ORLISTAT- To Be Or Not To Be THE MAGIC DIETARY PILL

           ORLISTAT

by: Jiwani Peters

Orlistat is a novel dietary supplement that has been hot on the market as it is a unique anti-obesity (weight-loss) drug. It is known by two names on the market:

1. Alli – the over-the-counter version : 60 mg

alli

2. Beacita – the over-the-counter version : 60 mg

beac

3. Xenical – the doctor prescribed version : 120 mg *** the more potent version

xeni

The manufacturers, Roche Pharmaceutical Company, claim a result of  30% decrease in fat absorption from exogenous fat sources i.e. the diet, hence weight loss. The key ingredient tetrahydrolipstatin is a derivative of lipostatin which inhibits gastic and pancreatic lipases. However because the Orlistat has the derivative; Tetrahydrolipstatin (THL), it selectively targets the action of pancreatic lipase and inhibits it. So it would interfere with dietary fat absorption, enhance weight loss and weight maintenance.

Tetrahydrolipstatin also has no adverse psycological effects such as addiction or dependence on it unlike other Amphetamines. Nor does this ingredient cause damage to the body (strokes, etc). This is because Tetrahydrolipstatin expresses itself externally in gastrointestinal tract only and Orlistat is lipophilic (water hating) so as such only less than 1% is absorbed into the blood stream which is 70% water i.e. mostly water.

Orlistat specifically targets and inhibits the action pancreatic lipase which is the main degradative lipase in lipid metabolism of long-chain fatty acids entering the digestive tract.

–     Pancreatic Lipase

panc lipase

Pancreatic Lipase is made in the pancreas and secreted by it and goes into the small intestine, where it hydrolyses the ester bonds at Carbon 1 and Carbon 3 on the Triacylglyceride (TAG) molecule resulting in a mixture of 2-monoacylglycerol + fatty acids (which can be absorbed by the capillaries = weight gain)

tag hydrolysis

Chemical equation: Triacylglycerol + 2 H2O   2-monoacylglycerol + 2 fatty acid anions

So by Orlistat selectively targeting and potently inhibiting this enzyme (90% action is stopped), it directly stops the hydrolysis and absorption of the fat by the body. Orlistat also inhibits gastric lipase, carboxylester lipase, and phospholipase A2 that helps in lipid digestion but advantageously has no effect on the activity  trypsin, chymotrypsin, amylase (enzymes involved in protein digestion) and phospholipases.

  •  Orlistat’s Mechanism of Action

orlistat

Orlistat binds covalently close to or at the active of pancreatic lipase. This new stable pancreatic lipase + inhibitor complex causes a conformational change which distorts the active site so it is exposed. Upon exposure, THL binds to the hydroxyl group on the Serine 152 residue at the active site of the lipase, as an ester bond. This obstructs the catalytic power of the lipase making it ineffective to do its hydrolyzing job.

So the dietary fats pass through the gastrointestinal tract without degradation and are excreted in the feces, so the feces is now of an oily nature; Steatorrhea.

  • Overall EFFECTS
  1. Orlistat decreases lipids digestion and hence absorption. However Orlistat still needs to be used alongside a proper exercise regimen and a low-calorie diet. Because it is dependent on stopping absorption relative to the amount of fat ingested. Higher amounts of fat means that 30% of that amount will not be digested so the fat absorbed increase with increased fat intake.
  1. Orlistat improves insulin sensitivity, attributed to the reduction of free fatty acids (no obesity) so insulin clearance increases in activity and decreases hepatic glucose production. (Obesity is linked to diabetes). Studies have also shown that with long term Orlistat treatment, cholesterol levels and LDL cholesterol levels reduce, as fat from the diet would be present to be packaged into chylomicrons to be transported and deposited to the cells around the body.
  1. Orlistat has no drug-drug interaction with most of obesity drugs such as antihypertension, antidiabetics and cadiotonic medications. Nor does it have any interaction with lipid soluble vitamins or ß-carotene or serum hormones such as insulin, thyroxine and catecholamines. Orlistat seems to have no drug toxicity thus making it so revoluntary.
  1. Side effects:

–           Include several mild gastrointestinal adverse effects:  oily spotting, flatulence, and frequent loose stools.

–           Vitamin D and β-carotene levels decreas (but remain within the normal range).

–           The concentration of high-density lipoprotein (HDL) was also decreases.

References:

http://faculty.ksu.edu.sa/Alomar/Full%20Text%20Articles/287-RJAS.pdf

http://www.ncbi.nlm.nih.gov/pubmed/1899234

http://www.jnutbio.com/article/S0955-2863(98)00006-0/abstract

http://www.researchgate.net/publication/21610194_Identification_of_the_active-site_serine_in_human_pancreatic_lipase_by_chemical_modification_with_tetrahydrolipstatin

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The “coolonomics” of Science – Metabolomics

The metabolome is the full complement of metabolites within a cell at any point in time. The metabolome is dynamic as small molecules are undergoing many different processes such as absorption, synthesis, and degradation. The unique and dynamic nature of the metabolites allows one to analyze the physiology of a cell and therefore be able to understand its biochemical and regulatory mechanisms.
Metabolomics is non invasive and its is directly linked to phenotype. It’s non invasive nature makes it a safe method of investigation when it is used in understanding diseases in the human body, and its direct link to phenotype along with the information on genotype in the metabolic profile will one day allow courses of treatment to be tailored to specific cases leading to swift and effective treatment.
Metabolomics is already important to bio marker discovery. In metabolomics, metabolites act as bio markers which can be used to differentiate between a disease and a control group. If a metabolite is present in a disease group, but not the control group it is then classified as the bio marker. When this biomarker is identified and its physiology examined, the way a disease acts on a cell can be determined and a mode of treatment can then be decided on.
An example of this is the use metabolomics to investigate the possible mechanisms of obesity. Metabolomics uses nuclear magnetic resonance spectroscopy or mass spectroscopy of biological sample to understand how they work under different conditions. This allows metabolomics to tell us what is happening in a biological system by following the actions of the metabolites. Obesity is a disease that is directly related to metabolic changes, the ability of metabolomics to detect even slight changes in metabolic function inevitably increases our knowledge of obesity and diseases like it, and how it can be cured or prevented.
For the future there seems to be great promise in developing personalized medicine, through metabolomics. Currently, classical methods in biochemistry are used to determine individual concentrations of metabolites to determine diseases. Using metabolomics, we will be able to make medical diagnosis’ quicker and earlier due to the potential of metabolomics to identify hundreds of metabolites rapidly.

References :
http://www.news-medical.net/news/2006/10/24/20736.aspx
http://www.hindawi.com/journals/bmri/2013/792527/
http://www.ebi.ac.uk/training/online/course/introduction-metabolomics/importance-metabolomics/some-applications-metabolomics
http://www.hindawi.com/journals/bmri/2012/805683/

You can’t fool me, I’m a Biochemican !

So back in Jamaica, I was an athlete throughout prep AND high school. If you know anything about Jamaica, you must know that we take our Track and Field VERY seriously, more so when you reach to the high school level. I was a long jumper, you know those crazy people who are willingly propel themselves high in the air and launch themselves at sand or dirt they like to pretend is sand,well you need super strong legs to do that. So in high school I started doing something I thought i would never do, I started pumping iron (weight lifting), and although I feared I’d start to look too masculine my coach didn’t think I was gaining enough muscle mass. CUE THE SUPPLEMENTS !
My coach bought it in chocolate flavor, and I accepted it with the same vigor I would exude when taking a nice cup of Milo from my granny. One word. YUCK. I tried to avoid supplements at all costs after that, it got so bad that my coach used to sit me in his office chair until I drank it all. But now a few years later, on the UWI campus here in Trinidad, Protein Hut has me thinking I could actually have protein everyday. I mean it doesn’t taste like a mcflurry, but I don’t have the urge to spit it out or rip my tongue from my throat. 
This brings me to the point of this blog post, is it worth the money? Since doing Mr. Matthew’s course this semester ( HOLLA AT MY BIOL 2360 CLASS !), I find myself really looking at the ingredients and wondering if a supplement can do what is says or will I just be passing money out my bum, LITERALLY! I’m totally loving the MusclePharm brand, which is what the folks at protein hut use, and today I’ll be examining their carnitine core supplement.
467x600_CarnitineCore-copy

The bottle says its a “balanced carnitine formula with raspberry ketones” that; “helps reduce body fat*”, “helps athletic performance and endurance*” and “helps convert fat to energy*”. I don’t know what these asterisks stand for, but if I were to guess…

Anywhoo, where do we get carnitine and ketones from? According to the National Institutes of Health, the average healthy human produces enough daily carnitine from lysine and methionine in the liver and kidneys, and carnitine can also be supplied from Animal products, a higher content of it being in red meats. Ketone bodies are produced from fatty acids in the liver when the body is in the fasting state, and an alternate source of energy is needed due to depleted sources of glucose.

How does carnitine work?
In the mitochondrial matrix, long chain fatty acids are broken down through a process called beta oxidation, the products of beta oxidation are Acetyl CoA, FADH2, NADH and H+. The Acetyl CoA enters the citric acid cycle which results in usable energy in the form of ATP being produced. The FADH2, NADH and H+ undergo oxidation in the mitochondrial electron transport system, which also yields ATP.
However, there is one problem, The long chain fatty acids cannot breech the mitochondrial membrane for beta oxidation to occur ! Carnitine acyltransferase I which can be found on the outer membrane of the mitochondria transfers the fatty acyl from fatty acyl CoA to the OH group of carnitine. The acyl-carnitine formed is able to pass the outer membrane on the mitochondria and travel acroos the intermembrane space to a translocase enzyme thats carries the acyl carnitine to carnitine acyltransferase II, which the exchanges the carnitine for CoA.

Ketones
The synthesis of ketones occurs in relation to level of glucose in the blood. If the level of glucose in the blood is low, ketones are synthesized for use as a secondary source of energy.

So does carnitine core by MusclePharm do what it says it can?

1. “helps reduce body fat*”
 Carnitine plays an important role in transporting long fatty acid chains into the mitochondrial matrix to be broken down. If the rate of fat breakdown can be increased by supplying the body with carnitine to increase the rate at which fatty acid chains enter the mitochondria,body fat can indeed be reduced.

2.”helps athletic performance and endurance*”
Examining the role of carnitine in the body, it obvious that carnitine plays a very important role in supplying energy to the body. By supplying the body with more carnitine, fatty acids can be transferred to the mitochondrial matrix more quickly, thus producing more energy at a more rapid pace.
Furthermore, by supplying the body with ketones, this supplement ensures that when all the glucose in the body is used up the body of the athlete in question can use it as a secondary source of energy.

3.”helps convert fat to energy*”
This one is just a little DUH ! We already saw that once carnitine helps those long fatty acid guys into the mitochondrial matrix, they undergo beta oxidation. The products of beta oxidation proceed to enter to energy forming pathways. More carnitine, the more fat turned to energy.

Now, I’m going to venture to guess why our little friend the asterisk is beside all these claims. As stated by the National institutes of health the body produces enough carnitine for the average healthy adult, and ingesting this product wont see the fat on the average person disappearing just so ! I don’t consider weight lifters, olympians, bikini fitness models or anyone who exercises on a daily basis to be your average healthy adult, (Seriously, the average person doesn’t do any form of planned exersise) and this supplement will more than likely do these things for them to a certain extent. I say to a certain extent, because there is a point at which the body can use only so much carnitine !

Well carnival is only 3 months away, and I’m looking at that little bit of costume and so much of me to fit in it. I will definitely be giving carnitine core a try, and of course I’m gonna go beast in the gym !
WISH ME LUCK ! 

Farewell….

Hi Guys,

Well we’ve come to the end of this blog series. And we hope that with all of the posts, videos, prezis, puzzles, etc that we were able to impart some knowledge to you AND to also show how FUN Biochemistry can be!!

So to all, we say Farewell 😦

….for now :p

 

Love from Trinidad and Tobago, Jamaica and St. Vincent and the Grenadines!!

xxx- Wani 🙂

 

P.S. – For even more fun and even more indepth information concenring everything that is Biochemistry, go to…..

https://www.youtube.com/channel/UCiObLTmsNXhQao_VFrvBZFQ – Our awesome lecturer’s youtube channel! BiochemJM.

Become a Biochemian today.

 

kk

 

 

 

 

WHAT IS DNA??

DNA stands for DeOxyRiboNucleic Acid

Reference: http://www.youtube.com/watch?v=q6PP-C4udkA

 

It is thought that DNA evolved from when 2 RNAs (one strand messenger) wrapped around each other to form DNA (double strand)

The backbone of DNA composes of: deoxyribose sugar + phosphate

In the nucleotide, the sugar has 5 carbons: 1’, 2’, 3’, 4’, 5’   * ‘ – means prime

Each strand has a 3’ end and a 5’ end. The two strands run anti-parallel to each other. So the 3’ end of one strand is bonded to the 5’ end of the other stand.

Nucleotides are only added onto the 3’ ends!!!!

DNA is made up of covalent and hydrogen bonds. Covalent (strong) bonds are found between nucleotides above and below each other, Hydrogen bonds between nucleotides across from each other. The hydrogen bonds are important so they can be easily broken when DNA replication has to take place. The covalent bonds prevent the helix from falling apart completely.

 

dna part

NUCLEIC ACIDS :)

There are four main macro-molecule groups all biological molecules fit into:

  1. Nucleic Acids make up 25% composition of the body)
  2. Carbohydrates make up  15% composition of the body)
  3. Proteins make up 50% composition of the body)
  4. Lipids make up 10% composition of the body)

The table below shows the monomers that make up these macro-molecules.

macromolecules

 

 

 

Another look can be

01p16kga

 

 

WE ARE GOING TO PAY ATTENTION TO NUCLEIC ACIDS!!

Reference: http://www.youtube.com/watch?v=NNASRkIU5Fw

There are many Nucleic Acids such as: Deoxyribonucleic acid (DNA), Ribonucleic acid (RNA), Messenger RNA (mRNA), Transfer RNA (tRNA), Mitochondria DNA (mtDNA)

However the two main ones are DNA and RNA which are the genetic materials of all life and are very important in the making of proteins as the Central Dogma illustrates:

a.

550px-Extended_Central_Dogma_with_Enzymes

 

 

                                                b.

 

cdog

 

This video further explains the Central Dogma so CLICK! CLICK! CLICK!

3D Animation of DNA to RNA to Protein

 

NUCLEIC ACIDS

– Nucleic acids are found in nucleus, mitochondria, and chloroplasts, cells with no nucleus (bacteria and viruses)
– Nucleic acids make proteins in ribosomes
– Nucleic acids make genes for heredity
– Nucleic acids compounds are made up of only carbon, nitrogen, oxygen, hydrogen and phosphate (no sulphur)
– Nucleic acids are made up of nucleotides.

typical nuc

 

 

Nucleotides have 3 parts:

 

1. Phosphate groups
2. Pentose sugar- 5 carbon
*NB – for Deoxyribose (DNA) the pentose sugar is missing oxygen on hydroxyl group as opposed to Ribose (RNA)
3. Nitrogenous base (made up of nitrogen) – also known as nucleobases
*NB – They are different for each nucleotide. It can be a combination of 4 out of these 5 base pairs: Guanine, Cytosine, Adenine, Thymine or Uracil.

dna_rna1

 

 

The base pairs of nucleic acids can range from 3 to millions
– In DNA, the four nucleobases are – Guanine, Cytosine, Adenine, Thymine
– In RNA, the four nucleobases are – Guanine, Cytosine, Adenine, Uracil
These Nucleobases are placed into two major groups which is dependent on size:

1. Purines – these have 2 rings and are bigger: Adeneine and Guanine

2. Pyrimidines – these have 1 ring and are smaller: Cytosine, Thymine and Uracil

There a 4 different nucleotides ATP,GTP (purines) TTP,CTP

 

These bases have to bond to form the base pairs. They have 2 ways to bond:

  1. When they come into contact with each other, and are above and below like Adenine and Guanine, they lose water through Dehydration and form a Covalent bond.

–> RNA: number of nucleotides in a row connected by a covalent bond

  1. When two nucleotides contact, like Adenine and Thymine, one is flipped so it bonds horizontally and forms Hydrogen bonds(oxygen and hydrogen interaction)

: Adenine and Thymine (2 Hydrogen bonds)

: Guanine and Cytosine (3 Hydrogen bonds)

bonding

 

DNA is more stable than RNA due to

  1. A lot of hydrogen bonds between 2 adjacent base pairs and compatible base pairs away from each other. E.g. Thymine on 4th base pair connects with Adenine on 6th base pair.

 

  1. Hydrophobic Interactions of the center of the helix

 

* DNA vs RNA

DNA RNA
Has Thymine Has Uracil
Double helix Single helix
Found in the nucleus of the cell Found everywhere in the cell

The picture below shows the RNA single strand and the DNA double helix strand

dna and rna