Sunday, September 9, 2012

Carbohydrate metabolism

 In carbohydrate metabolism we will study, the types of carbohydrate, how they are digested and absorbed, then we will the cycles of carbohydrate oxidation which generate the energy required for life…. these cycles are:
  1. Glycolysis  = Glucose oxidation (i.e. break down of glucose to get energy).
  2. Frucose metabolism.
  3. Galactose metabolism.
  4. Gluconeogensis = formation of Glucose form non-carbohydrate sources.
  5. Kerbs cycle.
  6. Glycogen Metabolism including breaking and formation of glycogen.
  7. Pentose phosphate pathway = which generate NADH

A) Types of carbohydrates:

1. Monosaccharides
-   They are those carbohydrates that cannot be hydrolyzed into simpler carbohydrates.
-   They may be classified as trioses (3-carbon sugar), tetroses (4-carbon sugar), pentoses (5-carbon sugar), hexoses (6-carbon sugar), or heptoses (7-carbon sugar).
2. Disaccharides:are condensation products of two monosaccharide units. Examples are maltose and sucrose.
3. Oligosaccharidesare condensation products of 2 to 10 monosaccharides; Example: maltotriose
4. Polysaccharidesare condensation products of more than ten monosaccharide units; examples are the starches and dextrins, which may be linear or branched polymers.

B)   Carbohydrate digestion:

After eating, digestion begins as follow:
1) In the mouth, salivary amylase, hydrolyze starch partially into a mixture of dextrins and maltose.
2) In the stomach, salivary amylase continues hydrolysis of starch only for few minutes then stop because the pH becomes acidic due to the presence of the HCl in stomach and this is unfavourable condition for the amylase to work.
3) In the intestine, pancreatic amylase, completes the digestion of starch into maltose with little isomaltose and maltotriose which are then hydrolyzed in the intestine into glucose. Fructose and Galactose.
Starch + H2O   ===== Amylase ====>  Dixterns + Maltose
Dixterns + H2O  ===== Amylase ====> Maltose + Isomaltose + Maltotriose
Maltotriose + H2O ===== Maltase====>Maltose + Glucose
 Maltose + H2O  ======== Maltase====> Glucose + Glucose
Isomaltose + H2O===== Isomaltase====> Glucose + Glucose
Sucrose + H2O========== Sucrase=====>Glucose + Fructose 
Lactose + H2O ========Lactose=======>Glucose + Galactose
4. Sucrose and the enzymes that complete hydrolysis into Monosaccharides presents in the mucus layer of the intestine
5. The net result of carbohydrate hydrolyses is glucose, fructose and Galactose

C) Absorption:

- The polysaccharides and oligosaccharides are not absorbable so, they must be converted to Monosaccharides.
- Monosaccharides are principally absorbed from the duodenum then pass into the blood through the hepatic portal vein to the liver where:
  • Part of these monosaccharides  is stored as glycogen and part is oxidised through glycolysis to obtain energy
  • Part is oxidised through the pentose phosphate pathway to regenerate NADPH which, together with glucose itself, is used in synthesis of such molecules as amino acids, nucleotides, fats and cholesterol
  • Part is oxidised to produce energy (ATP) which is used in the anabolism processes.
Before we know the mechanism by which the glucose is absorbed into the cells we must know the composition of the cell membrane through which the glucose pass.

this part will help any any one who don’t study biology or cell before to be able to understand biochemistry

Composition of the cell membrane:

==>  As from the previous picture, the cell membrane is composed of 2 layers each of them consists of a layer of phospholipids.
==>  Each phospholipid molecule consists of a polar hydrophilic head and a non-polar hydrophobic tail.
==> How the bilayer membrane is formed: And as we knowthe extracellular and intercellular fluid are polar, therefore the polar heads are arranged towards the polar fluids and the non-polar tails arranged toward themselves  inward the membrane where there are a hydrophobic interaction between them and thus forming a phospholipids bilayer membrane
==> And across the membrane there are transport proteins and receptor proteins
==> Function of the cell membrane:-
  • Protection of cells.
  • On the other hand, it represents a barrier which prevents entry of some molecules into cells such as polar molecules but it uses other mechanism by which the molecules enter the cells such as Na-K pump through which ions are transported into the cell.

In case of glucose:

Any polar molecules can’t pass through the inner non-polar layer of cell membrane so, how glucose enter the cell through the cell membrane while it is polar?
===> The answer is that glucose has 2 mechanism to enter the cells:

1) The passive diffusion or transport:

===> DEF: it transport of biochemical and other atomic or molecular substance across the cell membrane into the cell from higher concentration region to a lower concentration region without any need for energy. (i.e. the substance enter the cell only if its concentration outside the cell is more than its concentration inside the cell.)
===> It depends on the concentration gradient.
===> It doesn’t need energy.
===> Depends on the permeability of the cell membrane.
===> Types:
  • Simple diffusion:in which the substance are transported from higher concentration to lower concentration region through the phospholipids bilayer without any need for energy and without using the transmembrane proteins (carriers/transporters/channels/pores).
  • Facilitated diffusion or passive-mediated-transport:in which the substance are transported from higher concentration to lower concentration region through the phospholipids bilayer using the transport proteins  and without any need for energy.
-          Fructose and pentose use this mechanism.
-          Glucose is transported by this mechanism into brain, kidney and liver.

2) Active diffusion or transport

===> DEF: it means transport of a substance from region of lower concentration to a region of higher concentration (i.e. against the concentration gradient) utilizing energy from ATP molecules and carrier proteins.
===> It doesn’t depend on the concentration gradient.
===> It needs energy.
===> This mechanism applied by the cell to accumulate high concentration of molecules that the cell needs such as ions, glucose and amino acids.
===>Doesn’t depend on the permeability of the cell membrane because this mechanism transports the substance through the transport proteins and carrier proteins.
===> It has 2 types:
  • Primary active transport: in which the cell uses chemical energy such as ATP.
  • Secondary active transport: in which the uses electrochemical gradient such as sodium and potassium dependent ATP bump
===> It is the mechanism by which glucose is transported from intestinal tract

Glucose transportation into the cell by insulin action:

===> When the blood glucose level is high, the nervous system sends signals to the beta-cells of the pancreas to secrete insulin.
===> Then insulin binds to its receptors on the outside surface of the cell membrane causing conformational changes to the receptors (where the receptors are soft protein) leading to conformational changes to the cell membrane and opening of protein gates which called glucose transporter (GLUT) leading to entrance of glucose inside the cell.
===> Opening of these gates lead to activation or deactivation of some enzymes that responsible to glucose oxidation.
===> Insulin binding to the receptor is a reversible process because it will leave the receptor after delivering the message.
===> This process is regulated by the central nervous system.
===> Then after the glucose level returns normal; the insulin leave the receptor and no glucose will enter the cell
===> But in some cases the B-cells is highly activated secreting more insulin which make the glucose to enter the cell and  its level is lowered causinghypoglycaemia
===>The receptors of the insulin are specific for insulin and are distributed in all tissue with different concentration where the receptor concentration increases in the tissue:
  • Which utilize glucose as the main source of energy such as brain and cells of the nervous system, red blood cells, muscles,…..etc
  • At which the blood supply is low such as the peripheral tissues.

Some Important Questions:

What is the difference between the receptors and enzymes?

Active site
Just delivering messages sent by the nervous system into the cell (just letter box)
Doesn’t catalyse any reaction
Catalyse reactions and doesn’t deliver any messages.

Why glucose is stored in the liver and muscles as glycogen and not as it is (i.e. glucose)?

Because glycogen is solid polymer that is compacted and occupy a small size inside the cell which prevents cell membrane rupture by the pressure on the cell membrane.
While if the glucose is stored as glucose, it will take large size which then cause pressure on the cell membrane and then rupture of the cell membrane.

What is the factor that determines the amount of glucose that enters the cell?

The amount of glucose after meal where the glucose must be maintained at the normal level and the excess must enter the cells

Is the metabolism of fats can be used in formation of glycogen?

The answer is yes because the result of oxidation of fat is formation of glycerol which can enter the gluconeogensis process in which glucose is formed.
So, if glucose can be formed from fats thus glycogen can be form fats

D)  Structure of glucose:

===> Glucose is aldose sugar and has 2 isomers: (D-glucose and L-Glucose)
It has 2 chiral carbon atoms (i.e. the carbon atom that carry 4 different groups); the carbons number 2 and 3
The (L)-glucose is the isomer that is utilized by the cells. WHY?
Because the amino acid molecules which forms the enzyme present in the L- form which make the enzymes in the L- form, therefore the L-glucose is the more suitable substrate which is the more matching with the binding groups in the active site than the D-glucose
Proteins molecules also have L- and D- forms because all has a chiral carbon except glycine which doesn’t carry 4 different groups.

How the scientists classified the isomers into L- and D- forms?

They use the glyceraldehyde as a standard as follow:
-          Each isomer has a chiral carbon (i.e. the carbons atom which carries 4 different groups)
-          The isomer that has L- and D- forms are called enantiomers

Differentiate between the following terms:

1.      Enantiomers:

Are 2 stereoisomers that are mirror images of each other that are “non-superposable” (not identical), much as one’s left and right hands are “the same” but opposite
2.     Epimers:
Epimers are diastereomers that differ in configuration of only one carbon atom and they are non-superposable, and non-mirror images of one another
The glucose molecules are non-mirror image to each other but aren’t identical because they differ in one carbon atom.

3.    Anomers:

In carbohydrate chemistry, an anomer is a special type of epimer because it is a stereoisomer of a cyclic saccharide that differs only in its configuration at the hemiacetal or hemiketal carbon, also called the anomeric carbon
The cyclic structure of glucose has 2 anomers because the hydroxyl groups orientation differes on the hemiketal carbon atom.

------------------------------------------ Best Wishes: Dr.Ehab Aboueladab, Tel:01007834123, ------------------------------------------
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