Carbohydrate metabolism (Glycolysis) – part two

Carbohydrate metabolism

Part Two

In the Carbohydrate metabolism part one, we study carbohydrate digestion and know that the end of digestion is production of Glucose, Fructose and Galactose


Also we know that glucose enters the liver through the hepatic portal vein and glucose should be oxidized through glycolysis
Now we will study glycolysis, but before we continue we need to tell you what is ATP? … this stands for Adenosine Tri-Phosphate which is the Currency of the energy in the cell … HOW? …. This compound contain 3 phosphate groups, each of which produce high energy when it is broken from ATP molecule …. So, when we talk about glycolysis and said that the step 1, for example, consume one phosphate group from ATP molecule, means that this step produce high energy.

Glycolysis

A)  Definition:

It is the breakdown of glucose in the cell cytosol (= cytoplasm) producing pyrurate in the presence of oxygen or lactate in the absence of oxygen.

B)   Site:

Glycolysis occurs in cytoplasm but:

  • In presence of O2, oxidation of glucose is complete in mitochondria where pyruvate enters the kerb’s cycle and the electron transport chain to complete the oxidation of glucose resulting in a high amount of energy.

  • In absence of O­2, pyruvate is converted into lactate in the cytoplasm giving a small amount of energy but it is important to some tissue.

Therefore:

Occurrence of glycolysis is of physiological importance in:

  1. Tissues with no mitochondria such as RBCs, cornea and lens.

  2. Tissues with few mitochondria: Testis, leucocytes, medulla of the kidney, retina, skin and gastrointestinal tract

  3. Tissues undergo frequent oxygen lack: skeletal muscles especially during exercise….. HOW? …. During hard exercises, muscles need large amount of energy which the Oxygen reach muscles is not enough for it, so, when glucose oxidized through glycolysis and pyruvate is produced and will compete oxidation in absence of oxygen due to the low amount of oxygen and so it will be converted into lactic acid and so the acidity will increase and pH will reduces and the muscle become exhausted …. So, in low oxygen supply or absence of oxygen, cells depends on the glycolysis in the cytoplasm and not on Krebs cycle in mitochondria.

Where they depend only on the glycolysis not on Krebs cycle and the electron transport chain

C)    Stages of glycolysis:

<<<<<<<Stage (I)>>>>>>>

It is the energy requiring stage

In this stage:

  • One molecule of glucose is converted into two molecules of glyceraldehyde-3-phosphate.

  • These steps consume 2 molecules of ATP .

stage-one-glyco

Step one:

1.      Event: (glucose phosphorylation)­

===> A phosphate group is transferred from ATP molecule to the carbon number 6 in the glucose molecule forming glucose-6-phosphate, thus this step is energy consuming.

===> Glucose-6-phosphate is an intermediate forming an important branch point in the metabolism.

===> This step is fast irreversible step

stage-1-step-1

2.  Enzymes stimulating this step:

===> The enzymes used are either glucokinase or hexokinase enzymes which are responsible for entry of glucose into the cell and phosphorylation of glucose which leads to glucose trapping inside the cell …. HOW this trapping occur?? …. The phosphate group that added on the carbon number six on glucose molecule will increase the polarity of glucose and this will make it difficult for glucose to pass through the non-polar part of the cell membrane (see Carbohydrate metabolism part one) and hence glucose is trapped inside the cell and can’t exit through the gates that is opened by insulin, therefore this step is irreversible because if it is reversible the glucose-6-ph will converted back to glucose and could exit from the cell again while the gates is still opened because this gates will be opened until many glucose molecules pass not just one molecule.

===>They are activated after a carbohydrate rich meal for 2 hours to lower the glucose blood level.

NOTE: Kinase enzyme always add phosphate group on the substrate

What is the difference between Hexokinase and glucokinase? (Click here to open)

ٍStep 2:

1.   Event: (formation of fructose-6-phosphate from glucose-6-phosphate)­

Isomerization of glucose-6-phosphate to fructose 6-phosphate, I.e. a conversion of an aldose into a ketose by phosphogluco-isomerase.

It doesn’t need energy because it occurs spontaneosly.

2.   Enzymes stimulating this step: phosphoglucose isomerase.

NOTE: Isomerase enzyme always catalyzes the structural rearrangements.

stage-1-step-2

Step 3:

a.  Event: (Phosphorylation of Fructose-6-phosphate to fructose-1,6-­bisphosphate)­

–  Phosphorylation of Fructose-6-phosphate by ATP to fructose-1,6-­bisphosphate (F-1 ,6-BP)

–   This step is irreversible.

b.  Enzymes stimulating this step: by phosphofructokinase (PFK)

stage-1-step-3

Step 4:

a. Event: (cleave of 6-carbon sugar into two 3-carbon fragments)­

–  Splitting of fructose-1,6-bisphosphate into two 3-carbon fragments:

  • Glyceraldehyde 3-phosphate (GAP)

  • Dihydroxyacetone phosphate (DHAP)

–   Reversible under intracellular conditions

b.  Enzymes stimulating this step:

–  Aldolase. (This enzyme derives its name from the nature of the reverse reaction, an aldol condensation).

stage-1-step-4

Step 5:

a.  Event: (isomerisation of (GAP) to (DHAP))­

–  Isomerisation of Glyceraldehyde 3-phosphate (GAP) to Dihydroxyacetone phosphate (DHAP)

–  It is fast reversible step.

b. Enzymes stimulating this step: triose phosphate isomerase (TPI or TIM).

stage-1-step-5

c.  Importance of this step:

To get full energy from glucose molecules, in other words to get energy from the 6 carbons. EXPLAIN?

  • The cell can’t oxidize DHAP to get energy from it , thus it will be lost as a waste product.

  • Thus, the cell will obtain energy from GAP only (i.e. from 3 carbon of the glucose), not from the 6-carbons.

  • But, the GAP will continue the glycolysis and give energy, while DAHP is not

  • Thus, in order to get energy from the 6-carbons of glucose, the DHAP must be converted to GAP

After this step we get 2 molecules of Glyceraldehyde 3-phosphate (GAP):

One from step 4 and one from step 5.

See Glycolysis stage 2 in page 2

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