in the phosphorylated state). The metabolic state is assessed by the insulin-glucagon ratio (IGR).
Insulin (high IGR, postprandial state): via its tyrosine kinase receptor, activates protein phosphatase 1 (glycogen-associated), which dephosphorylates both enzymes—glycogen synthase is activated, while glycogen phosphorylase is inactivated. Concurrently, insulin stimulates GLUT4 translocation, induces glucokinase, and activates phosphodiesterase, which degrades cAMP.
Glucagon (in the liver) and adrenaline (via β₂-adrenoceptors) act through G-proteins and adenylyl cyclase: ATP → cAMP → activation of protein kinase A (PKA). PKA phosphorylates phosphorylase kinase, which in turn activates glycogen phosphorylase, while simultaneously phosphorylating and inactivating glycogen synthase. Adrenaline via α₁-receptors triggers the inositol trisphosphate pathway and Ca²⁺-dependent activation of phosphorylase kinase.
Key points
- Starch is hydrolyzed by salivary and pancreatic α-amylases into maltose and isomaltose, and further by brush-border glycosidases into monosaccharides.
- Glucose is absorbed via secondary active transport with Na⁺ (SGLT) and facilitated diffusion; it enters tissues via GLUT transporters, with GLUT4 being insulin-dependent.
- Hexokinase has a low Kₘ and is product-inhibited; glucokinase has a high Kₘ and is induced by insulin.
- Glycogen synthesis proceeds via UDP-glucose; glycogen synthase forms α-1,4-bonds, and the branching enzyme forms α-1,6-bonds.
- Glycogen breakdown is catalyzed by glycogen phosphorylase; branch points are resolved by the debranching enzyme complex (oligo-1,4→1,4-glucantransferase and α-1,6-glucosidase).
- Only the liver contains glucose-6-phosphatase and supplies free glucose to the bloodstream.
- Insulin activates glycogen synthase via dephosphorylation; glucagon and adrenaline via cAMP and PKA promote breakdown and inhibit synthesis.