BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 12. CARBOHYDRATE METABOLISM

12.1. Catabolic pathways of carbohydrates

12.1.1. Carbohydrate digestion

The vast majority of CARBOHYDRATES entering The Human Body consist of Polysaccharides—starch and Glycogen—which, along with dietary Oligosaccharides such as sucrose and lactose, are broken down by amylolytic Enzymes of the gastrointestinal tract. Enzymatic Hydrolysis of glycosidic bonds yields Monosaccharides that are absorbed by enterocytes and transported via the bloodstream to other Cells and Tissues for further Processing.

The breakdown of Homopolysaccharides like starch and glycogen begins in the Oral Cavity through the action of α-amylase and α-glucosidase, which are synthesized by the Salivary Glands and are components of saliva.

Mammalian salivary α-amylase is a highly active endohydrolase that catalyzes the hydrolysis of internal α-1,4-glycosidic bonds in amylose, amylopectin, and glycogen molecules:

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The products of polysaccharide hydrolysis by α-amylase are typically dextrins of varying molecular weight, small amounts of maltose and maltotriose, as well as glucose formed via the breakdown of maltose by salivary α-glucosidase (maltase):

It should be noted that α-amylase is highly active only toward heat-treated starch, exhibiting low activity toward "raw" substrates. Having an optimal pH of 6.8–7.2, it loses activity in the acidic environment of The Stomach, which lacks its own amylolytic enzymes. Therefore, carbohydrate Digestion takes place primarily in the Small Intestine with the participation of pancreatic amylolytic enzymes and epithelial Cells of the mucosal lining.

Pancreatic enzymes—such as α-amylase (which, unlike salivary amylase, is equally active toward heat-treated and unheated substrates) and α-dextrinase (oligo-1,6-glucosidase, which hydrolyzes α-1,6-glycosidic bonds at the branch points of amylopectin and glycogen)—sequentially cleave starch and glycogen polymer chains into the Disaccharides maltose and isomaltose. Despite the presence of maltase activity in pancreatic juice, the bulk of disaccharides are hydrolyzed by disaccharidases synthesized by the brush border epithelium of the small intestinal mucosa. Maltase (α-glucosidase), sucrase (β-fructofuranosidase), and lactase (β-galactosidase), which are bound to the external luminal surface of epithelial membranes, complete the enzymatic Digestion of dietary carbohydrates by breaking down maltose, isomaltose, sucrose, and lactose into glucose, galactose, and fructose molecules.

Monosaccharides—the End products of carbohydrate digestion, as well as Cleavage products of Glycoproteins, Glycolipids, and Nucleic Acids—are readily absorbed by the cells of the small intestinal mucosa via Facilitated Diffusion. Driven by a concentration gradient, they are transported from the intestine across the enterocyte membrane at varying rates. The transport rate is highest for galactose, slightly lower for glucose, roughly half as fast for fructose, and even lower for mannose, xylose, and arabinose.

Unlike other monoses, glucose and galactose are also absorbed via Active Transport. Utilizing specific carrier Proteins of this transport system, hexoses are transported across The Cell membrane alongside Na⁺ ions, which enter the cell driven by an electrochemical gradient. In this process, Na⁺ ions "pull" monosaccharides along with them, even against a concentration gradient—that is, when the intracellular glucose concentration exceeds that in the intestinal lumen. The concentration gradient of Na⁺, in turn, is established and maintained by the Na⁺, K⁺-ATPase pump, which actively extrudes Na⁺ ions from the cell in exchange for K⁺ ions.

Inside enterocytes, the absorbed monoses are partially tautomerized into glucose, which enters the intercellular space and subsequently the bloodstream via simple diffusion down a concentration gradient. During the absorptive period—following the digestion of dietary carbohydrates—Blood glucose concentration in the portal vein, the primary vascular highway connecting the intestine and the Liver, can reach approximately 12 mmol/L.

Monosaccharides (primarily glucose, along with fructose, mannose, and galactose) enter hepatocytes via simple diffusion (passive transport) because the intracellular glucose concentration during this period is significantly lower than its level in Blood Plasma.

The major portion of glucose entering the liver is retained within it through the phosphorylation of its primary alcohol group:

The product of this virtually irreversible reaction, catalyzed by the liver-specific enzyme glucokinase, is glucose-6-phosphate. Due to The ionization of its phosphate group, it carries a negative charge and is therefore unable to cross membrane structures or exit the cell.

Liver glucokinase, which has a K_m of approximately 10 mmol/L, rapidly phosphorylates the bulk of the glucose delivered to the liver from the portal vein. A smaller fraction of glucose (about 40%) freely exits the liver into the systemic Circulation and is transported via the blood to other tissues, where it is assimilated. The liver is the sole organ that releases glucose into the general bloodstream.

Glucose entering Muscles and other tissues from the blood is phosphorylated by another enzyme—hexokinase. Unlike glucokinase, hexokinase catalyzes the phosphorylation of all hexoses entering the tissue. In various organisms, hexokinase exists as multiple isoforms that catalyze the same reaction but differ in kinetic properties. For instance, Muscle hexokinase differs from liver glucokinase by its broad substrate Specificity, lower K_m value (0.1 mmol/L), and susceptibility to feedback regulation by the reaction product, glucose-6-phosphate, which acts as an allosteric inhibitor.

An elevated Blood Glucose Level (hyperglycemia) in the systemic circulation during the absorptive period, known as "alimentary hyperglycemia," is a normal physiological state in which blood glucose relatively quickly (within 1.5–2 hours) returns to the normal concentration range of 3.33–5.55 mmol/L (or 60–100 mg/100 mL). Persistent and prolonged hyperglycemia can occur in various pathological conditions involving The Nervous system, Pancreas, other Endocrine glands, and the liver. Both temporary and sustained hyperglycemia (exceeding 10 mmol/L) are typically accompanied by glucosuria—the appearance of glucose in the urine due to the renal threshold being exceeded, rendering the reabsorptive capacity of the renal tubules insufficient.

A drop in blood glucose levels below 3.33 mmol/L constitutes hypoglycemia. Its symptoms include headaches, dizziness, convulsions, and other Central Nervous System dysfunctions, culminating in hypoglycemic coma as the most severe stage. A sharp and substantial drop in blood glucose below a certain critical threshold can cause irreversible and fatal Brain damage, given that Glucose serves as the brain's primary energy source.