Published Paper Review #2

Article: Eiji Furuta, Hiroshi Okuda, Aya Kobayashi, and Kounosuke Watabe^*- Metabolic genes in cancer: their roles in tumor progression and clinical implications; Article accessed on 13^th April, 2013

Metabolic Genes in Cancer

The equilibrium of energy homeostasis in a normal cell is due to three metabolic pathways which include glycolysis, lipogenesis and tricarboxylic acid (TCA) cycle which are in turn closely linked to amino acids. Cells use glucose as its main energy source. Glucose is converted to pyruvate through glycolysis whereas pyruvate is converted to acetyl-CoA which is then used in the TCA cycle in the mitochondria. ATP is generated by TCA via oxidative phosphroylation and citrate is transferred to the cytoplasm which is then converted to acetyl- CoA and used as a substrated for fatty acid generation via the lipogenesis pathway. Fatty acids are used as storage and also as a component in membrane biosynthesis as well as impacting cell signaling by protein modification.

Tumor cells are deemed hypoxic as they re-programme these metabolic pathways. Cancer cells have a high metabolism due to their active proliferation and motile nature. Based on studies and further research, it is believed that tumors rely on non-oxidative energy sources such as glyolysis and as a result tumor progression and tumorigenesis is due to the high number of genes involved in metabolic pathways.

In cancer cells, glucose uptake is significantly increased and oxidation phosphorylation in the mitochondria is significantly decreased. Due to the lack of oxygen and nutrition of the blood supply, rapidly growing cancer cells suffer, glucose metabolism and lactate generation is characteristic of tumor cells which results in hypoxia.

The link between glycolysis and tumorigenesis is a tumor suppressor, P53 which hypothetically blocks the glycolytic pathway through the tumor surpressor and induced glycolysis and apoptosis regulator. This occurs when the glycolytic metabolite fructose-2,6-bis-phosphate is decreased which induces glycolysis and inhibits gluconeogenesis.

Transporter proteins are used in the uptake of glucose across cell membranes. On these transporter proteins there are both amino and carboxy-terminal ends exposed to the cytoplasmic side of the plasma membrane. From the protein family, GLUT1 is found in several different ranges of cancers which include pancreatic, breast, brain and lung to name a few. It acts as an oncogene in cancers which can be mutated and found in high consistencies.

In tumor cells, the re-programming of the lypogenesis pathway is usually a significant alteration. Three genes participate in this process, ATP citrate lyase (ACLY), Acetyl-CoA carboxylase (ACC) and Fatty Acid Synthase (FAS). In FAS, pyruvate is converted to acetyl-CoA in the mitochondria and is then used in the TCA cycle.  Citrate is produced in the presence of sufficient amount of ATP and exported to the cytoplasm where it is catalyzed by ATP citrate lyase (ACLY). Cytosolic acetyl-CoA is then generated which is a key precursor of fatty acids. Acetyl-CoA is then carboxylated by ACC to synthesize malonyl-CoA which is then converted to palmitate (16-carbon saturated fatty acid) as the first fatty acid in lipogenesis by the key rate limiting enzyme.

Citrate is converted to Cytosolic acetyl-CoA by ACLY which is high in tumor cells. ACLY inhibitors block production of acetyl-CoA and consequently suppress cell growth in vitro and in vivo which results in the loss of tumorigenicity in vitro. It can therefore be determined that ACLY contributes to tumorigenesis and tumor cell survival.

The metabolic pathways of cancer cells are said to re-programme during tumors which is due to the alteration of metabolic genes. A high glucose uptake is observed in tumor cells whereas mitochondrial activity seems to be decreased in cancer cells.

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2850259/

Published Paper Review #1

Article: T Alleyne^I; S Roache^II; C Thomas^I; A Shirley^III; The Control of Hypertension by the use of Coconut Water and Mauby: Two Tropical Food Drinks; Article Accessed on 10^th April, 2013

Care For A Drink, Anyone?

Did you know that coconut water and mauby are deemed two beneficial drinks to a healthy, “low-hypertensive” lifestyle?

Hypertension, as we all know is high blood pressure and is due to the elevation of arterial blood pressure which can have detrimental effects on the human body such as heart attacks, aneurysms, renal failure, to name a few. Hypertension is usually caused by smoking, obesity, lack of physical activity and diabetes, high sodium intake, stress or it may be genetically induced.

The Beginning

In the article, “The Control of Hypertension by the use of Coconut Water and Mauby: Two Tropical Food Drinks”, suggested that the consumption of these two drinks can gradually lower hypertension in the body. Various studies show that there is generally a low hypertension count in black populations of Sub-Saharan Africa, as compared to the Western Hemisphere, the USA and the Caribbean, where there is a high hypertension count.  Research has shown that black populations have a higher tendency in developing chronic high blood pressure and that symptoms develop at earlier stages in life.  Many treatments have been futile in attempting to cure this disorder, such as the beta blockers and ACE-Inhibitors. Over the centuries, this chronis disorder has been treated with the use of herbs and natural products, however with the emergence of modern medicines, these practices are now neglected.

Coconut water is used in many tropical countries as an ingredient in foods, and also as a beverage. The immature endosperm, a soft jelly is eaten whereas the dried endosperm is used in the making of pastries such as coconut tart. Cooking oil and margarine are two by-products of the dried endosperm. Based on scientific analysis, coconut water is high in sodium and potassium ions.

Mauby is manufactured from the bark extract of the mauby tree. It is a bitter, dark liquid in the concentrated form, and can be diluted with water and sweetened to taste. The concentrated form of mauby can be used to treat diabetes mellitus.

The Experiment

The study was conducted with the assistance of twenty-eight hypertensive individuals who were divided into four groups. Their systolic and diastolic blood pressures were observed for a period of two weeks before and after the, and once more for another two weeks while undergoing treatment. Group one which was the control, consumed drinking water, group two consumed coconut water, group three consumed mauby, and group four consumed a mixture of both coconut water and mauby.

Individuals studied were from two separate areas in Trinidad, West Indies. Twenty one individuals were from an industrial company in North-western side of the country and the remaining seven were from the St. Augustine Campus, UWI. The study was conducted based on the Declaration of Helsinki and Tokyo and was approved by the Ethics Committee of The University of the West Indies.

For each individual, all observations were recorded at approximately the same time of the day by the same researcher and they were asked to make no changes in their daily routines which ranged from eating habits to antihypertensive medication. The average blood pressures prior to and post the experiment were recoreded for each individual which included the included the highest and lowest values.

Assortment

The individuals were separated into their groups and each person was required to consume 300ml of the designated liquid at two points during the course of the day for the period allotted (two weeks). The careful preparation of the liquids to be consumed was carried out and dispensed into 300ml bottles.

What was the outcome?

For the controlled group, seven out of the eight individuals were found to have a high mean in systolic pressure. However there was no significant difference in the mean of diastolic pressure.

For the group who consumed only the coconut water, seven individuals experienced a decrease in mean of their systolic pressures. Two individuals had significant decreases. As compared to the systolic pressures, there were two cases with significant decrease in the mean of diastolic pressures.

For the group who received mauby, five out of seven individuals were able to complete the study. Two individuals experienced significant decreases in the mean of systolic pressures whereas the two other showed a general decrease and the remaining individual showed an increase in the mean systolic pressure.

Lastly, for the group who received the mixture of coconut water and mauby, there were high significant decreases in both the systolic and diastolic pressure averages as well as high decreases in the diastolic pressure averages.

Conclusion

Consumption of coconut water and mauby mixture resulted in the significant decrease in systolic and diastolic blood pressure averages as compared to the consumption of the separated beverages.

Link: http://caribbean.scielo.org/scielo.php?script=sci_arttext&pid=S0043-31442005000100002&lng=en

Video Review #2-Carbohydrates!

http://www.youtube.com/watch?v=Eqncc6u6Hms&list=PL3993356C72C83C43

Carbohydrates are organic molecules comprised of carbon atoms which are bound to other hydrogen and oxygen atoms. Carbohydrates can be divided into simple sugars and polysaccharides. They have several biochemical roles.

Firstly, they are energy sources, they allow the body to store energy in covalent bonds. For example C-C or C=O. Secondly, they are carbon skeletons which are able to build stuctures important in cell life. Carbohydrates are recognised by the formula (CH2O)n. For example, Hexose contains 6 carbon atoms therefore (CH2O)n would become C6H12O6.

Carbohydrates are divided into:
*Monosaccharides (1 Simple sugar)
*Disaccharides (2 Simple sugars)
*Oligosaccharides (3-20 Simple sugars)
*Polysaccharides (many Simple sugars)

Monosaccharides– 1 monomer include:
*Trioses (C3H6O3) which have 3 carbons, for example Glyceraldehyde and Dihydroxyacetone.
*Pentoses (C5H10O5)- example riboses-Alpha and Beta.
*Hexose such as Glucose (C6H12O6), Fructose, Glactose, Manose.

Disaccharides– 2 monomers bound by glycosidic bond formed by a dehydration reaction or condensation. When a glucose molecule binds to a fructose molecule, there will be a sucrose molecule developed. Lactose is formed by glucose and galactose. When two glucoses bind together, a maltose is formed.
Alpha linkages and beta linkages are found in disaccharides as well as polysaccharides. These glycosidic
linkages are the bonds between two simple sugars within a disaccharide or polysaccharide. Alpha
linkages are easily digested by the human body. Beta linkages are stronger than Alpha linkages
because they are more stable. Carbohydrates with Beta linkages are not easily digested by the
human body, except for lactose because most humans have an enzyme which breaks down this disaccharide.

Polysaccharides are large numbers of sugars joint together resulting in a polymer or macromolecule. There are several which are important to life such as celluose. Cellulose is the main component of the plant cell wall. It’s a linear glucose polysaccharide comprised of β (1–>4) bonds which link the glucose monomers to form fibres of great mechanical strength.

Starch, another essential polysaccharide, acts as the main form of storage for carbohydrates in plants. It is comprise of glucose molecules bound to one another. One of the main forms of starch is amylopectin which has ∝(1–>4)bonds and occasionally has ∝(1–>6) bonds which allow branching.

Glycogen is another essential polysaccharide, used by animal cells and human cells. It is the main form of storage of carbohydrates. Glucose is extracted whenever the body requires energy. This is stored as glycogen in the liver and muscles. Glucose is the monomer for the macromolecule glycogen. It is broken down and used as ATP which is used for metabolism in the body. Glycogen is highly branched.

I hope you enjoyed this video! 🙂 Here’s some facts about glycogen and starch.

A comparison of Starch and Glycogen:
Plants make starch and cellulose through the photosynthesis processes. Animals and human in turn eat plant materials and products. Digestion is a process of hydrolysis where the starch is broken ultimately into the various monosaccharides. A major product is of course glucose which can be used immediately for metabolism to make energy. The glucose that is not used immediately is converted in the liver and muscles into glycogen for storage by the process of glycogenesis. Any glucose in excess of the needs for energy and storage as glycogen is converted to fat.

Video Review #1-Nucleic Acids

This video, I found to be very educational. It’s done by one of three medical students who call themselves “The Salmonella Place”. They do videos based on several aspects of Medicine, Biochemistry being one of them.

The video begins with an introduction of nucleic acids, and their relation to DNA and RNA. A nucleic acid contains a chain of nucleotides linked together with covalent bonds to form a sugar-phosphate backbone with protruding nitrogenous bases. They are linear, biological molecules which are essential to life. The nucleotides are the basic unit of the nucleic acid. These molecules are able to store and express genetic information.

Next in the video, the tutor explains that nucleotides comprise of a nitrogenous Base, Pentose sugar and one to three Phosphates. Pentoses in the nucleic acid include Ribose and Deoxyribose which have bicarbons.

The base of the nucleotide is considered to be heterocyclic which simply means that there are two different rings of atoms- Nitrogen ring and Carbon ring. The base binds at position 1 or Carbon 1. The are two bases in nucleic acids. These are called Purines, which comprise of Adenine (A) and Guanine (G) and Pyridmidines which comprise of Cytosine (C), Thymine (T) and Uracil (U). Cytosine is found in both DNA and RNA, whereas Thymine is found only in DNA and Uracil, only in RNA. Between Adenine and Thymine there are 2 hydrogen bonds and between Guanine and Cytosine there are 3 hydrogen bonds. These are more heat resistant.

The phosphate groups are simply phosphate atoms surrounded by 3 hydroxyl (-OH) groups and an oxygen atom. Phosphate groups can bind both at the 3′ and 5′ position.

As compared to the nucelotide, the nucleoside lacks phosphate but comprises of only a nitrogenous base covalently attached to a pentose (ribose or deoxyribose). The formation of a nucleoside is due to the removal of the phosphate group of a nucleotide via hydrolysis.

He also spoke about a phosphodiester bond which is a covalent bond in RNA or DNA that holds a polynucleotide chain together by joining a phosphate group at position 5 in the pentose sugar of one nucleotide to the hydroxyl group at position 3 in the pentose sugar of the next nucleotide. This is called also a phosphodiester linkage.

Furthermore on nucleotides, they form ATP or Adenosine Triphosphate which is used for energy and storage. Also, they form the Cyclic Adenosine Monophosphate or CAMP which is used for regulatory functions.

Lastly, nucleotides are named after the base component. For example, with the base Adenine, the nuceloside will be Adenosine, Thymine, would be Thymidine. When a nucleotide is named after the base, it is also named after the number of phosphate groups. For example, a nucleoside with 1 phosphate group is called Monophophate such as AMP- Adenosine Monophosphate.

This video was found to be brief and informative, and I do hope you enjoy! 😀

What About The Krebs’ Cycle?

Krebs’ Cycle also known as the Citric Acid Cycle, Tricarboxylic acid cycle (TCA cycle) or the Szent-Györgyi–Krebs cycle which  is a series of enzyme-catalyzed chemical reactions that form a key part of aerobic respiration in cells. It occurs in the matrix of the mitochondria and is used by all aerobic organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and proteins into carbon dioxide. 

In this cycle, Acetyl-CoA splits into CoA which is reused in the link reaction and into an acetyl group. This 2-carbon acetyl group enters the Krebs’ cycle by combining with oxaloacetate. When they react they form a 6-carbon citrate compound. During the Krebs’ cycle a series of decarboxylation reactions and dehydrogenation reactions occur. Hydrogens (H) are accepted by NAD which becomes NADH and Flavine Adenine Dinucleotide (FAD) which becomes FADH. FADH and NADH transport the H atoms to the respiratory chain where large amounts of ATP are manufactured. It is important that oxaloacetate is continuously regenerated in the cycle to ensure that it combines with and acetyl group and enables the removal of H from various intermediates in the Krebs’ cycle. The cycle is split into eight steps.

 Step 1

The acetic acid subunit of acetyl CoA is combined with oxaloacetate to form a molecule of citrate.  The Acetyl-CoA acts only as a transporter of acetic acid from one enzyme to another.  After Step 1, the coenzyme is released by hydrolysis so that it may combine with another acetic acid molecule to begin the Krebs cycle again.

Step 2

The citric acid molecule undergoes an isomerization. A hydroxyl group and a hydrogen molecule are removed from the citrate structure in the form of water. The two carbons form a double bond until the water molecule is added back. The hydroxyl group and hydrogen molecule are reversed with respect to the original structure of the citrate molecule. Thus, isocitrate is formed.

Step 3

In this step, the isocitrate molecule is oxidized by a NAD molecule.  The NAD molecule is reduced by the hydrogen atom and the hydroxyl group. The NAD binds with a hydrogen atom and carries off the other hydrogen atom leaving a carbonyl group. This structure is very unstable, so a molecule of CO₂ is released creating alpha-ketoglutarate.

Step 4

In this step, CoA, returns to oxidize the alpha-ketoglutarate molecule.  A molecule of NAD is reduced again to form NADH and leaves with another hydrogen.  This instability causes a carbonyl group to be released as carbon dioxide and a thioester bond is formed in its place between the former alpha-ketoglutarate and CoA to create a molecule of succinyl-CoA complex.

Step 5

A water molecule sheds its hydrogen atoms to CoA. Then, a free-floating phosphate group displaces CoA and forms a bond with the succinyl complex. The phosphate is then transferred to a molecule of GDP to produce an energy molecule of GTP. It leaves behind a molecule of succinate.

Step 6

Succinate is oxidized by a molecule of FAD. The FAD removes two hydrogen atoms from the succinate and forces a double bond to form between the two carbon atoms, thus creating fumarate.

Step 7

An enzyme adds water to the fumarate molecule to form malate. The malate is created by adding one hydrogen atom to a carbon atom and then adding a hydroxyl group to a carbon next to a terminal carbonyl group.

Step 8

In this final step, the malate molecule is oxidized by a NAD molecule. The carbon that carried the hydroxyl group is now converted into a carbonyl group. The end product is oxaloacetate which then combines with acetyl-CoA and begin the Krebs cycle all over again.

 

Word Search Puzzle On Enzymes

Multiple Choice On Cells And Carbohydrates

Multiple Choice Questions for Cells and Carbohydrates:
Select the correct multiple answer using ONE of the keys A, B, C, D or E as follows:
A. 1, 2 and 3 are correct
B. 1 and 3 are correct
C. 2, 3 and 4 are correct
D. only 4 is correct
E. all are correct

1) Which of the following statements is true for Prokaryotes?
1. Single-celled organism
2. Lack nuclei
3. Circular DNA
4. DNA in the form of linear chromosomes

2) The polymers whose subunits are monosaccharides are
1. Lactose
2. Cellulose
3. Starch
4. Glycogen

3) The main storage polysaccharides include
1. Starches
2. Maltose
3. Glycogen
4. Lactose

4) Carbohydrate metabolism includes:
1. Glycolysis
2. Pentose Phosphate Pathway
3. Glucaneogenesis and Glycogen Synthesis and Catabolism
4. All of the above

5) What is the role of the Golgi Apparatus?
1. Supply amino acids for fresh protein synthesis
2. Remove excess enzymes
3. Site of protein synthesis
4. Modify, sort, and package proteins and other materials from the endoplasmic reticulum for storage

Multiple Choice Questions On Glycolysis

Multiple Choice Questions for Glycolysis

1) The second priming reaction in glycolysis is catalyzed by which enzyme?
a. Phosphohexose Isomerase
b. Aldolase
c. Pyruvate Kinase
d. Phosphofructokinase-1
e. Glyceraldehyde 3-Phosphate Dehydrogenase

2) When pyruvate is converted to Acetyl-CoA, the enzyme which catalyzes this reaction is
a. Hexokinase
b. Pyruvate Kinase
c. Phosphoglycerate Kinase
d. Phosphofructokinase-1
e. Pyruvate Dehydrogenase Complex

3) The enzyme which is responsible for the splitting of glucose molecules in glycolysis is
a. Hexokinase
b. Aldolase
c. Enolase
d. Phosphoglycerate Mutase
e. Phosphohexose Isomerase

4) When Dihydroxyacetone Phosphate is converted to Glyceraldehyde 3-Phosphate, the reaction is catalyzed by
a. Enolase
b. Phosphoglycerate Mutase
c. Triose Phosphate Isomerase
d. Glyceraldehyde 3-Phosphate Dehydrogenase
e. Pyruvate Kinase

5) Which reaction is considered the most energetically favorable reaction in glycolysis?
a. PEP converted to Pyruvate, catalyzed by Pyruvate Kinase
b. 2-Phosphoglycerate converted to PEP, catalyzed by Enolase
c. Fructose 1,6 Bisphosphate converted to G3P and DHAP, catalyzed by Aldolase
d. Glucose to Glucose 6-Phosphate, catalyzed by Hexokinase
e. G3P to 1,3 BPG, catalyzed by Glyceraldehyde 3-Phosphate Dehydrogenase

Electron Transport Chain

The Krebs’ cycle produces 1 molecule of ATP, 4 pairs of H atoms and 2 molecules of CO2 for every molecule of Acetyl-CoA oxidised. The sequence of reactions in the Electron Transport Chain is as follows:

1. The H donor of NADH2 passes the H to another acceptor, FAD (becomes FADH2).

2. The H atoms are now split into electrons and protons.
3. FADH2 transfers the electrons to the next acceptors called cytochromes (Iron[Fe] containing chromoproteins). The more important is being cytochrome A,B,C and cytochrome oxidase.
4. Electrons from H are first transferred to cytochrome B and this is changed from its oxidised form to the reduced form.
5. Reduced cytochromes then pass their electrons to cytochrome oxidase. Finally, reduced cytochrome oxidase transfers the electrons back to the protons and the H so formed reduced oxygen to water.

   
   

Glycolysis Wordle

For a better view, click the picture.