Digestion Metabolism Part 2

Glycolysis: 

  • Glyco - Glucose +  Lysis - Breakdown = Sugar Splitting.

  • The metabolic pathway that breaks down glucose to produce energy.

  • Occurs in the Cytoplasm because this is where the glucose and enzymes are located that are involved in glycolysis. It is an anaerobic type of respiration performed by all cells.

  • And mitochondria is also anabolic involving oxidative phosphorylation.


Glycolysis Process:

  • 2 phases, Investment Phase (Preparatory Phase)  and Pay-Off Phase


  1. Investment Phase

  • Consumes energy (ATP and NAD+) to convert glucose into two molecules of three carbon-sugar phosphate. Consists of the first 5 steps of Glycolysis.

  • To breakdown glucose


  1. Payoff Phase 

  • The second half of glycolysis. From the two triose sugars in the preparatory phase, each reaction in the pay-off phase occurs twice per glucose molecule. It will now yield 2 NADH molecules and 4 ATP molecules. 


Intermediate Products: GGFFGDB23PP

  • Glucose

  • Glucose-6-Phosphate

  • Fructose-6-Phosphate

  • Fructose-1,6-Bisphosphate

  • Glyceraldehyde-3-Phosphate

  • Dihydroxyacetone Phosphate

  • 1-3-Bisphospho-Glycerate

  • 3-Phospho-Glycerate

  • 2-Phospho-Glycerate

  • Phosphoenol-Pyruvate

  • Pyruvate


Enzymes: HPATGPPEP

  • Hexokinase =  first enzyme involved in Glycolysis converts Glucose to Glucose-6-Phosphate

  • Phosphoglucose Isomerase = converts Glucose-6-Phosphate to Fructose-6-Phosphate

  • Phosphofructokinase-1 = converts Fructose-6-Phosphate to Fructose-1-6-Bisphosphate

  • Aldolase = converts Fructose-1,6-Bisphosphate to Glyceraldehyde-3-Phosphate and Dihydroxyacetone Phosphate by the enzyme 

  • Triose-Phosphate Isomerase =  catalyzes the isomerization of Glyceraldehyde-3-Phosphate to Dihydroxyacetone Phosphate and vice versa; acts on three carbon compounds.

  • Glyceraldehyde-3-Phosphate Dehydrogenase = converts Glyceraldehyde-3-Phosphate to 1-3-Bisphospho-Glycerate

  • Phosphoglycerate Kinase = catalyzes the conversion of 1-3-Bisphospho-Glycerate to 3-Phospho-Glycerate

  • Phosphoglycerate Mutase = 3-Phospho-Glycerate to 2-Phospho-Glycerate

  • Enolase - 2-Phospho-Glycerate to Phosphoenol-Pyruvate

  • Pyruvate Kinase - enzyme for the last step of glycolysis 


Terminologies:


Isomerase:  

- General class of enzymes that convert a molecule from one isomer to another. 


Isomers:

-  Are molecules or polyatomic ions with identical molecular formulas, same number of atoms of each element, but have distinct arrangements of atoms in space


Phase 1: Investment Phase


Step 1: A molecule of glucose enters the cytosol and is converted to glucose-6-phosphate. It is catalyzed by hexokinase. (ATP TO ADP)


Hexokinase came from the words: Hexo - Six (for the six carbon compound glucose); Kinase - group of enzymes that catalyze phosphorylation reactions. 


The process of Phosphorylation happens. Hexokinase transfers one molecule of phosphate to glucose resulting in glucose-6-phosphate. The phosphate group is from ATP (3 phosphate group) which is converted to a molecule of ADP (2 phosphate group), meaning it uses up one molecule of ATP.


Step 2: Glucose-6-Phosphate is converted to Fructose-6-Phosphate by the enzyme Phosphoglucose isomerase, this is simply a rearrangement reaction.


The isomerisation step is responsible for creating the form of the molecule able to yield 2 three-carbon compounds, while the subsequent phosphorylation is important so that fructose-6-phosphate will not isomerise back to glucose-6-phosphate.



Step 3: Fructose-6-Phosphate is converted to Fructose-1,6-Bisphosphate. It is catalyzed by the enzyme phospho-fructokinase-1.  (ATP TO ADP)


The process of Phosphorylation again happens. Phospho-fructokinase-1 transfers one molecule of phosphate to Fructose-6-Phosphate resulting in Fructose-1,6-Bisphosphate. The phosphate group is from ATP (3 phosphate group) which is converted to a molecule of ADP (2 phosphate group), meaning it uses up one molecule of ATP.


Step 4: The Fructose-1,6-Bisphosphate is split into two molecules; Glyceraldehyde-3-Phosphate and Dihydroxyacetone Phosphate and is catalyzed by the enzyme Aldolase. 


Step 5: Dihydroxyacetone Phosphate gets converted to Glyceraldehyde-3-Phosphate through the enzyme Triose Phosphate Isomerase (3 Carbon Sugar). We will now have two G3P molecules.


Chemical Relationship: 3 Carbons, 5 Hydrogen atoms, Six Oxygen atoms, and a Phosphorus atom. = Isomers.


Glyceraldehyde-3-Phosphate and Dihydroxyacetone Phosphate are isomers and can be converted into each other by the enzyme isomerase.


Glyceraldehyde-3-Phosphate is more utilized in glycolysis, the equilibrium of the isomerization reaction is towards the Glyceraldehyde-3-Phosphate.


Phase 2: Payoff Phase


Every molecule of glucose is split into two molecules so every reaction in the second phase happens twice and produces two products.


Step 6: The Glyceraldehyde-3-Phosphate is oxidized into 1-3-Bisphospho-Glycerate, catalyzed by the enzyme Glyceraldehyde-3-Phosphate Dehydrogenase. (NAD+ TO NADH)


Removed a Hydrogen from Glyceraldehyde-3-Phosphate and added an Oxygen in 1-3-Bisphospho-Glycerate.


Here the coenzyme Nicotinamide Adenine Dinucleotide (NAD+) is reduced (adding the Hydrogen) to NADH. Which is further utilized in the electron transport chain to produce more energy.


An addition of a phosphate group in the first position of the Phosphoglycerate occurs here. It will now have two phosphate groups. 1-3-Bisphospho-Glycerate.


This reaction utilizes a molecule of inorganic phosphate. 


Step 7: The 1-3-Bisphospho-Glycerate is converted to 3-Phosphoglycerate by the enzyme Phosphoglycerate Kinase. (ADP TO ATP)


The enzyme transfers the position of the phosphate group to the first position of phosphoglycerate to ADP, a molecule of ATP will be generated in this process.


The enzyme transfers the position of the phosphate group to ADP converting it to ATP. The process is called Substrate level phosphorylation, the formation of ATP by a phosphate group transfer.


In the payoff phase everything must be multiplied by two. So 2 ADP is consumed to make 2 ATP.


Step 8: 3-Phospho-Glycerate is converted to 2-Phospho-Glycerate, it is a rearrangement reaction aided by the enzyme Phosphoglycerate Mutase. 


Mutase - type of isomerase enzyme whose purpose is to move a functional group to another.


Step 9: 2-Phospho-Glycerate is converted to Phosphoenol-Pyruvate through the enzyme Enolase.


Dehydration reaction - removing water from the equation.

Phospho - Phosphate Group

Enol - Alcohol attached to Alkene

Enolase - reaction proceeds to an enolic intermediate so the enzyme helps to facilitate the process.


Water becomes a product.


Step 10: Phosphoenol-Pyruvate is converted to Pyruvate by the enzyme Pyruvate Kinase. The phosphate group at the Phospho-Enol Pyruvate is converted to ADP and then converted to ATP. (ADP TO ATP)


The enzyme transfers the position of the phosphate group to ADP converting it to ATP. The process is called Substrate level phosphorylation, the formation of ATP by a phosphate group transfer.


In the payoff phase everything must be multiplied by two. So 2 ADP is consumed to make 2 ATP.


Cofactors needed in this step are Magnesium and potassium ions


Net Reaction of Glycolysis:

Glucose + 2 ADP + 2 Pi + NAD+ = 2 Pyruvate + 2 ATP + 2 NADH


  • 1 molecule of 6 Carbon compound Glucose splits to 2 molecules of 3 Carbon compound Pyruvates. 

  • 2 ADPs are produced in the 1st phase (Step 1 and 3) and 4 ADP are used in the 2nd phase (Step 7 and 10), there is a net use of 2 ADP.

  • 2 Molecules of inorganic phosphate are utilized in phase 2 (Step 6)

  • 2 NAD+ are reduced to 2 NADH molecules (Step 5)


Glucose = 2 Pyruvate

4 ATP formed - 2 ATP used = 2 ATP

2 NAD+ + 4 e- + 4 H+ = 2 NADH


Phase 1 - uses up 2 ATP (Step 1 and 3), reduces NADP+

Phase 2 - produces 4 ATP (Step 7 and 10); 2 NADH


Significant Steps

Steps 1 3 6 7 10




Step 1: A molecule of glucose enters the cytosol and is converted to Glucose-6-Phosphate. It is catalyzed by the enzyme Hexokinase.


The process of Phosphorylation happens. Hexokinase transfers one molecule of phosphate to glucose resulting in glucose-6-phosphate. The phosphate group is from ATP (3 phosphate group) which is converted to a molecule of ADP (2 phosphate group), hence it uses up one molecule of ATP.


Step 2: Glucose-6-Phosphate is converted to Fructose-6-Phosphate by the enzyme Phosphoglucose isomerase, a rearrangement reaction is what occurs here.


Step 3: Fructose-6-Phosphate is converted to Fructose-1,6-Bisphosphate. It is catalyzed by the enzyme phospho-fructokinase-1. 


The process of Phosphorylation again happens on this step. Phospho-fructokinase-1 transfers one molecule of phosphate to Fructose-6-Phosphate resulting in Fructose-1,6-Bisphosphate. The phosphate group is from ATP (3 phosphate group) which is converted to a molecule of ADP (2 phosphate group), hence it uses up one molecule of ATP.


Step 4: The Fructose-1,6-Bisphosphate is split into two molecules; Glyceraldehyde-3-Phosphate and Dihydroxyacetone Phosphate and is catalyzed by the enzyme Aldolase. 


Step 5: Dihydroxyacetone Phosphate gets converted to Glyceraldehyde-3-Phosphate through the enzyme Triose Phosphate Isomerase (3 Carbon Sugar). There are now two G3P molecules.


Chemical Relationship: 3 Carbons, 5 Hydrogen atoms, Six Oxygen atoms, and a Phosphorus atom. = Isomers.


Glyceraldehyde-3-Phosphate and Dihydroxyacetone Phosphate are isomers and can be converted into each other by the enzyme isomerase.


Glyceraldehyde-3-Phosphate is more utilized in glycolysis, the equilibrium of the isomerization reaction is towards the Glyceraldehyde-3-Phosphate.


Step 6: The Glyceraldehyde-3-Phosphate is oxidized into 1-3-Bisphospho-Glycerate, catalyzed by the enzyme Glyceraldehyde-3-Phosphate Dehydrogenase. 


Here the coenzyme Nicotinamide Adenine Dinucleotide (NAD+) is reduced (adding the Hydrogen) to NADH. 


Step 7: The 1-3-Bisphospho-Glycerate is converted to 3-Phosphoglycerate by the enzyme Phosphoglycerate Kinase. 


The enzyme transfers the position of the phosphate group to ADP converting it to ATP. The process is called Substrate level phosphorylation, the formation of ATP by a phosphate group transfer.


Step 8: 3-Phospho-Glycerate is converted to 2-Phospho-Glycerate, it is a rearrangement reaction aided by the enzyme Phosphoglycerate Mutase.


Step 9: 2-Phospho-Glycerate is converted to Phosphoenol-Pyruvate through the enzyme Enolase through a dehydration reaction.


Dehydration reaction - removing water from the equation.

Enolase - reaction proceeds to an enolic intermediate so the enzyme helps to facilitate the process.


Step 10: Phosphoenol-Pyruvate is converted to Pyruvate by the enzyme Pyruvate Kinase. The phosphate group at the Phospho-Enol Pyruvate is converted to ADP and then converted to ATP.


The enzyme transfers the position of the phosphate group to ADP converting it to ATP. The process is called Substrate level phosphorylation, the formation of ATP by a phosphate group transfer.