Biochemistry Den: June 2011

Wednesday, June 8, 2011

Protein folding made easy

Protein folding has nothing to do with laundry. It is, in fact, one of the central questions in biochemistry. Protein folding is the continual and universal process whereby the long, coiled strings of amino acids that make up proteins in all living things fold into more complex three-dimensional structures. By understanding how proteins fold, and what structures they are likely to assume in their final form, researchers are then able to move closer to predicting their function.

This is important because incorrectly folded proteins in humans result in such devastating diseases as Alzheimer's, Parkinson's, Huntington's, emphysema and cystic fibrosis. Developing better modelling techniques for protein folding is crucial to creating more effective pharmaceutical treatments for these and other diseases.

Computational methods of modelling protein folding have existed for a couple of decades. But what McGill researcher Jérôme Waldispühl of the McGill Centre for Bioinformatics has done, working with collaborators from MIT, is to develop algorithms that can work from a laptop computer to examine a protein's fundamental chemical properties and then scan a number of possible protein shapes before predicting the final form that the protein is likely to take.

The results have been impressive. Whereas classical techniques for predicting protein folding pathways required hundreds of thousands of CPU hours to compute the folding dynamics of 40 amino acids proteins, the program tFolder implemented by Solomon Shenker – a former McGill under-graduate student now at Cornell – has been able to predict correctly in 10 minutes on a single laptop, a coarse-grained representation of the folding pathways of a protein with 60 amino acids.

Waldispühl and his students continue to work on their algorithm to improve its success rate at predicting protein folding with broader categories of proteins including some that are important in DNA-binding. The research was recently presented at the 15th Annual International Conference in Research in Computational Molecular Biology (RECOMB 2011).

Heaviest element officially named Copernicium

Label follows tradition of naming elements after merited scientists

The heaviest element yet known is now officially named "Copernicium," after the astronomer Nicolaus Copernicus. Copernicium has the atomic number 112 — this number denotes the number of protons in the nucleus of an atom. It is 277 times heavier than hydrogen, making it the heaviest element officially recognized by international union for chemistry IUPAC.

The name for the element was suggested by the team that discovered it, led by Sigurd Hofmann at the GSI Helmholtzzentrum für Schwerionenforschung in Germany. The suggested name "Copernicium" in honor of Nicolaus Copernicus (1473-1543) follows the tradition of naming chemical elements after merited scientists.

IUPAC officially announced the endorsement of the new element's name on Feb. 19, Nicolaus Copernicus' birthday. Copernicus' work in the field of astronomy is the basis for our modern, heliocentric world view, which states that the sun is the center of our solar system with Earth and all the other planets (in our solar system) circling around it.

On the periodic table of elements, Copernicium will have the symbol "Cn." The team had originally suggested "Cp" as the element's symbol, but because this abbreviation has other uses in science (such as a material's specific heat), the team agreed to "Cn."

Other elements named for famous scientists include: Einsteinium (for Albert Einstein), Fermium (for nuclear physicist Enrico Fermi), and Curium (after Marie Curie and her husband Pierre).

Hofmann and his team were able to produce the element Copernicium at GSI for the first time on Feb. 9, 1996. Using the 100-meter long GSI accelerator (an atom smasher), they fired zinc ions onto a lead foil. The fusion of the atomic nuclei of the two elements produced an atom of the new element 112. But the atom was only stable for a fraction of a second.

Further independent experiments confirmed the discovery of the element. Last year, IUPAC officially recognized the existence of element 112, acknowledged the GSI team’s discovery and invited them to propose a name.

Periodic table gains two elements

Chemistry officials have confirmed the creation of two new elements - so now names will be given to elements 114 and 116.

By John Roach

The periodic table has two new heavyweights, elements 114 and 116, according to a committee of international chemists and physicists. The elements are fleeting — they are created by bombarding lighter elements together and exist for less than a second before undergoing radioactive decay. Such a short lifespan means that we can't say much about them other than they really do exist.

"The lifetimes of these things have to be reasonably long so you can study the chemistry — meaning, pushing a minute," Paul Karol of Carnegie Mellon University in Pittsburgh, who chaired the committee that approved the new elements, told New Scientist.

The evidence for element's existence has been mounting for more than a decade. In 1999, for example, Russian scientists with the Joint Institute for Nuclear Research bombarded plutonium-244 with calcium-48 to produce a single atom of 114, which has an atomic weight of 289.

Further collaboration between Russian and U.S. scientists at the Lawrence Livermore National Laboratory resulted in papers published in 2004 and 2006 on the creation of the elements 114, 116, and the yet-to-be-approved 118.

To create 116, the researchers smashed together curium atoms, which have 96 protons in their nucleui, with calcium nuclei, which have 20 protons. This lasted a few milliseconds before decaying into 114, which in turn decayed into copernicum, element 112.

These papers served as the basis for review by the International Union of Pure and Applied Chemistry, which made the formal announcement of the new elements on June 1 with the publication of a paper in Pure Applied Chemistry.

The elements currently go by the placeholder names ununquadium and unuhexium, which by IUPAC convention are derived from the digits 114 and 116. The Russian discovery team at JINR has proposed flerovium for 114, after Soviet element finder Georgy Flyorov, and muscovium for 116, after Russia's Moscow region, according to Wired.

The committee also reviewed claims associated with elements 113, 115, and 118, but found they are not yet conclusive and thus do not meet the criteria for discovery. For more information on how the elements were discovered and the review process, check out the video above from the University of Nottingham's Periodic Table of Videos series.

Saturday, June 4, 2011

Few Images collections for students

Digital Weighing Machine

Double Beam VIS-UV_Spectrophotometer

Generic HPLC

Thermometer

HPLC

Intelligent High Speed Refrigerated Centrifuge

Thermometer

Modern Stethoscope

PAGE

PCR - Thermo cycler

REFRIGERATED CENTRIFUGE

Sphygmomanometer

Stethoscope

PCR - Thermo cycler

PCR Thermo cycler

PCR

Upper Arm Digital Sphygmomanometer

Auto Blood pressure monitor A386d0

VIS-UV_Spectrophotometer

Biotechnology Colleges in India

Inborn Errors of Metabolism

Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances into others . In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or to the effects of reduced ability to synthesize essential compounds. Inborn errors of metabolism are now often referred to as congenital metabolic diseases or inherited metabolic diseases.

Major categories of inherited metabolic diseases

Disorders of carbohydrate metabolism - glycogen storage disease(Type 1= Von Gierke’s,Type 2- Pompe’s disease)
Disorders of amino acid metabolism - phenylketonuria , maple syrup urine disease, glutaric acidemia type 1
Disorders of organic acid metabolism - alcaptonuria
Disorders of fatty acid oxidation and mitochondrial metabolism
Disorders of porphyrin metabolism - acute intermittent porphyria
Disorders of purine or pyrimidine metabolism - Lesch-Nyhan syndrome
Disorders of steroid metabolism - congenital adrenal hyperplasia
Disorders of mitochondrial function - Kearns-Sayre syndrome
Disorders of peroxisomal function - Zellwegger’s (Cerebro-Hepato-renal) X-linked Adrenoleukodystrophy
Lysosomal storage disorders - Mucopolysaccharidoses (X-linked Hunter’s, Hurler’s),Gaucher disease,Tay-Sachs Disease

PCR Saliva Tests Useful for Congenital CMV Screening

Real-time polymerase-chain-reaction (PCR) assays of saliva samples are accurate for detecting congenital cytomegalovirus infection in newborns, researchers found.

Assays using both liquid and dried saliva had high sensitivity and specificity for identifying the infection, with positive predictive values over 90% and negative predictive values at or near 100%, according to Suresh Boppana, MD, of the University of Alabama at Birmingham, and colleagues.

Unlike the standard rapid cultures of saliva and urine samples, the PCR assays can be automated and adapted for widespread screening, which could identify babies who would benefit from early intervention to mitigate the effects on speech and language development of any cytomegalovirus-related hearing loss, the researchers reported in the June 2 issue of the New England Journal of Medicine.

Although screening would allow for early identification, the standard culture method performed on saliva or urine samples cannot be automated, which limits utility for large-scale screening. Most infants with congenital cytomegalovirus infection are not identified because the infection is asymptomatic and testing is not routine.

A previous study by Boppana's group showed the dried-blood-spot PCR assays identified fewer than 40% of cytomegalovirus-infected newborns, so the researchers compared real-time PCR assays (using either liquid or dry saliva samples) with rapid culture at seven U.S. hospitals.

Of those screened with the liquid-saliva PCR assay, 85 infants (0.5%) were positive on both rapid culture and the PCR assay. Another eight infants were positive on the PCR assay but not on culture. Of the 34,989 screened, 0.5% were positive for cytomegalovirus using at least one of the three screening methods.

Of the newborns screened with the dried-saliva PCR assay, 76 (0.44%) were positive on rapid culture -- 74 of whom were also positive on the PCR assay. Another eight infants were positive on the PCR assay only. The sensitivity and specificity of the PCR assay were 100% and 99.9%, respectively, and the positive and negative predictive values were 91.4% and 100%, respectively.

The sensitivity and specificity of the PCR assay were 97.4% and 99.9%, respectively, and the positive and negative predictive values were 90.2% and 99.9%, respectively.
Of the 16 infants who were positive on one of the PCR assays, but not on rapid culture, 13 underwent follow-up testing of saliva and urine samples; only three actually had a cytomegalovirus infection.

"Although false-positive saliva PCR results could lead to unwarranted parental anxiety and additional testing in infants to confirm or rule out congenital cytomegalovirus infection, the overall frequency of false-positive results for both liquid-saliva and dried-saliva PCR assays was less than 0.03%," they wrote. Those false-positives may have been the result of cytomegalovirus-containing maternal secretions in the infants' mouths, according to the researchers.

"Nevertheless," they added, "when saliva PCR assay is used to screen newborns, a positive screening result should be confirmed within the first three weeks of age to avoid false-positive screening results."

Although the dried-saliva PCR assay failed to identify two infants who had the infection according to the standard rapid culture -- and the liquid-saliva PCR assay did not miss any -- the researchers suggested that using dried saliva may be preferable for screening.

"The simplified procedures for specimen collection, storage, and transport, combined with the high sensitivity, support dried-saliva PCR assay as a reasonable approach to cytomegalovirus screening in newborns," they wrote.

They acknowledged that the study was limited in that the infants who were found negative on initial testing were not enrolled in follow-up testing to confirm the absence of the infection.

Action Points:

Explain that PCR testing of liquid or dried saliva was able to identify newborns with congenital cytomegalovirus infection with high sensitivity and specificity.
Note that congenital cytomegalovirus infection is usually asymptomatic but can cause hearing loss; currently newborns are not screened for this infection.

Thursday, June 2, 2011

Very good Biochemistry book is here for Review

Lippincott's Illustrated Review

Biochemistry

Authors
By Pamela C.

Champe,
Richard A. Harvey,
Denise R. Ferrier

Description: Lippincott's Illustrated Reviews: Biochemistry has been the best-selling medical-level biochemistry review book on the market for the past ten years. The book is beautifully designed and executed, and renders the study of biochemistry enormously appealing to medical students and various allied health students. It has over 125 USMLE-style questions with answers and explanations, as well as over 500 carefully-crafted illustrations. The Third Edition includes end-of-chapter summaries, illustrated case studies, and summaries of key diseases.

About the metabolic fate of the carbon skeleton of amino acids

An amino acid that yields acetoacetyl CoA during the catabolism of its carbon skeleton would be considered:

a) glycogenic

b) ketogenic

c) glycogenic and ketogenic

d) neither glycogenic nor ketogenic

e) essential

f) non essential

Answer is

Answer: (b) Ketogenic (Since the question only make reference to acetoacetyl CoA, we assume that it is the final product of the catabolism of this amino acid and no glucogenic metabolites are produced.)

Amino acids are used for different purposes in our body. Most of the metabolic pool of amino acids is used as building blocks of proteins, and a smaller proportion is used to synthesize specialized nitrogenated molecules as epinephrine and norepinephrine, neurotransmitters and the precursors of purines and pyrimidines.

Since amino acids can not be stored in the body for later use, any amino acid not required for immediate biosynthetic needs is deaminated and the carbon skeleton is used as metabolic fuel (10-20 % in normal conditions) or converted into fatty acids via acetyl CoA.

The main products of the catabolism of the carbon skeleton of the amino acids are pyruvate, oxalacetate, a-ketoglutarate, succinyl CoA, fumarate, acetyl CoA and acetoacetyl CoA.

When carbohydrates are not available (starvation, fasting) -or cannot be used properly, as in diabetes mellitus, amino acids can become a primary source of energy by oxidation of their carbon skeleton, but also by becoming an important source of glucose for those tissues that only can use this sugar as metabolic fuel.

The formation of glucose from amino acids (gluconeogenesis) in liver and kidney is intensified during starvation and this process becomes the most important source of glucose for the brain, RBC and other tissues.

Amino acids in skeletal proteins can be used, in a situation of prolonged starvation as an “emergency” energy store that can yield 25000 kcal.

Amino acids can be classified according to the metabolic fate of the carbon skeleton in:

- ketogenic,

- glucogenic

- ketogenic and glucogenic

Ketogenics: Amino acids that yield acetyl CoA or acetoacetyl CoA ( e.g. they do not produce metabolites that can be converted in glucose).

Lysine and Leucine are the only amino acids that are exclusively ketogenics.

Glucogenic: Amino acids whose catabolism yields to the formation of Pyruvate or Krebs Cycle metabolites, that can be converted in glucose through gluconeogenesis (Remember the pathway: pyruvate-àoxalacetate-à (P) enol pyruvate…etc.).

Glucogenic amino acids are: Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glycine, Histidine, Methionine, Proline, Serine, and Valine

Glucogenic and ketogenic: Amino acids that yield some products that can become glucose and others that yields acetyl CoA or Acetoacetyl CoA.

Amino acids of this kind are Isoleucine, Phenylalanine, Tryptophan, Tyrosine and Threonine.

When Tyrosine becomes an essential amino acid

In patients with PKU, Tyrosine becomes essential, since it is formed from Phenylalanine in the reaction that is impaired in Phenylketonuria.

Additional information:

Most of the textbooks classify amino acids from the nutritional point of view, in two groups: essential or not essential. Essential amino acids are considered those amino acids that can not be synthesized by an organism and so should be consumed in the diet; non essential amino acids are those amino acids that can be synthesized. This classification is not related to the importance of the amino acids, but with the fact of them being required in the diet or not.

According to this classification, the essential amino acids are:

Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine

(Mnemonics: PVT TIM HALL:

Phenylalanine

Valine

Threonine

Tryptophan

Isoleucine

Methionine

Histidine

Arginine

Leucine

Lysine)

Non essential amino acids are:

Alanine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine, Tyrosine

Like most facts in biology, this “black and white” classification is not 100 % accurate. Actually, some amino acids are conditionally essential or partially essential, since some “essential” amino acids, like arginine, can be synthesized by the body. Arginine is synthesized in the urea cycle, for example, but it is considered essential since the quantity of Arginine that is synthesized is not enough during the growing process.

Tyrosine is an amino acid that is synthesized in the body from Phenylalanine, that is an essential amino acid. This reaction is catalyzed by the enzyme Phenylalanine Hydroxylase, that use as cofactor reduced tetrahydobiopterine.

If Phenylalanine is deficient in the diet, then the body requires tyrosine in the diet.

In Phenylketonuria there is an excess of Phenylalanine, since the body can not metabolize it, but Phenylketonuria is a consequence of a deficit of Phenylalanine Hydroxylase (Classic Phenylketonuria) or a deficit of Tetrahydrobiopterin Reductase. In both cases, the organism is not able to synthesize Tyrosine from Phenylalanine, so even when there is an accumulation of Phe in these patients, it can not be used to synthesize Tyrosine.

In fact, some of the signs and symptoms of Phenylketonuria, like mental retardation and other neurological symptoms, have been related to the unavailability of tyrosine for the synthesis of the neurotransmitters that derive from tyrosine.

The lack of pigmentation of PKU patients, has been related also to the lack of tyrosine, since Tyrosine is a precursor of melanine also.

It is obvious that if Tyrosine is formed in normal persons from phenylalanine through the reaction cited above, in case that this reaction can not be produced, like in PKU, it is necessary to supplement the patient with Tyrosine, since the patient can not synthesize it, so Tyrosine becomes an essential amino acid for these patients

Here is the first man to be cured of HIV- AIDS

Timothy Ray Brown, 45, from San Francisco Bay Area, is in the news – as the first man cured of HIV- AIDS. “I think so,” he calmly tells his interviewers who ask if he actually is cured.

Brown has been facing cameras, gun mikes and diagnostic kits ever since the publication of a research paper on his unique case in the journal Blood in December 2010.

The researchers led by Kristina Allers and Gero Hutter at Charite University Medicine Berlindocumented what can be dubbed as a miracle.

The successful reconstitution of a set of white blood cells that the HIV eats up in Brown’s body is a “very rare” occurrence, they noted.

Brown, who was tested HIV back in 1995 in Germany, was later diagnosed with another disease — leukaemia or blood cancer that involves an abnormal increase in white blood cell.

He was treated with bone marrow stem cell transplant — a cure for blood cancer. The stem cells came from a donor with a rare gene mutation that involves immunity to HIV — again a rare occurrence.

The mechanism involved special white blood cells called CD4+ helper T cells. When a dangerous material like a bacterium or a virus is detected in the body, immune cells immediately stimulate these special cells.

The helper T cells further activate and direct other immune cells to fight the disease. HIV specifically attacks helper T cells, making the body unable to launch a counter offensive against invaders.

Hence, AIDS patients suffer from other lethal infections. The researchers in Berlin showed that after stem cell therapy Brown’s body had reconstitution of CD4+ T cells at a systemic level and specifically in his gut mucosal immune system.

“While the patient remains without any sign of HIV infection,” they wrote. Brown has quit taking his HIV medication. The secret is that if the white cells could be manipulated to a state in which they are no longer infected or infectable by HIV that would mean a functional cure.

Researchers, however, have warned that though the study offers promise, it is not a surefire cure from the dreaded disease — transplants are risky, and this involved a very rare transplant. Brown is a rather lucky man. He said in a recent interview that appeared in the San Francisco media about his cure: “It makes me very happy — very, very happy.”

Scientists create synthetic brain cell

Researchers have for the first time created a synthetic synapse circuit whose behaviour duplicates the function of a brain cell.

A synapse is a junction that permits a neuron to pass an electrical or chemical signal to another nerve or brain cell.

The team, led by professors Alice Parker and Chongwu Zhou at the University of Southern California Viterbi School of Engineering, combined circuit design with nanotechnology to address the complex problem of capturing brain function.

Carbon nanotubes are molecular carbon structures a million times smaller than a pencil point. These nanotubes can be used in electronic circuits, acting as metallic conductors or semiconductors, according to a California statement.

'This is a necessary first step in the process,' said Parker, who began looking at the possibility of developing a synthetic brain in 2006. 'We wanted to answer the question: Can you build a circuit that would act like a neuron? The next step is even more complex.'

'How can we build structures out of these circuits that mimic the function of the brain, which has 100 billion neurons and 10,000 synapses per neuron?'

Parker emphasized that the actual development of a synthetic brain, or even a functional brain area is decades away.

The human brain continually produces new neurons, makes new connections and adapts throughout life, and creating this process through analog circuits will be a monumental task, according to Parker.

She believes the breakthrough could have long-term implications for everything -- from developing prosthetic nanotechnology to heal traumatic brain injuries to developing intelligent, safe cars that would protect drivers in bold new ways.

These findings were presented at the IEEE/NIH 2011 Life Science Systems and Applications Workshop in the US.

WHO says cell phone use can cause brain cancer

LONDON (Reuters) - Using a mobile phone may increase the risk of certain types of brain cancer in humans and consumers should consider ways of reducing their exposure, World Health Organisation (WHO) cancer experts said on Tuesday.

A working group of 31 scientists from 14 countries meeting at the WHO's International Agency for Research on Cancer (IARC) said a review of all the available scientific evidence suggested cell phone use should be classified as "possibly carcinogenic".

The classification could prompt the U.N. health body to look again at its guidelines on mobile phones, the IARC scientists said, but more research is needed before a more definitive answer on any link can be given.

The WHO had previously said there was no established evidence for a link between cell phone use and cancer.

"After reviewing essentially all the evidence that is relevant ... the working group classified radiofrequency electromagnetic fields as possibly carcinogenic to humans," Jonathan Samet, chair of the IARC group, said in a telebriefing.

He said some evidence suggested a link between an increased risk for glioma, a type of brain cancer, and mobile phone use.

The decision comes after a study published last year which looked at almost 13,000 cell phone users over 10 years found no clear answer on whether the mobile devices cause brain tumours.

The decision has been keenly awaited by mobile phone companies and by campaign groups who have raised concerns about whether cell phones might be harmful to health.

Use of cell phones use has increased dramatically since their introduction in the early-to-mid 1980s. About 5 billion mobile phones are currently in use worldwide.

(Reporting by Kate Kelland, editing by Alison Williams)