Carbohydrates Metabolism Biochemistry for Nurses
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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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