Carbohydrate metabolism

Carbohydrate metabolism as the basis of antioxidant defense

The efficiency of the antioxidant system (AOS) directly depends on the reactions of glucose metabolism. A key link here is the pentose phosphate pathway of its oxidative branch.

• The enzyme glucose-6-phosphate dehydrogenase converts glucose-6-phosphate while simultaneously reducing NADP⁺ to NADPH.
• The generated NADPH acts as a coenzyme for glutathione reductase, which converts oxidized glutathione (GSSG) back to its active reduced form (GSH).
• GSH is required by glutathione peroxidase to neutralize hydrogen peroxide and toxic organic peroxides.

Thus, a continuous chain is formed: carbohydrate metabolism supplies NADPH, which maintains the pool of reduced glutathione that protects cellular structures and proteins (including erythrocyte hemoglobin) from free radical damage. Additionally, methemoglobin reductase participates in these processes, coupling glycolysis with anti-methemoglobinemic defense.

Hyperglycemia and oxidative stress

Chronic elevation of blood glucose and impaired insulin action trigger a cascade of pathological reactions that damage tissues:

1. Type 2 diabetes mellitus: insulin resistance leads to suppression of antioxidant activity, mitochondrial dysfunction, and subsequent cellular apoptosis.
2. Polyol pathway: with excess intracellular glucose and hypercorticism, the sorbitol shunt is activated. The enzyme aldose reductase consumes scarce NADPH, competing with glutathione reductase and critically weakening cellular defense.
3. Protein glycation: excess carbohydrates stimulate the non-enzymatic formation of advanced glycation end products (AGEs), which generate free radicals.

As a result, a pathogenetic vicious circle is formed: hyperglycemia and insulin deficiency increase the production of reactive oxygen species (ROS), which deplete enzymatic and non-enzymatic factors of the AOS, damaging the pancreas and exacerbating metabolic failure.

Laboratory diagnostics and loading tests

To assess the state of carbohydrate metabolism and detect its pathologies, a set of biochemical tests is used:

• Oral glucose tolerance test (OGTT): the patient is given a standard carbohydrate load (1 g of glucose per 1 kg of body weight), and glycemic dynamics are monitored for three hours. Normally, fasting values are 3.3–5.5 mmol/L, and blood sugar levels return to baseline within 2–3 hours.
• Glucagon or adrenaline stimulation test: used when hepatic glycogenoses are suspected (e.g., von Gierke disease). Hormone administration normally rapidly raises glucose levels due to glycogenolysis; this increase is absent in case of an enzymatic block.
• Additional markers: determining lactate, uric acid, and ketone body levels helps differentiate severe metabolic disorders and concomitant diabetic complications.

Class and exam questions

What else to study on this topic

• Metabolic and hormonal regulation of glycogen synthesis and mobilization
• Features of glycogen metabolism in the liver and skeletal muscles
• Molecular mechanisms of stress-response systems and counter-regulatory hormones
• Biochemical manifestations and differential diagnosis of glycogen storage diseases
• The role of non-enzymatic protein glycation and AGEs in the pathogenesis of diabetes

Other topics in the "Additional Topics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.