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Metabolism of Tay Sachs Disease

Since evolutionar, time living organism have always strives to maintain survival capability that further prolong their lives. Build in internal environmental surveillance, known as homeostasis had always enhance the organism ability to detect any damage and fix, the mistake before any substantial amount of damage can occurs. Normal function of this system is always under threat from pathogen and cell defects within the system that lead to condition that is characteristics as disease. The state of disease call Tay-sachs will be explored from the metabolic aspect of recurrent, to the medical or clinical events.
According to literature, Tay-sachs disease is known as “congenital ” neurodegerative disease that is cause by malfunction of lipids synthesis during cellular respiration or metabolism. In a normal cell lipids synthesis occurs in two functional states that alternate between degrading and synthesis of lipids. Changes to this particular normal cell programs is the results of a lipids condition that is called lipidose or diseases cause by the accumulation of lipids molecules in the body. From the biochemical stand point Tay-Sachs disease is causes by a number of enzymes, cell and metabolic activities that are no longer capable of performing their function that would have otherwise be present had it not been dysfunctionality of these specific enzymatic reactions. The enzymatic cells known to have involved in path way leading to creation of Tay-Sachs disease slightly varies but overall their cellular activities are the similar. According to ( Beutler, E), article entitle “The Biochemecal Genetics of the Hexosaminidase sytem in man”. Two members of carbohydrates sugar from a complex cell of glycolipids had been known to have causation of Tay-Sachs disease metabolic enzymes. The two carbohydrates are labels as ” N- acetylgalactosamines and N-acetyl-neuraminic acid” the two branches of sugar are the terminal point of gaglioside phospholipids in the cells. Both N-acetylneuraminic and N-acetyl acetyl galactosamines under normal circumstances are fill with abundance of enzymes that cleave the terminal points of the gangliosides molecule of “N-acetylneuraminosylgalactol-glucosylceramide”. The lack enzyme to catalyze the reaction with the above respective enzymes can results in “ganglioside accumulation” in the brain of the individual with any of the deficient enzymes. In the article entitle “Biochemical characterization of the GM2 gangliosidosis B1 variant” the metabolic characteristics of the of the Tay -sachs disease is dictate by action of the different enzyme preferably called “Beta hexosaminidase” or (Hex). Lysosomal or isoenzymes Beta hexosaminidase, according to (tutor, J.C) comes in two conformational parts the “hexosaminidase alpha, beta and hexosaminidase that contain two beta subunits”. The system of the four different subunits contain within the hexosaminidase are the content of the enzymatic activities of the cell metabolism to catalyzed the reaction. So under normal animals’ body physiological, homeostasis internal check points and catalytic enzymatics reactions, the Isoenzymes beta N acetylhexosaminidase will break down or hydrolyzed the reaction of the gaglioside activities.
This can result in disappearance of this nerves cell lipid that would have increase its byproducts at the level of the nervous system. Because isoenzymes beta N acetylhexosaminidase is divided into two subunits of enzymes mention early as beta, alpha and beta, beta subunits, each member of the enzymes is deploys to perform it respective function, given that system is operating under normal circumstances. For example isoenzymes beta N acetylhexoaminidase level a or containing subunits a will “participate” in the action of “degradation of the following molecules glycoproteins, gylcolipids and glycosaminoglycan” this will results in the breakdown of “Beta gylcocidic links of betan N acetylgulocosamine and beta N acetlygalactoamines”. Within the subunits of the isoenzmes beta N acetylyhexosaminidase, subunits apha and beta contain polarity charge that gives them the ability to bind to specific types of the cell, therefore leading to a desirable cell performance outcome. For instance, the lpha subunits contain an “active side that is negatively charge”, and small amount of “neutral charge”, but the beta subunits contains only “neutral charges”. The variants that is cause by the polarity, determine the side of the lipids cell each subunits will bind to resulting in the activation of isoenzyme beta N acetylhexosaminidase at the time of catalytic reaction events. In the case of alpha a subunit, which has a minus or negative charge, according to (tutor J.C) the “gaglioside bind alpha a subunits causing hydrolyzes of gaglioside” during enzymatic catalasis, at the same time the subunit beta does not bind to any of the gaglioside, because there is no attractive charges that would cause the two to bind to each other. The properties of the beta subunit liberate beta subunits from the causing any type hydrolization even when alpha subunit is not present.
The beta subunit property explains the lack of gaglioside breakdown in the present state of beta subunits. The present of Tay-Sachs disease will result from two variables, according to the literature studies showen the two variances are label as “B and B1 variant”. Variable letter B is going to be deficient in isoenzyme beta N acetylhexosaminidase, meanwhile letter b with one is going to have isoenzyme beta N acetylhexoaminidase that lack a “cataylix or mutated isonzyme”. The mutation will cause a non functional side chain of the acetyhexosaminidase from reaction with gaglioside side of negatively charge groups. In addition the mutation will specifically act on the “gaglioside activator proteins” preventing the activator protein from binding to the substrate of side of the isoenzyme. The general consequence, action of this protein, added with behavior of both gaglioside products and isoenzyme beta N acetylhexosaminidase results in biochemistry path way of gaglioside not being hydrolyzes by the enzyme resulting in a condition called the Tay-sachs disease.
Because the biochemical reaction that result in gaglioside build up is known, one is left to asked why would alpha and beta subunits of the isoezyme beta N acetylhexosaminidase would cause enzymatic catalytic deficiencies? From the genetics stand point this question can be answer base on nucleic acid genetics or genes component. According, to inherited health web side article, a person is bone with type two type of gene that are responsible for enzymatic catalysis of” beta-hexosaminidase genes call hexa”. The main altermate goal for the hexa genes in the cells, during cellular differentiation is to direct the hexa genes to produces or turn into beta hexosaminidase isoezymes. The actions of the hexa genes is comprise as a results of the mention in the cells, the mutation “disrupt” the cellular machinery of the hexa genes from performing their normal cell functions. So the question a rise, how do someone get the hexa genes that is the causation for the lack of hexosaminidase enzymatic deficiency in the cells? Given that mendellian genes flow dictate how genes are passed from one generation to the next generation, this question can be explained by following basic mendel, theory of inheritance. According to mendel theory of inherit ant of gene, for the individual to receive defective hexa genes deficient in hexosaminidase enzyme catalytic activities. Two events must occur in order for the organism to inherent the genes. Both parents of the organism mother and father must be a carried of the defective genes, for the gene to be passed on to the offspring or progeny. Which mean that both parents were heterozygote for the copy of the mutated gene and each must passed the bad gene or mutated gene copy of the gene to the child resulting in autosomal recessive alle. The inherent recessive alles copy of the gene is now present in two copies in the cells of the progeny organism. Because the gene pattern of inherent is directly in control, of the type cellular function, each genes is suppose to do in the cell, this is the reason the mutation of hexa genes is important in lysosomal enzymatic activities. So the question is how does a mutation that have cause a defective in the hexa gene lead to or related to Tay-Sachs disease? According to the article on Genes and disease from the nation center for biotechnology information, there is a direct correlation relationship between mutation on the hexa genes and neurodegerative disease that result in Tay – Sachs disease. Research showed that it is the hexa gen that “code for the alpha subunit of the enzyme beta-hexosaminidase A”. During normal condition “Beta-hexosaminidase a help to degrade a lipid called GM2 gaglioside, but in tay-sach individuals the enzyme is absent or present only in very reduce amount, allowing excessive accumulation of the GM2 gaglioside in neurons”. In addition research, showed that the three component that are involved in tay sach disease are “alpha subunit, beta subunit and G activator” it is believes that lack or low functioning of the alpha subunit of the “hexosaminidase malfunctions leads to a toxic build up of the Gm2 gaglioside in the lysosomes” organel compartment of the eurkayotic cells.
The condition of Tay-Sachs disease as it related to the two form of organism both prokaryote and Eukaryote has not been indentify between these two organism. Either because there has not been any research done on prokaryote organism, regarding the present or the absent of the tay sach disease concerning the availability of tay sach in this population of organism, prokaryotes. Other plausible explanation, because prokaryote lack compartmentalized organelle that house content such as lysosomes , may just simple not present with this group. Since the pathway of the disease is dictate by the enzymatic breakdown of the in the lysosomal organelle prokaryote will not have this condition. In Eukaryotes within the organism, other than human, in mice the same type of GM2 gaglioside lipid that cause high level of lipid build up in human, was also indentify in mice. The “activator proteins ” in mice is defective, therefore mice is not able to hydrolyzed fat storage in their systems resulting in neurological characteristics similar to those observed in human, however the condition is not called Tay-sachs. On the contrary, the conditions in mice also exhibit some differences with those condition observed in human. For example the lipid “storage in mice is in the cerebellum and developed defects in balance and motor coordination”. The differences in mice and human are the results of “Gm2 gagliosidoses are species specific differences in the gaglioside degradation pathway”.
The actual illness, expression of the tay sach disease condition can be very debilitating, not only does the Tay-Sachs cause severe neuron damage but the segment of the population that effected tend to be young children. The national library of medicine and genetic reference home page define tay sach disease as “a rare inherited disorder that progressively destroy nerve cell or neurons in the brain and the spinal cord”. Some the symptoms associated with the above definition, that result from the action of the tay sach disease include, ability of decrease in motor function such as running, walking sitting and jumping. Most of the above symptoms can be observed in children, particularly infant groups. As the child grow in age the prognosis of the disease stage, begin to progress at higher speed rate, the child develops symptoms such as “seizures, vision, lost of hearing mental retardation and eventually paralysis”. This condition will result in loss of life for the individual person that is affected by the disease. Tay-Sachs disease is not only prevalence in the young or the infant group but can be observe in other groups such the adolescent to adult and the severity of the disease varies from the groups to and groups. The symptoms similar those observed in children are also observe in adults, specifically the “weakness in muscles coordination characterizes as “ataxia”. According to the research, Tay-Sachs disease is found to be less common in overall population of the society, but at the same time it is common with specific group of the populations. The availability of the disease with sub category of the population is attributes to genes behavior, since genes are passed on from one generation to next generation. The literature agrees on the most common segment of population that Tay-Sachs disease is the most prevalence, members of “Ashkenaki eastern and central European Jewish ancestry”. Also the other groups were the members of the “north western Spain and northern Portugal”. It is important to mention that those group mention above are not the only affected groups but instead, region where a higher than expected incident rate can be seen. It is worthwhile to note that all human population of the world have case of the Tay-Sachs disease, except that symptom varies with within subpopulation.
Following, the present of the Tay-Sachs disease symptoms and diagnosis or testing must be carried out from the clinical point of view to determine the cause of tay sach symptoms or for any other disease for that matter. Base on the article entitle ” hexosaminidase deficiency” testing is apply to confirmed or disprove the present or absent “beta hexosaminidase A enzymatic activity in the serum or white blood cells of the a symptomatic individual in the presence of normal or elevated activity of the beta-hexosaminidase B isoenzyme”. Lack of the normally high level of beta hexosaminidase in the blood or present in small amount would indicate the present of Tay-Sachs disease. This particular type of testing is sometimes refer to as “biochemical testing” because the expert is searching for the level of the damage or inefficient enzymatic chemical processes. Other type of testing that is used some time would be “carrier testing” and the testing is perform on groups, whom their one or two members of their family is known to be the carrier of the mutated gene in other heterozygote. Both tests are effective in identifying the gene or the disease with the exception of each testing being specific to each condition.
Treatment and management of Tay-Sachs disease is difficult to apply due to lack of the therapeutic drugs to cure Tay-Sachs disease. Some of the expert recommendation is gear toward things like proper nutrition and large amount of fluid to keep the body from dehydration. Symptoms such seizures can be management by providing the patients with anticonvulsant prescriptions drugs, such as”benzodiaxepines, phenytoins or barbituarate”. These drugs are use to maintain or manage the seizure part of the Tay-Sachs disease. Psychiatric drugs can be used for individual that are having metal episode these can drugs like antidepressant. According to the literature some treatments have showed a promising outcome, such treatment with “lithium salts and electroconvulsive therapy has been reported to be beneficial, at least in amenliorating for the period of the episode of psychotic depression”.
Currently according to the literature there are some neuronal procedure being, investigate to find the cure for Tay sach disease. Some of the experimental produce included “central nervous system enzyme replacement therapy”. The idea would be to find synthetic enzymes that will mimic the activity of the hexosamidase isoenzyme taking over the place or natural enzyme. In addition to genetic engineering of the organism cell such as mice can also be utilizes to treat “innovative treatment modalities”. Other recent invention, such blocking the enzymatic biosynthesis activities of “glycoshingolipids of a GM2 gaglioside. Research indicates that these ongoing experiment and successive result have not been achieved at this point.
Given that organism is bone with internal mechanism to fight out infectious, diseases once cannot estimate the important of knowledge base skill to solved problems. Although currently Tay-Sachs disease does not have therapeutic prevention, because of many research studies devote to this disease one hope, that there will be cure in the future. Because the resilience and persistence character of human being far out weight any challenges faces society. This was a interesting topic, which have result in learning some of the biochemical aspect of the disease from biochemistry at a cellular level.

Research into the Hepatitis B Virus

Hepatitis B is an infectious illness caused by hepatitis B virus which infects the liver of humans, and cause an inflammation called hepatitis (World Health Organization, 2010). It is formerly known as ‘serum hepatitis’, the disease has caused a widespread outbreak that infects many people at the same time in parts of Asia and Africa, and specific regional in China. There are more than 2 billion people who have been infected with the hepatitis B virus, including 350 million chronic carriers of the virus (Wikipedia 2010). They are a viral infection that can lead to serious illness or death.
Hepatitis is defined as the inflammation of the liver that can be caused by viruses, alcohol, drugs and other toxins, or less commonly by a breakdown in a person’s immune system (Hepatitis Australia, 2010). There are five types of viruses that can cause infection of the liver and may produce similar symptoms. They are hepatitis A, hepatitis B, hepatitis C, hepatitis D and hepatitis E. The main difference between the hepatitis viruses is how they are transmitted and the effects they have on a person’s health. Hepatitis is described as either an acute or chronic illness, the acute illness will only last a short time and despite the fact it can be severe, most people recover from the illness within a few weeks with no lasting effects. A chronic illness will last for a long time, often for the rest of a person’s life. Hepatitis B is the most common liver infection in the world and is caused by the hepatitis B virus which is the virus that affects the liver which can cause pain and swelling (Hepatitis Australia, 2010). The infection leads to damage of cells in the liver which can cause the organs to not function properly (Oxford Medical Dictionary, 2010).
How is HBV transmitted? Well HBV is a very infectious virus. It can be transmitted by infected blood or blood products contaminating hypodermic needles, blood transfusion, or tattooing needles, or by unprotected sexual contact (Better Health Channel, 2010). This can happen with people that have unsafe sex by not using a condom or someone who gets a body piercing or a tattoo if the person doing the piercing or tattooing is not very careful with making sure that everything is very clean (disinfected and sterilised does not happen). It also happen to people on drugs who shared needles with each other and also if someone steps on a needle that has been used by someone using drugs. HBV can also be transmitted by family members who have been infected such as sharing razor blades or toothbrushes (Kids Health, 2010)
Also an infected mother might pass it to a newborn baby at the time of the baby’s birth. In the research article of ‘Perinatal transmission of hepatitis B virus: an Australian experience’ , it states that “reported rates of transmission from mothers who are positive for hepatitis B “e” antigen vary from 7% to 28%.” The research article concludes that the mothers who had Hepatitis B “e” antigen-positive have very high viral loads. So a mother who is positive for Hepatitis B surface antigen have a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for Hepatitis B “e” antigen (Wiseman et al. 2009). Mothers who are bound to Hepatitis B “e” antigen positive who have very high viral loads meaning having a severe viral infection, this is referring to the research article ‘perinatal transmission of hepatitis B virus: an Australian experience’.
After exposure to HBV (Hepatitis B virus), it can cause acute or chronic infection (Margaret, F (ed.), 2006). Acute infection usually last a short time but they can make you feel uncomfortable with signs and symptoms. If a person is unable to clear the hepatitis B virus from their system after a period of time, the person is said to be chronically infected (Wrong Diagnosis, 2010). Chronic infection means continuous damage to the liver, which can result in cirrhosis, liver failure, hepatocellular cancer, and even death. Patients infected during childhood are at greatest risk for developing chronic hepatitis B infection. (Centers for Disease Control, 2010).
The HBV is a double stranded DNA virus that comes from the group Hepadnaviridae (eMedicine Medscape 2010). HBA is a hepatotropic virus meaning it has a special attraction for the liver, which it prefers to infect the liver over and any other part of the body (Medical Dictionary: The free dictionary, 2010) thus it replicates in the liver and cause hepatic dysfunction. The virus is made up of a nucleocapsid and an outer envelope that consist three main hepatitis B surface antigens (HBsAgs) that is part of a role in the diagnosis of HBV infection. It is thought that this virus causes inflammation of the liver by inducing apoptosis (programmed cell death) which then causes HBV-induced liver injury (Baumert, et. al 2007)
The liver is an organ that has many important roles in our body; we cannot live without a liver. The liver helps remove harmful chemicals from your blood, it fights infection, helps digest food, store energy, and also store nutrients and vitamins. The liver is the only organ in the body that has the capability to regenerate itself and make new liver tissue (NDDIC, 2010)
The hepatitis viruses that generate into a chronic infection have what it takes to cause liver damage because the virus reproduces in the liver. The process fibrosis occurs after some time has gone pass, more of the liver cells will become damaged and destroyed which will cause the scar tissue to take place. If the fibrosis is severe it can cause the liver to become hardened, and it will keep it from working normally which is called cirrhosis of the liver. (Hepatitis Australia, 2010).
In a small number of cases, serious damage to the liver can lead to liver failure and liver cancer. (Hepatitis Australia, 2010).
A long duration of infection with hepatitis B virus may be associated with a long duration inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. This type of infection will greatly increase the incidence of Hepatocellular Carcinoma (Wikipedia, 2010) so this is the reason why Hepatitis B Virus exposure may lead to the development of Hepatocellular Carcinoma.
The hepatitis B virus can cause illness which can last for several weeks but for some people they do not become ill, their symptoms may be flu-like or some do not become sick at all. Children are less likely to have symptoms than adults when infected. A person with the infection will feel tired and lose their appetite which can last for many weeks. Their skin and eyes will look yellow, this is called jaundice. Their urine will look very dark and they may feel nauseous which can lead to vomiting a lot. They might have pain in their joints, pain in their liver and also have a fever. (Kids Health, 2010)
There are also itchy skin signs which could a possible symptom for all hepatitis virus types. The illness lasts for a few weeks and then gradually improves in most affected people. A few patients may have more severe liver disease and may die as a result of it. (Better Health Channel, 2010)
To detect whether you have Hepatitis B infection or not, a liver function test must be carried out. First the doctor or nurse will check your blood to see if your liver is working normally. When the liver function test is carried out, it measure the levels of enzymes found in the liver, heart and muscles. The Enzymes are the proteins that cause or increase chemical reaction in the living organisms. The laboratory tests include Bilirubin, AST, ALT, Alkaline Phosphatase, GGT and LDH. (The Body, 2010)
Bilirubin is like a yellow fluid produced when red blood cells break down. If you have high levels, this can indicate liver disease but might also be caused by the antiviral drugs indinavir (Crixivan) and atazanavir (Reyataz). (The Body, 2010).
AST which stands for Aspartate Aminotransferase, it is used with the ALT test to detect liver disease. (The Body, 2010).
ALT stands for Alanine Aminotransferase; it is used with the AST test to detect liver disease. (The Body, 2010).
Alkaline Phosphatase if you have high levels of this, it indicates that you may have liver or bone disease. (The Body, 2010).
GGT stands for Gamma Glutamyl Transpeptidase, this tells you if the results can show whether other abnormal test results are due to liver problems or bone problems. (The Body, 2010).
LDH stands for Lactic Dehydrogenase; it is a normal indicator of tissue damage (The Body, 2010)
There is also liver biopsy where it involves by removing a small piece of tissue from the liver by just using a fine needle. The tissue is then examined under a microscope to look for inflammation or liver damage and alpha-fetoprotein is a blood test which can sometimes detect liver cancer. (The Body, 2010)
People with hepatitis B have no signs of illness and do not realise they have the virus in their body so hepatitis B is diagnosed through different kind of blood tests, which look for markers of the hepatitis B virus in the blood. (Hepatitis Australia, 2010)
Figure 1: Here is a table that gives an understanding of the Tests (Hepatitis Australia 2010)
Test Abbreviation What is shows Hepatitis B surface antigen
Shows that the person is infected with hepatitis B which can be detected during acute and chronic infection.
Hepatitis B surface antibody
HBsAb or Anti-HBs
Shows that the person has developed immunity to hepatitis B which can be detected in people who have recovered from hepatitis B or been vaccinated against hepatitis B.
Hepatitis B e antigen
Shows that hepatitis B virus is multiplying.
Hepatitis B e antibody
HBeAb or Anti-HBe
Shows that the person’s immune system has responded against hepatitis B and the virus is not actively reproducing.
Hepatitis B core antibody
HBcAb or Anti-HBc
Shows that the person is infected with hepatitis B which can be detected during acute and chronic infection.
Hepatitis B virus DNA
Shows that the person has developed immunity to hepatitis B which can be detected in people who have recovered from hepatitis B or been vaccinated against hepatitis B.
(Hepatitis Australia 2010)
The antigen is the foreign substance in the body, such as the hepatitis B virus and the. And the antibody is a protein that the immune system makes in responses to a foreign substance (Hepatitis Australia, 2010)
Normal references values. For ALT test if a person (Age 80 U/L (units per litre), they could have Mixed hepatocellular and cholestatic disease. But they have 90 U/L it could result to Cholestatic liver disease or bone disease. But if their result is <90 U/L then are in the isolated elevated ALP which resulting to high serum ALP. (Melbourne Pathology, 2010)
For predominant Hepatocellular Pathology, result of ALT or AST Or >150 U/L; ALP <200 U/L results can be cause by an infection such Hepatitis A, B, C. (Melbourne Pathology, 2010)
A study of perinatal transmission of HBV was conducted between August 2002 and May 2008. The people who participated were pregnant women who attend Sydney South West Area Health Service antenatal clinics and they were tested positive for hepatitis B surface antigen (HbsAg), also their babies. The babies for hepatitis B surface antigen undergo 9 months follow up for further virological testing which involves HBV DNA sequencing. The pregnant women have a clinical and biochemical assessment which includes tests for their liver enzymes, Hepatitis B virus DNA and Hepatitis B “e”antigen. (Wiseman et al. 2009).
Before November 2006, the study used laboratory methods to test for Hepatitis B virus in pregnant women and their babies. Hepatitis B virus serology was performed using the AxSYM microparticle enzyme immunoassay (Abbott Laboratories); it is a technique in which the solid-phase support consists of very small microparticles in liquid suspension. (Mondofacto, 2010)
The research shows that 213 mothers out of 313 have detected with HBV DNA which 91 HBeAg were positive. Out of the 213 mothers there were 115 who have low viral load, 29 with high viral load and 69 had very high viral load. (Wiseman et al. 2009).
Conclusion To conclude hepatitis B are the most common infectious diseases in the world and is a serious problem for people who has it and that we need to be careful for it. It is a virus that can cause inflammation to the liver which can be found in blood and body fluids. There are acute hepatitis and chronic hepatitis