Monday, February 22, 2010

Test 1 BIOC 208

Date: 22 February 2010
Time: 18h00-19h00 (16h00-17h00 for those having STATS Class)
Venue: Life Science Building(Q-Block Extension)
Ground Floor Labs

Total: 60 points
Covers: Chapters 1-4 (Proteins)

GOOD LUCK

Friday, February 19, 2010

Chapter 7: Glycolysis

Metabolism is the set of chemical reactions that happen in living organisms to maintain life.

CATABOLISM AND ANABOLISM
1. Catablosim breaks down large molecules into smaller molecules whereas Anabolism joins small molecules to produces larger molecules.
2. Catabolism produces energy whereas Anabolism requires energy.

For an interactive animation of glycolysis click HERE
Glycolysis is the anaerobic catabolism of glucose.
•It occurs in virtually all cells.
•In eukaryotes, it occurs in the cytosol.
•C6H12O6 + 2NAD+ -> 2C3H4O3 + 2NADH + 2H+
•The free energy stored in 2 molecules of pyruvic acid is somewhat less than that in the original glucose molecule.
•Some of this difference is captured in 2 molecules of ATP.

The Fates of Pyruvic Acid
In YEAST
•Pyruvic acid is decarboxylated and reduced by NADH to form a molecule of carbon dioxide and one of ethanol.
•C3H4O3 + NADH + H+ → CO2 + C2H5OH + NAD+
•This accounts for the bubbles and alcohol in, for examples, beer and champagne.
•The process is called alcoholic fermentation.
•The process is energetically wasteful because so much of the free energy of glucose (some 95%) remains in the alcohol (a good fuel!).

In active MUSCLES•Pyruvic acid is reduced by NADH forming a molecule of lactic acid. •C3H4O3 + NADH + H+ → C3H6O3 + NAD+
•The process is called lactic acid fermentation.
•The process is energetically wasteful because so much free energy remains in the lactic acid molecule. (It can also be debilitating because of the drop in pH as the lactic acid produced in overworked muscles is transported out into the blood.)

In MITOCHONDRIA•Pyruvic acid is oxidized completely to form carbon dioxide and water.
•The process is called cellular respiration. Link to a discussion of cellular respiration.

•Approximately 40% of the energy in the original glucose molecule is trapped in molecules of ATP.

Test yourself:
1. The end product of Glycolysis is:
A) Pyruvate Kinase
B) Phosphoenol pyruvate
C) Glucose
D) Pyruvate

2. Glycolysis occurs in the:
A) Mitochondrion
B) Nucleus
C) Cytoplasm
D) Cell membrane

3. Catabolic processes
A) make complex molecules from simpler ones
B) break complex molecules into simpler ones
C) occur only in autotrophs
D) occur only in heterotrophs
E) none of the above

4. The proper sequence of stages in glycolysis is
A) glucose priming, cleavage and rearrangement, oxidation, ATP generation
B) cleavage and rearrangement, glucose priming, ATP generation, oxidation
C) glucose priming, oxidation, cleavage and rearrangement, ATP generation
D) ATP generation, oxidation, glucose priming, cleavage and rearrangement
E) oxidation, cleavage and rearrangement, ATP generation, glucose priming

5. What substance is regenerated by fermentation?
A) O2
B) NAD+
C) acetyl-CoA
D) ATP
E) glucose

6. The oxidation of glucose to two molecules each of pyruvate, ATP, and NADH is called ________ and occurs in the ________.
A) glycolysis; cytoplasm
B) fermentation; cytoplasm
C) the Krebs cycle; matrix of the mitochondrion
D) anaerobic respiration; cytoplasm
E) the respiratory electron transport chain; cristae of the mitochondrion

7. A cell culture was supplied with radioactively labeled O2. The cells were monitored. In a few minutes the radioactive oxygen atoms were present in which of the following compounds:
A) carbon dioxide
B) NADH and FADH2
C) water
D) ATP
E) lactic acid

8. The final electron acceptor in lactic acid fermentation is:
A) NAD+
B) pyruvate
C) O2
D) lactic acid
E) ATP

9. During the oxidation of glucose, a net gain of ATP only occurs under aerobic conditions.
A) True
B) False

10. ATP formation by glycolysis
A) occurs through aerobic respiration
B) is an extremely efficient method of acquiring energy by the cell
C) requires oxygen
D) involves substrate-level phosphorylation
E) both a and c

Thursday, February 18, 2010

Chapter 6: Carbohydrates

Carbohydrates (also called saccharides) are molecular compounds made from just three elements: carbon, hydrogen and oxygen. Monosaccharides (e.g. glucose) and disaccharides (e.g. sucrose) are relatively small molecules. They are often called sugars. Other carbohydrate molecules are very large (polysaccharides such as starch and cellulose).

Carbohydrates are:• a source of energy for the body e.g. glucose and a store of energy, e.g. starch in plants
• building blocks for polysaccharides (giant carbohydrates), e.g. cellulose in plants and glycogen in the human body
• components of other molecules eg DNA, RNA, glycolipids, glycoproteins, ATP

Monosaccharides
Monosaccharides are the simplest carbohydrates and are often called single sugars. They are the building blocks from which all bigger carbohydrates are made.
Monosaccharides have the general molecular formula (CH2O)n, where n can be 3, 5 or 6.
They can be classified according to the number of carbon atoms in a molecule:
n = 3 trioses, e.g. glyceraldehyde
n = 5 pentoses, e.g. ribose and deoxyribose ('pent' indicates 5)
n = 6 hexoses, e.g. fructose, glucose and galactose ('hex' indicates 6)

There is more than one molecule with the molecular formula C5H10O5 and more than one with the molecular formula C6H12O6. Molecules that have the same molecular formula but different structural formulae are called structural isomers.
Glyceraldehyde's molecular formula is C3H6O3. Its structural formula shows it contains an aldehyde group (-CHO) and two hydroxyl groups (-OH). The presence of an aldehyde group means that glyceraldehyde can also be classified as an aldose. It is a reducing sugar and gives a positive test with Benedict's reagent.
CH2OHCH(OH)CHO is oxidised by Benedict's reagent to CH2OHCH(OH)COOH; the aldehyde group is oxidised to a carboxylic acid and Benedict's reagent is reduced (Cu2+ to Cu+).

Pentoses and hexoses can exist in two forms: cyclic and non-cyclic. In the non-cyclic form their structural formulae show they contain either an aldehyde group or a ketone group.
Monosaccharides containing the aldehyde group are classified as aldoses, and those with a ketone group are classified as ketoses. Aldoses are reducing sugars; ketoses are non-reducing sugars. This is important in understanding the reaction of sugars with Benedict's reagent.
However, in water pentoses and hexoses exist mainly in the cyclic form, and it is in this form that they combine to form larger saccharide molecules.

Glucose
Glucose is the most important carbohydrate fuel in human cells. Its concentration in the blood is about 1 gdm-3. The small size and solubility in water of glucose molecules allows them to pass through the cell membrane into the cell. Energy is released when the molecules are metabolised (C6H12O6 + 6O2 6CO2 + 6H2O). This is part of the process of respiration.
There are two forms of the cyclic glucose molecule: α-glucose and β-glucose.
Two glucose molecules react to form the dissacharide maltose. Starch and cellulose are polysaccharides made up of glucose units.

Galactose
Galactose molecules look very similar to glucose molecules. They can also exist in α and β forms. Galactose reacts with glucose to make the dissacharide lactose.
However, glucose and galactose cannot be easily converted into one another. Galactose cannot play the same part in respiration as glucose.
This comparison of glucose and galactose shows why the precise arrangement of atoms in a molecule (shown by the displayed formula) is so important.

Fructose
Fructose, glucose and galactose are all hexoses. However, whereas glucose and galactose are aldoses (reducing sugars), fructose is a ketose (a non-reducing sugar). It also has a five-atom ring rather than a six-atom ring. Fructose reacts with glucose to make the dissacharide sucrose.

Ribose and deoxyribose
Ribose and deoxyribose are pentoses. The ribose unit forms part of a nucleotide of RNA. The deoxyribose unit forms part of the nucleotide of DNA.

Disaccharides
Monosaccharides are rare in nature. Most sugars found in nature are disaccharides. These form when two monosaccharides react.
A condensation reaction takes place releasing water. This process requires energy. A glycosidic bond forms and holds the two monosaccharide units together.
The three most important disaccharides are sucrose, lactose and maltose. They are formed from the a forms of the appropriate monosaccharides. Sucrose is a non-reducing sugar. Lactose and maltose are reducing sugars.

Disaccharide Monosaccharides
sucrose from α-glucose + α-fructose
maltose from α-glucose + α-glucose
α-lactose * from α-glucose + β-galactose

* Lactose also exists in a beta form, which is made from β-galactose and β-glucose
Disaccharides are soluble in water, but they are too big to pass through the cell membrane by diffusion. They are broken down in the small intestine during digestion to give the smaller monosaccharides that pass into the blood and through cell membranes into cells.
C12H22O11 + H2O C6H12O6 + C6H12O6
This is a hydrolysis reaction and is the reverse of a condensation reaction. It releases energy.

Monosaccharides are used very quickly by cells. However, a cell may not need all the energy immediately and it may need to store it. Monosaccharides are converted into disaccharides in the cell by condensation reactions. Further condensation reactions result in the formation of polysaccharides. These are giant molecules which, importantly, are too big to escape from the cell. These are broken down by hydrolysis into monosaccharides when energy is needed by the cell.

Polysaccharides
Monosaccharides can undergo a series of condensation reactions, adding one unit after another to the chain until very large molecules (polysaccharides) are formed. This is called condensation polymerisation, and the building blocks are called monomers. The properties of a polysaccharide molecule depend on:
• its length (though they are usually very long)
• the extent of any branching (addition of units to the side of the chain rather than one of its ends)
• any folding which results in a more compact molecule
• whether the chain is 'straight' or 'coiled'

Starch
Starch is often produced in plants as a way of storing energy. It exists in two forms: amylose and amylopectin. Both are made from α-glucose. Amylose is an unbranched polymer of α-glucose. The molecules coil into a helical structure. It forms a colloidal suspension in hot water. Amylopectin is a branched polymer of α-glucose. It is completely insoluble in water.

Glycogen
Glycogen is amylopectin with very short distances between the branching side-chains. Starch from plants is hydrolysed in the body to produce glucose. Glucose passes into the cell and is used in metabolism. Inside the cell, glucose can be polymerised to make glycogen which acts as a carbohydrate energy store.

Cellulose
Cellulose is a third polymer made from glucose. But this time it's made from β-glucose molecules and the polymer molecules are 'straight'.
Section of a cellulose molecule

Cellulose serves a very different purpose in nature to starch and glycogen. It makes up the cell walls in plant cells. These are much tougher than cell membranes. This toughness is due to the arrangement of glucose units in the polymer chain and the hydrogen-bonding between neighbouring chains.
Cellulose is not hydrolysed easily and, therefore, cannot be digested so it is not a source of energy for humans. The stomachs of Herbivores contain a specific enzyme called cellulase which enables them to digest cellulose.

REDUCING SUGARSA reducing sugar is any sugar that, in an alkaline solution, forms some aldehyde or ketone. This allows the sugar to act as a reducing agent, for example in the Maillard reaction and Benedict's reaction.
Examples
Reducing sugars include glucose, fructose, glyceraldehyde, lactose, arabinose and maltose. All monosaccharides which contain ketone groups are known as ketoses, and those which contain aldehyde groups are known as aldoses.
Also in glucose polymers as glucose syrup, maltodextrin and dextrin the macromolecule, begins with a reducing sugar, a free aldehyde. The more hydrolysed starch, the shorter molecule, the more reducing sugars are present. The percentage reducing sugars present in these starch derivatives is called dextrose equivalent (DE).
Significantly, sucrose and trehalose are not reducing sugars.

Chemistry of reducing sugars
A reducing sugar occurs when its anomeric carbon (the carbon which is linked to two oxygen atoms) is in the free form. Since sugars occur in a chain as well as a ring structure, it is possible to have an equilibrium between these two forms. When the hemi-acetal or hemi-ketal hydroxyl group is free, i.e. it is not locked in an acetal or ketal linkage, the aldehyde or ketone (i.e. the chain-form) is present. The aldehyde can be oxidized to a carboxyl group via a redox reaction. The chemical that causes this oxidation becomes reduced. Thus, a reducing sugar is one that reduces certain chemicals. Even though a ketone cannot be oxidized directly, a keto sugar can sometimes be converted to an aldehyde via a series of tautomeric shifts to migrate the carbonyl to the end of the chain. Therefore, keto sugars are also sometimes reducing.



Test your knowledge
1. Saccharides contain the following combination of elements:
A. carbon, nitrogen and hydrogen
B. carbon, hydrogen and phosphorus
C. carbon and hydrogen
D. carbon, oxygen and hydrogen

2. Aldoses are reducing sugars because in their non-cyclic form they contain:
A. an ester group
B. a ketone group
C. an aldehyde group
D. an hydroxyl group

3. Which is the most important carbohydrate fuel in human cells?
A. ribose
B. glucose
C. fructose
D. galactose

4. Which two monosaccharides combine to form sucrose?
A. α-galactose and α-fructose
B. α-fructose and α-ribose
C. α-glucose and β-glucose
D. α-glucose and α-fructose

5. The type of reaction that occurs when a disaccharide is formed from two monosaccharides is
A. reduction
B. addition
C. hydrolysis
D. condensation

6. The type of bond that forms when a disaccharide is formed from two monosaccharides is called:
A. a peptide bond
B. a carbohydrate bond
C. an ester bond
D. a glycosidic bond

7. The products of hydrolysis of lactose are:
A. α-glucose and α-fructose
B. α-galactose and α-ribose
C. α-fructose and α-galactose
D. α-glucose and α-galactose

8. Starch is a polymer made from the following monomer:
A. α-glucose
B. β-glucose
C. α-fructose
D. α-galactose

Wednesday, February 17, 2010

How TB challenges the host (Try answering)



I was attending a Colloquim on Innate Immunity in Johannesburg on Monday and Tueday 15-16 Feb and here is a scenario that you will find interesting. The figure above shows how TB is attacked by the cells of the immune system in an attempt to kill it. TLR4 is a protein on cells and it binds TB bacteria using the extracellular component and once this is achieved, Protein A binds the intracellular domain of TLR-4, leading to internalization and killing of TB.

Try these Questions:
1. Which of the two strains of TB is likely to be killed in this way. Study the amino acid composition of the structures to make your argument.
2. TLR4 has 3 components: the extracellular domain, transmembrane domain, and intracellular domain. Each of the domains has different amino acid composition. Can you comment on the relevance of these differences in structure.
3. TB is ultimately supposed to be killed by an enzyme called Lysozyme at pH2. If lysozyme is rich in Tryptophan, why would a pH of 2 be required?
4. What type of amino acids would you expect to find dominating Protein A.
5. If you were to design a drug that could directly kill TB, what kind of drug would you design (look at the amino acid composition of TB to guide you).