Textbook - BIOLOGICAL CHEMISTRY - Gubsky Yu.I. - 2000

Section III. METABOLISM OF THE MAIN CLASSES OF BIOMOLECULES

CHAPTER 12. CARBOHYDRATE METABOLISM. II. ALTERNATIVE PATHWAYS OF MONOSACCHARIDE METABOLISM. REGULATION OF GLUCOSE METABOLISM

12.2. METABOLISM OF FRUCTOSE AND GALACTOSE

Important substrates of METABOLISM/26.html">Energy Metabolism are the Monosaccharides D-fructose and D-galactose, which enter The Human Body primarily through dietary Disaccharides of PLANT AND ANIMAL origin: fructose as part of sucrose, which is hydrolyzed in the intestine by the enzyme sucrase into glucose and fructose, and galactose as part of the "milk sugar" lactose, which is cleaved by intestinal lactase (β-galactosidase) into galactose and glucose.

Upon crossing the Plasma Membranes into the Cells, Fructose and Galactose enter metabolic pathways by being converted into phosphorylated glucose esters or glycolytic intermediates.

Class="center">Metabolism of Fructose

The incorporation of fructose into glucose metabolism is carried out by the action of the following Enzymes:

a) non-specific hexokinase, which catalyzes the phosphorylation of various hexoses:

The reaction product, D-fructose-6-phosphate, is a metabolite of the glycolytic oxidation of glucose. This pathway of Fructose Metabolism operates in the cells of many Organs, particularly in Muscles and Kidneys;

b) specific fruktokinase, which catalyzes the phosphorylation of fructose not at the 6th, but at the 1st carbon atom:

The fructokinase pathway of fructose metabolism Functions in the Liver. The reaction product, D-fructose-1-phosphate, is cleaved by aldolase (fructose-1-phosphate aldolase) into two trioses:

The resulting dihydroxyacetone phosphate is a glycolytic intermediate that is converted into glyceraldehyde-3-phosphate by the action of Triosephosphate isomerase. The second product of the aldolase reaction, glyceraldehyde, is also phosphorylated to yield glyceraldehyde-3-phosphate (catalyzed by triosekinase):

Thus, the fructokinase pathway of fructose metabolism intersects with Glycolysis at the stage of formation of two phosphotriose molecules—glyceraldehyde-3-phosphate.

Features of Fructose Metabolism in the Human Body

The main source of fructose in the human body is dietary intake, although a certain amount of this hexose is synthesized from glucose in specialized Tissues.

The synthesis of endogenous fructose proceeds via The conversion of glucose into the hexahydric alcohol sorbitol According to the following scheme:

1. In the human body, fructose is synthesized from glucose in the Seminal Vesicles; the concentration of fructose in seminal fluid reaches 10 mM. Due to the ability of sperm Cell/35.html">Mitochondria to oxidize fructose via fructolysis, it serves as an energy source for sperm motility.

2. Fructose is present in certain concentrations in the eye lens, where it is also produced from glucose via sorbitol. The activity of this metabolic pathway increases in Diabetes Mellitus; because sorbitol crosses cell membranes with difficulty, it accumulates along with fructose in the lens, which constitutes the biochemical basis for The Development of diabetic cataract.

3. There are hereditary enzymopathies associated with Genetic Defects in the synthesis of enzymes involved in fructose metabolism:

a) fructose intolerance is a genetic disorder whose molecular basis is a congenital deficiency of fructose-1-phosphate aldolase, which leads to the accumulation of fructose-1-phosphate in tissues; this compound acts as an inhibitor of certain Carbohydrate Metabolism enzymes, notably Glycogen phosphorylase. The condition manifests as fructosemia, fructosuria, and severe hypoglycemia that develop after consuming a fructose-containing diet;

б) fructosemia — fructose metabolism disorder caused by fructokinase deficiency. This enzymopathy is characterized by impaired cellular utilization of fructose without significant clinical manifestations.

Galactose Transformation

The incorporation of galactose into metabolic pathways follows this mechanism:

(1) phosphorylation of D-galactose at the 1st carbon atom (catalyzed by galactokinase):

(2) conversion of D-galactose-1-phosphate into the epimeric molecule D-glucose-1-phosphate. The reaction involves the coenzyme nucleotide UDP (uridine diphosphate), which functions as a carrier of hexose groups in the form of the nucleotide sugar UDP-1-hexose:

The reaction is catalyzed by galactose-1-phosphate uridylyltransferase (UDP-glucose: D-galactose-1-phosphate uridylyltransferase).

The regeneration of UDP-1-glucose—that is, the Conversion of the galactose radical into a glucose radical (and the reverse epimeric process)—occurs within the UDP-hexose nucleotide sugar molecule under the action of the NAD-dependent enzyme UDP-galactose 4-epimerase.

(3) Glucose-1-phosphate, the product of reaction (2), is converted into glucose-6-phosphate by the action of phosphoglucomutase.

The sequence of reactions for incorporating galactose into glucose metabolism is shown in Fig. 12.4:

Fig. 12.4. Scheme of galactose incorporation into glucose metabolism. E₁ — galactokinase; E₂ — galactosyl-1-phosphate uridylyltransferase; E₃ — UDP-galactose 4-epimerase; E₄ — phosphoglucomutase.

The described sequence of reactions converting galactose to glucose is also utilized for the reverse process—the synthesis of galactose in the Mammary Glands, where the monosaccharide is used to produce the milk sugar lactose.

Galactosemia

A hereditary defect in the synthesis of galactose-1-phosphate uridylyltransferase manifests as a congenital enzymopathy known as galactosemia. Due to the inability of the body's biochemical systems to convert galactose into glucose, galactose and galactose-1-phosphate accumulate in the Blood and Internal Organs of patients, resulting in hepatomegaly, cataract formation, and mental retardation. The condition appears in early infancy upon milk consumption, and its progression can be prevented through appropriate dietary restrictions.