Metabolism Of Carbohydrates Biochemistry Notes-III

Afza.Malik GDA

Carbohydrates Metabolism Biochemistry for Nurses

Metabolism Of Carbohydrates Biochemistry Notes-III

Energy Yield Per Glucose Molecule Oxidation,In Glycolysis in Presence of O2 (Aerobic Phase),Clinical Importance,Regulation Of Glycolysis, Formation And Fate Of Pyruvic Acid,Formation of Pyruvic Acid (PA) in the Body, Pyruvic acid is a key substance in phase-II metabolism.,Fate of Pyruvic Acid (PA).

Energy Yield Per Glucose Molecule Oxidation
In Glycolysis in Presence of O2 (Aerobic Phase)

Reaction catalysed by

Stage I

1. Hexokinase/Glucokinase reaction (for phosphorylation) – 1 ATP

2. Phosphofructokinase-1 (for phosphorylation) – 1 ATP

Stage III

3. Glyceraldehyde-3-P dehydrogenase (oxidation of 2 NADH in electron transport chain) + 6 ATP

4. Phosphoglycerate kinase (substrate level phosphorylation) + 2 ATP 

Stage IV

5. Pyruvate kinase (substrate level phosphorylation) + 2 ATP Net gain = 10–2 = 8 ATP

B. In Glycolysis—in Absence of O2 (Anaerobic Phase)

• In absence of O2, reoxidation of NADH at glyceraldehyde-3-P-dehydrogenase stage cannot take place in electron-transport chain.

• But the cells have limited coenzyme. Hence to continue the glycolytic cycle NADH must be oxidised to NAD+. This is achieved by reoxidation of NADH by conversion of pyruvate to lactate (without producing ATP) by the enzyme lactate dehydrogenase.

• It is to be noted that in the reaction catalysed by glyceraldehyde-3-P-dehydrogenase, therefore, no ATP is produced.

In anaerobic phase per molecule of glucose oxidation 4 – 2 = 2 ATP will be produced.

Clinical Importance

• Tissues that function under hypoxic circumstances will produce lactic acid from glucose oxidation, producing local acidosis. If lactate production is more it can produce metabolic acidosis.

• Vigorously contracting skeletal muscle will produce relative anaerobiosis and glycolysis will produce lactic acid.

• Whether O2 is present or not, glycolysis in erythrocytes always terminate in pyruvate and lactate.

• When there is relative anaerobiosis, glycolysis will stop as cells will exhaust NAD+.

• Inhibitor of Lactate Dehydrogenase (LDH) is Oxamate: It competitively inhibits lactate dehydrogenase and prevents the reoxidation of NADH.

Regulation Of Glycolysis
Regulation of glycolysis achieved by three types of mechanisms:

(a) Changes in the rate of enzyme synthesis, Induction/ repression.

(b) Covalent modification by reversible phosphorylation.

(c) Allosteric modification.

(a) Induction and repression of key enzymes: This is not rapid and takes several hours to come into operation.

• Glucose: When there is increased substrate, i.e. glucose, the enzymes involved in utilisation of glucose are activated. On the other hand, enzymes responsible for producing glucose (gluconeogenesis) are inhibited. Glucose also increases the activity of the key enzymes glucokinase, phosphofructokinase-1 and pyruvate kinase.

• Insulin: The secretion of insulin which is responsive to blood glucose concentration enhances the synthesis of the key enzymes responsible for glycolysis. On the other hand, it antagonises the effects of glucocorticoids and glucagon-stimulated c-AMP in stimulating the key enzymes responsible for gluconeogenesis.

(b) Covalent modification by reversible phosphorylation: Hormones like epinephrine and glucagon which increase cAMP level activate cAMP-dependant Protein kinase which can phosphorylate and inactivate the Key enzyme Pyruvate kinase and, thus, inhibit glycolysis. This is a rapid process and occurs quickly.

(c) Allosteric modification: Phosphofructokinase-1 is the Key regulatory enzyme and is subject to “feedback” control.

• Inhibition of the enzyme: The enzyme is inhibited by citrate and by ATP.

• Activator of the enzyme: The enzyme is activated by AMP.

• AMP acts as the indicator of energy status of the cell: When ATP is used in energy requiring processes resulting in formation of ADP, the concentration of AMP increases. Normally ATP concentration may be fifty times that of AMP concentration at equilibrium, a small decrease in ATP concentration will cause a several fold rise in AMP concentration. 

    Thus a large change in AMP concentration acts as a metabolic amplifier of a small change in ATP concentration. The above mechanism allows the activity of the enzyme phosphofructokinase-1 to be highly sensitive to even small changes of energy status of the cell and hence it controls the amount of glucose that should undergo glycolysis prior to its entry as acetyl-CoA in TCA cycle.

• In hypoxia: The concentration of ATP in the cells decreases and there is increase in concentration of AMP which explains why glycolysis should increase in absence of O2.

Formation And Fate Of Pyruvic Acid
Formation of Pyruvic Acid (PA) in the Body

• From oxidation of glucose (Glycolysis)

• From lactic acid by oxidation

• Deamination of Alanine

• Glucogenic amino acids-pyruvate forming

• Decarboxylation of oxaloacetic acid (OAA)

Pyruvic acid is a key substance in phase-II metabolism.

1. Principally it is formed from oxidation of glucose (glycolysis) by EM Pathway. In addition to that pyruvic acid can be formed in the body from various other sources. They are:

2. Conversion of lactic acid to pyruvic acid (see below).

3. Also formed from deamination of amino acid alanine.

4. Certain other amino acids during their catabolism produces pyruvic acid, e.g. glycine, serine, cysteine/ and cystine and threonine (Glucogenic a-a).

5. Pyruvic acid can also be formed from decarboxylation of dicarboxylic ketoacid oxaloacetic acid, which can be spontaneous decarboxylation or can be catalysed by the enzyme oxaloacetate decarboxylase.

6. Lastly pyruvic acid can be formed in the body from malic acid by malic enzyme.

Fate of Pyruvic Acid (PA)

• Forms acetyl-CoA by oxidative decarboxylation (in presence of O2)

• Forms lactic acid by reduction (in absence of O2)

• Forms alanine by amination

• Forms glucose (gluconeogenesis)

• Forms malic acid → to OAA (oxaloacetic acid)

• Forms oxaloacetic acid (OAA) by CO2-fixation reaction.

• Pyruvic acid can be aminated to form the amino acid alanine

• Pyruvic acid can be converted to form glucose in the body

• Pyruvic acid can be converted to malic acid, which in turn can form oxaloacetic acid (OAA)

• Pyruvic acid can be converted directly to oxaloacetic acid in the body by CO2-fixation (CO2-assimilation) reaction.

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