Carbohydrates metabolism. Intermediate and final stages of carbohydrates metabolism

Gluconeogenesis and Cori cycle

Gluconeogenesis is a process of formation of glucose from intermediates. This process occurs mainly in liver and kidneys and it is considered as opposite directed reactions of anaerobic glycolysis, because reactions of anaerobic glycolysis are reversible. Only 3 reactions of anaerobic glycolysis are irreversible. These are reactions catalyzed by hexokinase, phosphofructokinase and pyruvatekinase. Another enzymes of gluconeogenesis catalyze these reactions. Hence, there are 3 round-way reactions of gluconeogenesis. These include formation of phosphoenolpyruvate; fructoso-6-phosphate from fructoso-1,6-diphosphate and glucose from glucose-6-phosphate.

1-st specific reaction of gluconeogenesis (1-st round way): formation of phosphoenolpyruvate.

2-nd reaction: fructoso-1,6-diphosphate is dephosphorylated and forms fructoso-6-phosphate.

Fructoso-6-phosphate is converted to glucoso-6-phosphate

3-rd reaction: glucoso-6-phosphate is dephosphorylated and glucose is formed

The importance of gluconeogenesis:

1. formation of glucose when deficiency of its is observed, e.g. in starvation

2. maintenance of homeostasis: pyruvate, lactate, glycogenic amino acids are converted to glucose. In some diseases of liver and kidneys gluconeogenesis is destroyed and lactate is increased in blood. It results in acidosis

Cori cycle and its role

Glycogenolysis, glycolysis and gluconeogenesis comprise intercommunicated system for maintenance of homeostasis and form Cori cycle:

Table 8. Cori cycle

Liver	Blood	Muscles
Gl-6-phglucose Gluconeogenesis 2 Lactate	Glucose 3.4-6.1mM/l  <--2 Lactate	Gl-6-ph (2847 kJ) Glycolysis2 ATP (210kJ) <--2 Lactate (2637 kJ)

The importance of Cori cycle consists in conservation of energy-riched lactate. Lactate isn’t lost, but it is converted to glucose.

Aerobic oxidation of glucose and its energetic value

The oxidation of glucose in aerobic conditions may order in 5 stages:

1. oxidation of glucose to pyruvate

2. oxidative decarboxylation of pyruvate to acetylCoA

3. usage of acetylCoA in citric acid cycle to NADH2, FPH2 and ATP

4. biologic oxidation, where energy and endogenic water are formed

5. oxidative phosphorylation in which ATP is formed

Thus, glucose is oxidized to pyruvate in anaerobic conditions. Pyruvate may be used in carboxylation and transamination.

Energetic value of aerobic glycolysis

4-2 = 2 ATP

Cytosolic NADH2 are oxidized through glycerophosphate’s and malate’s shunts.

Glycerophosphate’s shunt

2DOAP+2NADH22phosphoglycerate+2NAD (in cytosol)

2phosphoglycerate+2FAD2DOAP +2FADH2 (in mitochondrions), each FADH gives 2x2=4ATP

Malate’s shunt

2oxaloacetic acid+2NADH22malate+2NAD (in cytososl)

2malate+2NAD2oxaloacetic acid +2NADH2 (in mitochondrions), each NADH2 gives 2x3=6 ATP

Thus, energetic value of aerbic oxidation of glucose makes up 36 ATP (in the case of glycerophosphate’s shunt) or 38 ATP in the case of malate’s shunt.

Pentose phosphate’s cycle

This process occurs in cytosol with participation of many enzymes in anaerobic conditions. A main enzyme is glucose-6-phosphate dehydrogenase (with coenzyme NADPH2):

1) 6glucose-6-phosphate+12NADPH212NADP+6Pentose-5-phosphate+6CO2 (glucose-6-phosphate-dehydrogenase)

2) 6Pentose-5-phosphate4frucose-6-phosphate+2PGA

3) 2PGAfructose-6-phosphate

4) 4frucose-6-phosphate+ fructose-6-phosphate5 fructose-6-phosphate

5) 5 fructose-6-phosphate5glucose-6-phosphate

The importance of PPC:

1. This is a source of NADPH2 for biosynthesis of FFA, cholesterol, ketone bodies, NO etc; hydroxylation reactions; reductive amination, reduction of glutathione and action of NADH-oxidase of blood cells

2. This is a source of pentoses which are used on formation of nucleic acids, coenzymes, nucleoside tri- and diphosphates, GAG

3. This is a way of conversion of pentoses excess to glucose

The resemblance and differences between glycolysis and pentose’s cycle

Both processes occur in cytosol in anaerobic conditions and beginn from phosphorylation of glucose; some intermediates are the same, e.g. fructose-6-phosphate and phosphoglyceraldehyde.

Differences:

Glycolysis:

1. ATP is formed. ATP is a universal source of energy for many processes including proteins biosynthesis etc

2. Glucose is broken up to phosphotrioses. Full cleavage demands oxygen and occurs in mitochondrias;

3. Intermediates of glycolysis may be used for lipids and glucose formation;

4. Glycolysis occurs mainly in muscles

PPC:

1. NADPH2 are formed. They’re sources of energy for biosynthesis of FFA, cholesterol, ketone bodies and corticoids

2. Glucose is completely broken up in anaerobic conditions

3. Intermediates are used for nucleic acids, coenzymes, nucleoside tri- and diphosphates, GAG

4. It occurs in erythrocytes and leukocytes, adipose and nervous tissues, mammary and thyroid glands, liver

Elimination of final products of carbohydrates metabolism

Final products of carbohydrates metabolism are water and CO2. CO2 may be used in carboxylation, e.g. in formation of malonylCoA (2-nd stage of synthesis of FFA).

CO2 is mainly eliminated through lungs. Water is formed in BO and it is used in hydrolysis and hydration. Water is eliminated through kidneys, large intestine, skin and lungs.