Derived from: Glykys – sweet
Lysis – breakdown/loosing
That is glycolysis means: loosing or splitting of Glucose
Produces energy: -60 KJ/mol.
Occurs: almost in every living cell
Glycolysis takes place in both aerobic and anaerobic organisms
Glycolysis is the central pathway for the glucose catabolism in which glucose (6-carbon compound) is converted into pyruvate (3-carbon compound) through a sequence of 10 steps.
The overall reaction of glycolysis :
C6H12O6 + 2 NAD+ + 2 ADP + 2 P —–> 2 pyruvic acid, (CH3(C=O)COOH + 2 ATP + 2 NADH + 2 H+
Glucose is important fuel for most organisms.
Why is Glucose choosen?
- Glucose is one of the monosaccharides formed formaldehyde under prebiotic conditions
- Glucose has a low tendency to glycosylate proteins
3 different types of chemical transformation take place during glycolysis; their pathways are interconnected:
- Pathway of carbon atoms : Sequence of reactions by which the carbon skeleton of glucose (C6) is degraded to form lactate( C3)
- Pathway of phosphate : sequence of reactions by which inorganic phosphate becomes the terminal phosphate group of ATP
- Pathway of electrons : sequence of oxidoreductions.
Regulatory enzymes of Glycolytic pathway:
- Hexokinase: it phosphorylates a 6-C sugar, a hexose to a hexose phosphate. In most tissues and organisms, glucose is most important substrate of hexokinases, and Glucose -6 – Phosphate, the most important product.
- Phosphofructokinase: it is the most important control element in mammalian glycolytic pathway. It is a allosteric enzyme. It has two conformation states, R and T, that are in equilibrium.
PFK-1: Glycolytic enzymes that catalyses the transfer of a phosphoryl group from ATP to F-6-P to yield ADP and Fructose-1,6-bisphosphate. Mg2+ is important.
PFK-2: Acts on same substrates to yield ADP and Fructose-2,6-bisphosphate. It is a positive modulator of PFK-1.
PFK reaction is strongly exergonic (irreversible) under physiological conditions.
- AMP, ADP
- ATP is both a substrate and an allosteric inhibitor
- Each enzyme subunit has 2 binding sites for ATP, a substrate site, and an inhibitor site
- The substrate site binds ATP equally well in either conformation (R or T); the inhibitor site binds ATP almost exclusively in the T state.
- The other substrates preferentially bind to the R state
- Citrate (intermediate of TCA cycle)
- Fatty acids
- Pyruvate kinase: it generates the ATP and pyruvate by transferring the phosphate group from PEP to ADP. It is an allosteric enzyme
Activated by: fructose 1,6-bisphosphate
Inhibited by: ATP, alanine
Exists as isozymes: L- form: predominates in liver and M- form: mostly in muscles and brain.
Enzymatic steps in detail:
First phase/Primary phase/Preparatory phase/Investment phase
They consume energy to convert the glucose into two 3C sugar phosphates. i.e., phosphorylation of glucose and its conversion to glyceraldehydes-3-phosphate.
In this phase 2 molecules of ATP are invested.
Step 1: Hexokinase
The glucose ring is phosphorylated. Phosphorylation is the process of adding a phosphate group to a molecule derived from ATP. As a result, 1 molecule of ATP has been consumed ( as a substrate). The reaction occurs with the help of the enzyme hexokinase, an enzyme that catalyzes the phosphorylation of many six-membered glucose-like ring structures. Atomic magnesium (Mg) is also involved to help shield the negative charges from the phosphate groups on the ATP molecule. The result of this phosphorylation is a molecule called glucose-6-phosphate (G6P), thusly called because the 6′ carbon of the glucose acquires the phosphate group.
Step 2: Phosphoglucose Isomerase / Phosphohexose Isomerase
This reaction involves an isomerization reaction. The reaction involves the rearrangement of the carbon-oxygen bond to transform the 6-membered ring (aldose sugar) into a 5-membered ring(ketose sugar). six-membered ring opens and then closes in such a way that the first carbon becomes now external to the ring. The reaction is readily reversible, is NOT a rate limiting or regulatory step.
Step 3: Phosphofructokinase
It is a controlled point of glycolysis. Magnesium acts as a cofactor (involved to shield negative charge). In this step, a second molecule of ATP provides the phosphate group that is added on to the F-6-P molecule.
Step 4: Aldolase and Step 5: Triosephosphate isomerase
The enzyme Aldolase splits fructose 1, 6-bisphosphate into two sugars that are isomers of each other. These two sugars are DHAP and GAP. The reaction is reversible, not subjected to regulation.
GAP is the only molecule that continues in the glycolytic pathway. As a result, all of the DHAP molecules produced are further acted on by the enzyme Triosephosphate isomerase (TIM), which reorganizes the DHAP into GAP so it can continue in glycolysis.
TIM has 8 parallel beta and 8 alpha helices (αβ barrel). This structure is also found in Aldolase. Enolase and Pyruvate kinase.
At this point in the glycolytic pathway, we have two 3-carbon molecules, but have not yet fully converted glucose into pyruvate.
Second phase/Secondary phase/Pay-off phase
Oxidation conversion of glyceraldehydes-3-phosphate to Pyruvate and the coupled formation of ATP and NADH.
A total of 2 ATP is put in investment phase, and a total of 4 ATP is made in payoff phase. therefore, net total of 2 ATP.
Step 6: Glyceraldehyde-3-phosphate Dehydrogenase
Two main events take place:
1) glyceraldehyde-3-phosphate is oxidized by the coenzyme nicotinamide adenine dinucleotide (NAD); 2) the molecule is phosphorylated by the addition of a free phosphate group. The enzyme that catalyzes this reaction is glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
The enzyme GAPDH contains appropriate structures and holds the molecule in a conformation such that it allows the NAD molecule to pull a hydrogen off the GAP, converting the NAD to NADH. The phosphate group then attacks the GAP molecule and releases it from the enzyme to yield 1,3 bisphoglycerate, NADH, and a hydrogen atom.
Step 7: Phosphoglycerate Kinase
Magnesium is involved to shield the negative charges on the phosphate groups of the ATP molecule.
This reaction involves the loss of a phosphate group from the starting material. The phosphate is transferred to a molecule of ADP that yields our first molecule of ATP. Since we actually have two molecules of 1,3 bisphoglycerate, we actually synthesize two molecules of ATP at this step. With this synthesis of ATP, we have cancelled the first two molecules of ATP that we used, leaving us with a net of 0 ATP molecules up to this stage of glycolysis.
Step 8: Phosphoglycerate Mutase
Involves a simple rearrangement of the position of the phosphate group on the 3 phosphoglycerate molecule, making it 2 phosphoglycerate. The molecule responsible for catalyzing this reaction is called phosphoglycerate mutase (PGM). A mutase is an enzyme that catalyzes the transfer of a functional group from one position on a molecule to another.
The reaction mechanism proceeds by first adding an additional phosphate group to the 2′ position of the 3 phosphoglycerate. The enzyme then removes the phosphate from the 3′ position leaving just the 2′ phosphate, and thus yielding 2 phsophoglycerate. In this way, the enzyme is also restored to its original, phosphorylated state.
Step 9: Enolase
Enolase works by removing a water group, or dehydrating the 2 phosphoglycerate. The specificity of the enzyme pocket allows for the reaction to occur through a series of steps.
Step 10: Pyruvate Kinase
This reaction involves the transfer of a phosphate group. The phosphate group attached to the 2′ carbon of the PEP is transferred to a molecule of ADP, yielding ATP. Again, since there are two molecules of PEP, here we actually generate 2 ATP molecules.
Steps 1 and 3 = – 2ATP
Steps 7 and 10 = + 4 ATP
Net “visible” ATP produced = 2.
Immediately upon finishing glycolysis, The cell must continue respiration in either an aerobic or anaerobic direction; this choice is made based on the circumstances of the particular cell.
A cell that can perform aerobic respiration and which finds itself in the presence of oxygen will continue on to the aerobic citric acid cycle in the mitochondria.
situation when there is no oxygen (such as muscles under extreme exertion), it will move into a type of anaerobic respiration called homolactic fermentation.
Some cells such as yeast are unable to carry out aerobic respiration and will automatically move into a type of anaerobic respiration called alcoholic fermentation.
Fermentation provide usable energy in the absence of oxygen. And oxidation of carbon remains same and C and H ratio remains same.
The fermentation pathway is common to both aerobic and anaerobic pathways of glucose utilization.
- Under anaerobic conditions
Glucose to fermentated products by fermentation.
- Under aerobic conditions
Glucose to fermentated products by fermentation and then by respiration and presence of oxygen, their occurs CO2 and H2O.
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