TCA cycle

After glycolysis has occurred  once oxygen is available, Acetyl-CoA is produced and it enters the Krb’s or TCA cycle which takes place in the matrix of the mitochondria. TCA cycle is easily explained in the form of a diagram:

tca themedicalbiochemistrypage.org

 

The following videos are also very useful!

http://www.youtube.com/watch?v=9EFRHRXPDWo

http://www.youtube.com/watch?v=juM2ROSLWfw

http://www.youtube.com/watch?v=WXHpTHb1MQM

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Kreb’s/ TCA Cycle Video Review

As i previously mentioned, I usually watch a few youtube channels when studying, as it often makes learning fun and easy. Another one of my favourite channels is ThinkWell, who also has a website with a lot of great information on biology and chemistry topics. I came across one of his videos on TCA and will now do a review on it:

http://www.youtube.com/watch?v=9EFRHRXPDWo

Summary of the video:

The video basically breaks down TCA step by step, showing and explaining the mechanisms of each reaction, and ending with the first reactant being the last product, hence emphasizing the cyclic part of the Kreb’s Cycle.

  • His animated voice as well as excessive hand gestures kept the video interesting as well as full attention throughout the entire video.
  • Every single reaction of TCA is explained individually and in depth with mentions including but not limited to: reactions, reactants,  chemical structure of products and reactants, enzymes and by-products.
  • Cutting of compounds showed the physical breaking and forming of bonds example S-CoA.
  • The type of each reaction occurring is mentioned which included but is not limited to: oxidation, NAD reduction, destabilisation, exothermic reactions and subtrate-level phosphorylation.
  • The way in which each reaction occurs and products formed is demonstrated.
  • A downloadable paper to follow along with the video is available on the channel’s offical website: http://www.thinkwell.com

However, one way in which the video can be improved is if a white board is used instead of so many paper so that paper can be saved.

In conclusion, i believe that the video is amazing, makes learning fun and easy while at the same time covering the necessary information.

goodbye (1) www.tangrammedia.com

 

Enzyme video reveiwed

While cramming for subjects, i usually use a couple youtube channels that has concise information about topics. One of my favourite channel is BrightStorm2 which has a range of topics in biology,chemistry,physics and math. The following is a video from their channel on Enzymes:

http://www.youtube.com/watch?v=870MWm0peRI

Summary of the video:

The lecturer talked about enzymes being a protein catalyst, having a substrate specific active site, induced fit theory, and the effect of pH and temperature.

  • Firstly, i thought that the video was concise, but filled with enough information to give you a general idea of Enzymes.
  • His animated voice kept your attention throughout the entire video.
  • The use of a diagram of an Energy vs Time graph on the white board gave you a visual understanding of how enzymes work as a catalyst and lowers activation energy and speeds up the rate of reaction.
  • The use of main points on the white board also gave a visual of the main characteristic of Enzymes that should be known. these main points were also discussed in the video: Protein catalyst, active site, specific to substrate, induced fit theory, pH and temperature.
  • The use of the scissors gave a real life application and therefore better understanding of enzymes being a catalyst and the active site being substrate specific.
  • The use of assistant Laura also gave the video an added touch of familiarity and proved that enzymes act as catalyst and make reactions easier to occur.
  • Diagram of induced fit theory gave a visual, hence better understanding of how the theory works.

 

However, the video can be improved in multiple ways:

  • The video could have been edited so that Laura ripped the paper correctly the first time, proving that enzymes make reactions occur easier.
  • Other topics such as Inhibition, Nomenclature, Enzyme classes, Inorganic catalyst vs biological catalyst, M-M equation, Line-weaver Burk plot and Allosteric enzymes could have been covered. This could have given the video a sense of depth instead of a general idea. In this way, students at university level would find the video very useful.
  • Other graphs such as pH and temperature graphs could have been used.
  • pH and temperature effect on enzymes could have been explained more, instead of simply mentioned.

 

In conclusion, i believe the video is best for cramming purposes, because it give a general sense of Enzymes and their characteristics.

goodbye www.maurilioamorim.com

Is Methylene Blue a cure for a disease? [Published paper #2]

Source: http://www.scientificamerican.com/article.cfm?id=common-lab-dye-found-to-i

So there I was browsing through scientific websites looking for a topic to do my assignment on, and I came across a chemical that I’ve used in biology and chemistry labs before, and apparently it has properties that help in Huntington’s Disease.  This is being researched by Leslie Thompson, a neurobiologist at University of California–Irvine and her team. Leslie Thompson is in the picture below:

Imagehttp://faculty.uci.edu/profile.cfm?faculty_id=4708

Huntington’s disease (HD) is a genetic disorder that disturbs muscle coordination and results in mental deterioration and psychiatric issues. It is usually recognizable in adults in their 30s and 40s. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea. Huntington’s disease occurs when the C-A-G sequence of DNA base pairs repeats too often on the HTT gene, creating a long version of the Huntington protein, which therefore folds incorrectly and produces clumps in the brain. HTT is a protein that interacts with many other proteins as well as has many biological functions. HD is not caused by inadequate production of HTT, but by an accumulation of the toxic function mHTT. It is a neurodegenerative disease, which causes a gradual loss of structure or function or death of neurons.

Imagefolding.stanford.edu

Below is a microscope image of a neuron with inclusion (stained orange) caused by HD, image width 250 µm:

Imagehttp://en.wikipedia.org/wiki/Huntington’s_disease

Methylene blue is said to disrupt the formation of mHTT protein clumps in HD. Methylene blue was used to treat ailments from cyanide poisoning to malaria from since 1897. However, Food and Drug administration has never officially acknowledged it as a therapy for any diseases or illness. There is currently no drug produced to stop HD progression. Methylene blue itself is not harmful to humans.

The research team is currently experimenting with flies and mice. Drosophila flies with mHtt gene were given food mixed with methylene blue for seven days. Results of the flies’ brains showed that protein clumps had been reduced by 87 percent compared with a control group. The mice with the mHTT gene were tested for mobility. The 2-month old treated mice demonstrated irregular clasping of their hind claws only 20 percent of the time in a reflex test, while the untreated mice clasped at a 60 percent rate. Less clasping meant healthier mice. However, the amount of mice used was not large enough to give statistically feasible results and the difference in the tests “dropped off” after 9 weeks.

Imagehight3ch.com

The research team says a lot more research on methylene blue is needed but they are hopeful because the early steps of clumping of the mHTT protein is significantly altered in test tubes, the flies and also the mice. They state that methylene blue may prevent mHTT from sticking to itself. Thompson highlights that “Methylene blue would absolutely require further testing in mouse models and would need safety and efficacy trial before it could be used for humans.”

Now think about the difference that a chemical we use as a stain and indicator..has the ability to save the millions of people that suffer from HD worldwide. Furthermore, what other chemicals purposes are being underrated and not utilized? I really hope that the clinical trials go well and methylene blue is approved as a therapy for Huntington’s Disease.

Imageblogs.nature.com

On curing HIV..[Published Paper #1]

Published Paper Source: http://www.scientificamerican.com/article.cfm?id=new-protein-blocks-hiv

A team of researchers (led by Peter S. Kim) of the Whitehead Institute for Biomedical Research has discovered a protein that can block HIV.

Image

The protein is 5-Helix and it blocks HIV entry into the body when it binds to a region of the HIV protein coat known as gp41 and therefore act as an entry inhibitor. To understand what this means, you must first understand how HIV enters into a human cell. This is done in 5 steps:

  • Binding of HIV surface protein gp120 to CD4 receptor.
  • A conformational change in gp120 increases its affinity for a co-receptor and exposes gp41
  • Binding of gp120 to co-receptor CCR5 or CXCR4
  • Penetration of the cell membrane by gp41. This approximates the membrane of HIV and T cell and promotes their fusion.
  • Entry of the viral core into the cell.

Image

Protein 5-Helix therefore prevents step 4, and gp41 does not penetrate the cell membrane when they bind together. Step 5 is avoided by consequence and the viral core is prevented from entering into the human cell.

HIV is always mutating, it never becomes fixed and 5-Helix also seems to successfully prevent a wide range of HIV strains and hence would be useful in creating a new class of anti-HIV drugs. 5-Helix may even help in fighting other viruses like Ebola, human respiratory syncytial virus (HRSV) and influenza all of which show similar characteristics to HIV.

On the other hand, 5-Helix can be used as preventative treatment or a vaccine.

T-20 is another entry inhibitor that also may have had the same effect as 5-Helix but it was required in large amounts to give a positive result while 5-helix gave the positive result in little amounts.

5-helix inhibits HIV in cell culture.The research team is now determining if 5-helix works in animal models so that they can develop it for humans.

I found this article to be particularly interesting because of the recent developments in HIV which includes a baby and 14 people that were ‘functionally cured’ of HIV. This story can be found in the following article:

http://www.newscientist.com/article/dn23276-more-hiv-cured-first-a-baby-now-14-adults.html

References for pictures:

www.avert.org

blogs.delawareonline.com

Glycolysis Quiz

Its quiz time once again..so put on your thinking caps and make me proud biochemists!

blog26

1) What is the most regulated enzyme?

a)      Adolase

b)      Phosphofructokinase-1

c)       Phosphohexoseisomerase

d)      Enolase

e)      Pyruvate Kinase

2) What co-factor is needed for the conversion of Pyruvate to Acetyl-CoA?

a)      Mg2+

b)      TPP

c)       Cu2+

d)      Vitamin C

e)      All the above

3) What is the co-factor that all kinase enzyme require?

a)      Fe2+

b)      Cu2+

c)       Vitamin A

d)      TPP

e)      Mg2+

4) Which reaction is the only oxidation phase in glycolysis?

a)      Fructose-6-phosphate to Fructose-1,6-bisphosphate

b)      1,3-BPG to 3-Phosphoglycerate

c)       G3P to 1,3-BPG

d)      Phosphoenolpyruvate to Pyruvate

e)      Glucose to Glucose-6-Phosphate

5) In which reactions are ATP produced?

a)      1st and 10th reactions

b)      All reactions of the Energy Generation phase

c)       7th and 10th reactions

d)      Reactions vary according to cell

e)      ATP is produced in the Citric cycle and consumed in Glycolysis

6) In which reactions are ATP consumed?

a)      1st and 3rd reactions

b)      All reactions of the Energy Investment Phase

c)       2nd and 5th reactions

d)      ATP is only produced not consumed

e)      Glucose to Glucose-6-phosphate ONLY

7) Where does glycolysis occur in the cell?

a)      Cytosol

b)      Cytoplasm

c)       Mitochondria

d)      Nucleus

e)      Directly outside the cell

8) Multiple Answer MCQ:

Select the correct multiple choice answer using ONE of the keys A,B,C,D or E below:

a)      1 and 4 are correct

b)      2 and 3 are correct

c)       Only 4 is correct

d)      1 and 3 and 4 are correct

e)      2 and 4 are correct

8) Which reactions are irreversible?

1)      Glucose-6-Phosphate to Fructose-6-Phosphate

2)      Glucose to Glucose-6-phosphate

3)      DHAP to G3P

4)      Phosphoenolpyruvate to Pyruvate

9) Why is/are this/these reaction(s) irreversible?

a)      Backward reaction is not energetically feasible

b)      Not enough product is made for a reverse reaction

c)       Backward reaction produces too much heat

d)      Change in structure of product prevents reactants from being made.

e)      All of the above

10) What enzyme is used to convert Glucose-6-Phosphate to Fructose-6-Phosphate?

a)      Aldolase

b)      Enolase

c)       Phosphohexose isomerase

d)      Phosphofructokinase-1

e)      Glucose-6-Phosphase

11) What is the by-product when Enolase converts Phosphoglycerate to Phosphoenolpyruvate?

a)      NADH

b)      H2O

c)       ATP

d)      DHAP

e)      TPP

12) What happens to pyruvate when oxygen is unavailable?

a)      It is converted to L-Lactate

b)      It is converted to Ethanol and enters Citric cycle

c)       It is converted to Acetaldehyde and enters Citric cycle

d)      It is converted to Acetyl-CoA and enters Citric cycle

e)      All the reactions of Glycolysis are reversed

FML ))):

So last week..i had a chem exam that i knew nothing for..and i came up with what i thought was a genius idea! I decided to all-night monday into tuesday, and tuesday into wednesday to study chemistry. Monday’s all-nighter went great but i began to feel sick in the morning because caffeine makes me feel sick, and i missed the biochem lecture.

blog20

So..i was like no scene..i’ll just all-night in school tuesday and go straight into biochem lecture wednesday morning. But OFC 6am i’m running 48hrs withour sleep…dying..thinking 3 more hours to biochem lecture is more than infinity hours and i leave school at 7am. Then to find out we had two exams each day! And also TCA which was taught in class is the only topic with NO podcasts!

blog28

blog2

 

Great. FML. I’ll have to do my own research to be able to blog this week. WEHH Happy easter to me 😦

Glycolysis…this is friggen awesomeeeeee

gly5

Stop whatever you are doing and watch this AMAZING video!!!

Now tell me that song isnt stuck in your head and you’ve already learnt and memorized BOTH glycolysis and TCA!!!

Regardless of that vid, in case you’re not a huge rap fan..allow me to break it down for you!

Glycolysis is the process that breaks down Glucose into Pyruvate and produces ATP along the way. ATP is used for energy. ATP is like money to cells, if you aint got no ATP, you aint got no game. And guess what? Glycolysis is going on in your body RIGHT NOW! As you read this, 10 different enzymes are working hard to convert that sandwich you ate into pyruvate. How you ask? This picture should give you a good explanation:

gly2

In the first reaction, glucose is converted to glucos-6-phosphate because the phosphate group makes it more reactive as well as prevents it from passing through the glucose transporter.

All kinases enzyme require Mg2+ as a cofactor. All these enzymes are induced-fit.

Also, wherever a Kinase is involved, ATP is either being broken or formed.

The enzyme in the third reaction; Phosphofructokinase-1 is the most regulated enzyme, and the this reaction is also the second priming reaction.

The sixth reaction is the only oxidation reaction in glycolysis by the enzyme Glyceraldehyde-3-phosphate dehydrogenase, and hence forth, 2molecules of everything is produced in each reaction.

There are 3 irreversible reactions in glycolysis and this is because the forward reaction has a high negative deltaG value and hence a high positive deltaG value will be needed to overcome for a backward reaction to occur.

The 3 irreversible reactions are:

1st reaction: Glucose –> Glucose-6-phosphate

3rd reaction: Fructose-6-phosphate –> Fructose-1,6-bisphosphate

10th reaction: Phosphoenolpyruvate (2) –> Pyruvate (2)

The 2 enzymes involved in sub-level-phosphorylation are;  Phosphoglycerate kinase and Pyruvate kinase.

Fate Of Pyruvate:

After pyruvate has been made, 3 things can happen depending on if oxygen is available or not.

If oxygen is available:  Pyruvate is converted to Acetyl-CoA by enzyme Pyruvate dehydrogenase complex and NADH is produced as a by-product. Acetyl-CoA then enters the TCA cycle.

If oxygen is unavailable:

Pyruvate is converted to L-Lactate by the enzyme Lactate dehydrogenase and NAD+ is produced as a byproduct.

Fermentation can also occur: Pyruvate is converted to Acetaldehyde which is then converted to Ethanol by enzyme Pyruvate decarboxylase and alcohol dehydrogenase respectively. For the enzyme Pyruvate decarboxylase; co-factors include Mg2+ and TPP (thiamine pyrophosphate) and CO2 is produced as a by product. Conversion of Acetaldehyde to ethanol produces NAD+ as a by-product.

 

And that folks, is Glycolysis! Hope you learnt a thing or two! catch ya next time.