Biological Chemistry - Berezov, T. T., Korovkin, B. F. 1998

Carbohydrate Metabolism
Pentose Phosphate Pathway of Carbohydrate Oxidation
Regulation of Carbohydrate Metabolism

The regulatory pathways of Carbohydrate METABOLISM are extremely diverse. At all Levels of biological Organization, carbohydrate metabolism is regulated by factors that influence The activity of Enzymes involved in carbohydrate-related reactions. These factors include Substrate Concentration, the levels of products (metabolites) from specific reactions, oxygen availability, Temperature, biological membrane permeability, the concentration of Coenzymes required for particular reactions, and others (see Chapter 4).

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Fig. 10.13. Modern scheme of the Pentose Phosphate Pathway of carbohydrate oxidation, illustrating its relationship with Glycolysis (after Hers).

1 - transketolase; 2 - transaldolase; 3 - aldolase; 4 - Phosphofructokinase; 5 - fructose-1,6-bisphosphatase; 6 - hexokinase; 7 - glucosephosphate isomerase; 8 - Triosephosphate isomerase; 9 - glucose-6-phosphate dehydrogenase; 10 - 6-phosphogluconolactonase; 11 - 6-phosphogluconate dehydrogenase; 12 - isomerase; 13 - epimerase; 14 - Lactate dehydrogenase.

This chapter has explored The Influence of these factors on the activity of enzyme systems involved in carbohydrate metabolism. Nevertheless, It is worth recalling a few key aspects of carbohydrate Metabolic Regulation.

Glycolysis is a sequence of reactions that converts glucose into Pyruvate. In aerobic organisms, glycolysis serves essentially as a prelude to the tricarboxylic acid (TCA) cycle (Krebs cycle). The ten reactions of glycolysis take place in the Cytosol. The Glycolytic Pathway plays a dual role: it generates ATP through The breakdown of glucose, and it supplies building blocks for the synthesis of cellular components. Under physiological conditions, the Reactions of the glycolytic pathway are readily reversible, except for those catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase. Phosphofructokinase is the most critical regulatory enzyme in glycolysis; it is inhibited by high concentrations of ATP and citrate, and activated by AMP.

The Tricarboxylic Acid Cycle (Krebs cycle) represents the final common pathway for The oxidation of fuel molecules. Most fuel molecules enter the cycle in the form of acetyl-CoA. The oxidative decarboxylation of pyruvate, which yields acetyl-CoA, serves as the linking bridge between glycolysis and the tricarboxylic acid cycle. Notably, the latter also acts as a source of precursors for biosynthetic processes. All reactions of the cycle take place within the Cell/35.html">Mitochondria.

The rate of the tricarboxylic acid cycle depends on the cellular demand for ATP. A high cellular energy charge suppresses the activity of citrate synthase, isocitrate dehydrogenase, and a-ketoglutarate dehydrogenase. Another important regulatory checkpoint is the irreversible Formation of Acetyl-CoA from pyruvate. The pentose phosphate pathway generates NADPH and ribose-5-phosphate in the cytosol. NADPH participates in reductive biosyntheses, whereas ribose-5-phosphate is utilized in the synthesis of RNA, DNA, and nucleotide coenzymes.

The interplay between the glycolytic and Pentose Phosphate Pathways ensures the continuous adjustment of NADPH, ATP, and building block concentrations—such as ribose-5-phosphate and pyruvate—to meet the physiological needs of Cells.

Finally, Gluconeogenesis and glycolysis are reciprocally regulated, meaning that when the activity of one pathway relatively decreases, the activity of the other increases.

In humans and animals, at all stages of carbohydrate Synthesis and Breakdown, the REGULATION OF CARBOHYDRATE Metabolism is mediated by the Central Nervous system (CNS) and Hormones.

For instance, it has been established that a Blood glucose concentration falling below 3.3–3.4 mmol/L (60–70 mg/100 mL) triggers a reflex excitation of the higher metabolic centers located in the Hypothalamus. A particularly crucial role in The regulation of carbohydrate metabolism belongs to the highest level of the CNS—the Cerebral Cortex. Along with the CNS, hormonal factors exert a significant influence on blood glucose levels, meaning that Blood Glucose Regulation is ultimately coordinated by the CNS acting through various Endocrine glands (see Chapter 8).