Biochemistry in Tables, Schemes, and Graphs - S.D. Zhamsaranova 2009

Metabolism and Functions of Carbohydrates
Gluconeogenesis

Gluconeogenesis is the Synthesis of glucose from non-carbohydrate precursors.

Body Glycogen stores are sufficient to meet glucose demands between meals. During carbohydrate deprivation or complete starvation, as well as prolonged physical exertion, Blood glucose concentration is maintained via gluconeogenesis. This process can incorporate any compounds that can be converted into Pyruvate or any other gluconeogenic metabolite. The figure shows the entry points of primary substrates into gluconeogenesis.

Class="center">INCORPORATION OF SUBSTRATES INTO GLUCONEOGENESIS

Primary substrates are utilized in gluconeogenesis under various physiological conditions. For instance, during starvation, a portion of tissue Proteins is degraded into Amino Acids, which are subsequently channeled into gluconeogenesis. Fat breakdown yields glycerol, which enters gluconeogenesis via dihydroxyacetone phosphate. Lactate, produced in Muscles during intense exercise, is converted into glucose in the Liver. Consequently, the physiological roles of gluconeogenesis from lactate versus Amino Acids and glycerol differ. The synthesis of glucose from pyruvate proceeds similarly to Glycolysis, but in the reverse direction.

Up to 80 g of glucose can be synthesized in The Human Body per day. The synthesis of 1 mol of glucose from pyruvate consumes 6 high-energy bonds (4 ATP and 2 GTP).

OVERALL EQUATION FOR GLUCONEOGENESIS FROM PYRUVATE:

2 Пируват + 4ATP + 2GTP + 2(NADH) + 4 Н₂О → Глюкоза + 4ADP + 2GDP + 2NAD⁺ + 6Н₃РО₄

Enzymes: 1 - pyruvate carboxylase, 2 - phosphoenolpyruvate carboxykinase, 3 - fructose-1,6-bisphosphatase, 4 - glucose-6-phosphatase.

Oxaloacetate is formed in the Cell/35.html">Mitochondria, transported into the Cytosol, and channeled into gluconeogenesis.

GLUCOSE-LACTATE CYCLE (CORI CYCLE)

This cycle begins with The production of lactate in muscles via anaerobic glycolysis (particularly in white Muscle fibers, which are relatively poor in mitochondria compared to red fibers). Lactate is transported via the bloodstream to the liver, where it is converted into glucose through gluconeogenesis; this glucose can then be returned via the bloodstream to the working muscle.

GLUCOSE-LACTATE AND GLUCOSE-Alanine CYCLES

THE Pentose Phosphate Pathway IN GLUCOSE METABOLISM

The pentose phosphate pathway of glucose metabolism comprises two phases:

A - oxidative phase

B - non-oxidative phase.

Significance of the pentose phosphate pathway:

a) reduced NADPH is utilized by Cells in reduction and hydroxylation reactions;

b) the pathway supplies The Cell with pentose phosphates required for the synthesis of Nucleic Acids and Coenzymes (NAD, FAD, CoA).

All Reactions of the pentose phosphate pathway take place in the cell cytosol. Some metabolites of the non-oxidative phase are also intermediates of glycolysis. This indicates that the two processes are closely linked, allowing the cell to switch from one pathway to the other depending on its metabolic needs.

DIURNAL FLUCTUATIONS IN BLOOD GLUCOSE CONCENTRATION

Arterial blood glucose concentration is maintained at a steady level of 60 - 100 mg/dL (3.3 - 5.5 mmol/L) throughout the day. Following a carbohydrate-rich meal, blood glucose levels rise several-fold over approximately 1 hour (alimentary hyperglycemia) before returning to baseline.

Legend: A, B - Digestion period; C, D - postabsorptive period. The arrow indicates the time of food intake, and the dashed line represents the normal glucose concentration.

SOURCES OF BLOOD GLUCOSE DURING VARIOUS PERIODS

Legend: 1 - during the digestive period, dietary CARBOHYDRATES serve as the primary source of blood glucose; 2 - in the postabsorptive period, the liver supplies glucose to the blood via Glycogenolysis and gluconeogenesis, with blood glucose levels maintained predominantly through glycogen breakdown for 8–12 hours; 3 - gluconeogenesis and liver glycogen contribute equally to maintaining normal glucose concentration; 4 - over the course of a day, liver glycogen is almost entirely depleted, and The rate of gluconeogenesis increases. Gluconeogenesis is the sole process maintaining blood glucose levels during starvation; 5 - during prolonged starvation, the rate of gluconeogenesis decreases, yet it remains the exclusive source of blood glucose.

LINKAGE OF THE PENTOSE PHOSPHATE PATHWAY OF GLUCOSE METABOLISM WITH GLYCOLYSIS AND GLUCONEOGENESIS

When There is a balanced cellular demand for NADPH and pentoses, the oxidative pathway of pentose synthesis takes place. If the demand for pentoses exceeds The Need for NADPH, the oxidative pathway is bypassed by utilizing glycolytic metabolites: fructose-6-phosphate and glyceraldehyde phosphate are converted into pentoses via non-oxidative reactions. Conversely, if NADPH is required to a greater extent than pentoses, two scenarios are possible:

1) under a high cellular energy status, excess pentoses are converted into fructose-6-phosphate and glyceraldehyde phosphate through the reverse reactions of the non-oxidative pathway, which are then used to synthesize glucose via gluconeogenesis;

2) under a low cellular energy status, pentoses are likewise converted into glyceraldehyde phosphate and fructose-6-phosphate, which subsequently enter glycolysis.