ENZYME TRANSFERASES

 

         

Introduction

 

Enzymes 

They are proteins that act as a catalyst in living organisms, regulating the rate which chemical reactions proceed without it being altered.

Characteristics of enzymes

They are proteins in nature.

Speed up chemical reactions.

They’re required in minute quantities.

They are highly specific in their actions.

They are affected by temperature and pH.

Some require co-enzymes.

Some catalyze reversible reactions e.g. transferases

They can be inhibited by inhibitors

Mode of action of enzymes

An enzyme attracts substrates to its active site,catalyzes the chemical reaction by products are formed and then allows the products to dissociate i.e separate from the enzyme surface. The combination formed by an enzyme and its substrates is called the enzyme-substrate complex.

Factors affecting enzyme action

Concentration of substrate: increase in substrate concentration gradually increases the speed of enzyme reaction within the limited range of substrate concentration.

Temperature: increase in temperature increases the speed of enzyme reaction up to the optimum and then it declines. Optimum temperature for most enzymes is 40-45 degrees Celsius. Higher temperature above optimum denatures enzymes while lower temperatures inactivate enzymes.

pH: each enzyme has an optimum pH at which the speed of catalyzing is at maximum. Most enzymes of higher organisms show optimum activity around the neutral pH of 6.8-7.

Product concentration: accumulation of by-products decreases the speed of enzyme action. The byproduct combine with the active site to form a loose complex hence inhibits the enzyme.

Effect of activators: some enzymes require certain inorganic metallic cations for their optimum activity e.g magnesium, zinc, copper and sodium.

Time: the longer the enzyme will be incubated with its substrate, the higher the amount of product that will be formed. While the shorter the time of enzyme incubation with its substrate, the smaller the amount of product formed.

Transferases 

These are enzymes that catalyze the transfer of functional groups from one molecule to another. This makes these enzymes ideal catalysts for polymerization reactions. In nature, they are responsible for the synthesis of many important macromolecules

Types of transferases

Transketolase

Transketolase is an important enzyme in the non-oxidative branch of the pentose phosphate pathway (PPP), a pathway responsible for generating reducing equivalents, which is essential for energy transduction and for generating ribose for nucleic acid synthesis. Transketolase also links the Pentose Phosphate Pathway to glycolysis, allowing a cell to adapt to a variety of energy needs, depending on its environment. Abnormal transketolase expression or activity have been implicated in a number of diseases where thiamin availability is low, including Wernicke-Korsakoff's Syndrome and alcoholism. Yet, the precise mechanism by which this enzyme is involved in the pathophysiology of these disorders remains controversial.

Riboflavin synthase

Riboflavin synthase is an enzyme that catalyzes the final reaction of riboflavin biosynthesis. In its working mechanism, no cofactors are needed for catalysis. Additionally, the formation of riboflavin from 6,7-dimethyl-8-ribityllumazine can occur in boiling aqueous solution in the absence riboflavin synthase.

Phosphotransferase

Phosphotransferases are a category of enzymes that catalyze phosphorylation reactions. The Phosphotransferase catalyzes uptake of certain sugars, coupling membrane transport of its substrates with their phosphorylation. In addition to its transport function, the PTS is an important component of the signaling machinery that controls chemotaxis to its sugar substrates.

 The general form of the reactions they catalyze is:

A-P + B               {\displaystyle \rightleftharpoons }B-P + A

Where P is a phosphate group and A and B are the donating and accepting molecules, respectively.

The phosphotransferase works in a complex system a complex translocation group system present in many bacteria where it transports sugars such as glucose, mannose, and mannitol into the cell. The first step of this reaction is phosphorylation of the substrate via phosphotransferase during transport. In the case of glucose, the product of this phosphorylation is glucose-6-phosphate (Glc-6P). Due to the negative charge of the phosphate, this Glc-6P can no longer freely leave the cell. This is the first reaction of glycolysis, which degrades the sugar to pyruvate.

Peptidyltransferases

It is a primary enzymatic function of the ribosome, which forms peptide bonds between adjacent amino acids using transfer RNAs during the translation process of protein biosynthesis. The substrates for the peptidyl transferase reaction are two tRNA molecules, one bearing the growing peptide chain and the other bearing the amino acid that will be added to the chain. 

Peptidyl transferase speeds up the reaction by lowering its energy of activation. It does this by providing proper orientation for the reaction to occur. The peptidyl transferase provides proximity, meaning that it brings thing closer together, but it does not provide an alternate mechanism. Instead, it provides proper substrate orientation, increasing the probability that the existing mechanism will occur.

Kinase

A kinase is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule donates a phosphate group to the substrate molecule.

It works in form of Protein kinases (PTKs) which are enzymes that regulate the biological activity of proteins by phosphorylation of specific amino acids with ATP as the source of phosphate, thereby inducing a conformational change from an inactive to an active form of the protein.

Polymerase

A polymerase is an enzyme that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using base-pairing interactions or RNA by half ladder replication. DNA polymerase I and II are primarily required for DNA repair while DNA poly III is for the synthesis of DNA.

Transaldolase

Transaldolase is the enzyme of the non-oxidative phase of the pentose phosphate pathway that catalyzes the transfer of a dihydroxyacetone group. Unlike transketolase, which uses thiamine pyrophosphate to do the transferring, the transaldolase forms a Schiff base between the catalytic lysine residue and the substrate molecule.

Methyl transferase

Methyltransferases are enzymes that transfer methyl groups to their substrates resulting in substrate methylation.

Its function mainly in genetics is for Methylation, as well as other epigenetic modifications, affects transcription, gene stability, and parental imprinting. It directly impacts chromatin structure and can modulate gene transcription, or even completely silence or activate genes, without mutation to the gene itself.  Overall, it responds to mutations in DNA, signaling to the cell to fix them or to initiate cell death so that these mutations cannot contribute to cancer.

Sulfotransferase

These are transferase enzymes that catalyze the transfer of a sulfo group from a donor molecule to an acceptor alcohol or amine. The sulfotransferases comprise cytosolic and Golgi-resident enzymes; Golgi-resident enzymes represent fertile territory for identifying pharmaceutical targets. Structure-based sequence alignments indicate that the structural fold, and the Phosphoadenosine Phosphosulphate-binding site (PAPS), are conserved between the two classes.

Acyltransferases

Acyltransferases are a special group of lipases with highly enhanced affinity for other nucleophiles than water compared to classical lipases. In the presence of a suitable acceptor, they catalyze acyltransfer reactions such as alcoholysis, aminolysis, or perhydrolysis much faster than hydrolysis even in aqueous media with a high thermodynamic activity of water. This allows kinetically controlled reactions where the donor ester is fully converted into the ester product before any significant release of free fatty acids. 

References 

Rehm BHA, Steinbuchel A (2013) Introduction to Biological Macromolecules. Oxford, USA.

Doi Y (2011) Microbial Polysters. Wiley, New York 

Watson, James D. (2013) Molecular Biology. Upper Saddle River.

Boyce S, Tipton KF (2015) Enzyme classification and Nomenclature. Life sciences.

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Control and prevention of viruses

 Strategies for Control of Viral Diseases

Disease Control Through Hygiene and Sanitation

Intensive animal husbandry leads to accumulation in the local environment of feces, urine, hair, feathers, and so on, that may be contaminated with viruses; this is especially problematic with viruses that are resistant to environmental desiccation. To avoid this, intensive livestock units operate an “all in, all out” management system, by which the animal houses are emptied, cleaned, and disinfected between cohorts of animals. Hygiene and disinfection are most effective in the control of fecal–oral infections; they have much less effect on the incidence of respiratory infections. Efforts to achieve “air sanitation” are generally unsuccessful, especially in intensive animal production systems with high population densities.

Nosocomial Infections

Nosocomial virus infections are less common in large animal veterinary practices, where animals are usually treated on the farm, than in companion-animal practices. Appropriate management can reduce the likelihood of nosocomial infections, and veterinary clinics usually require that all inpatients have current immunization. Clinics should be designed for easy disinfection, with wash-down walls and flooring and as few permanent fixtures as possible. They should also have efficient ventilation and air conditioning, not only to minimize odors, but also to reduce the aerosol transmission of viruses. Frequent hand washing and decontamination of contaminated equipment are essential. Similar strategies are required in animal shelters where large numbers of cats and/or dogs may be cohoused in an environment that is highly conducive to explosive outbreaks of a wide variety of viral diseases.

Disinfectants and Disinfection

Disinfectants are chemical germicides formulated for use on inanimate surfaces, in contrast to antiseptics, which are chemical germicides designed for use on the skin or mucous membranes. Disinfection of contaminated premises and equipment plays an important part in the control of diseases of livestock.

Viruses of different families vary greatly in their resistance to disinfectants, with enveloped viruses usually being much more sensitive than nonenveloped viruses. Most modern disinfectants inactivate viruses, but their effectiveness is greatly influenced by access and time of exposure: viruses trapped in heavy layers of mucus or fecal material are not inactivated easily. There are special problems when surfaces cannot be cleaned thoroughly or where cracks and crevices are relatively inaccessible, as in old timber buildings or the fence posts and railings of cattle and sheep yards. New data on the effectiveness of standard disinfectants or the release of new products requires access to updated information on the correct use of disinfectants. 

Disease Control Through Eliminating Arthropod Vectors

Control of arbovirus infections relies, where possible, on the use of vaccines, because the large areas and extended periods over which vectors may be active make vector control difficult or, in many instances, impractical. However, surveillance of vector populations (eg, mosquito larval counts) and/or the climatic conditions conducive to vector transmissions over wider geographical areas provides the justification for local vector control, both as a preventive and as a control strategy. For example, aerial spraying with ultra-low-volume insecticides has been used to prevent the establishment of mosquito populations carrying encephalitis viruses in some parts of North America, although there are issues pertaining to increasing mosquito resistance and environmental objections. Some countries have based their emergency arbovirus control program plans on aerial insecticide spraying. This strategy is aimed at rapid reduction of the adult female mosquito population in a defined area for a very short time.

Organophosphorus insecticides such as malathion or fenitrothion are delivered as an ultra-low-volume (short-acting) aerosol generated by spray machines mounted on backpacks, trucks, or low-flying aircraft. Spraying of the luggage bays and passenger cabins of aircraft with insecticides reduces the chances of intercontinental transfer of exotic arthropods, whether infected or noninfected.

Exclusion of ticks has proven successful in the control of African swine fever in endemic regions; however, control is more difficult in free-ranging animals.

Disease Control Through Quarantine

Movement of domestic animals across international and even state borders can be regulated in countries where there are appropriate veterinary services and regulatory infrastructure. Quarantine remains a cornerstone in many animal disease control programs. A period of quarantine, with or without specific etiologic (eg, PCR) or serologic testing (see Chapter 5: Laboratory Diagnosis of Viral Infections), is usually a requirement for the importation of animals from another country, and similar requirements may be enforced within a country or region for the control or eradication of specific infectious agents.

As international movement of live animals for breeding purposes and exhibition has increased, so has the risk of introducing disease. Before the advent of air transport, the duration of shipment usually exceeded the incubation period of most diseases, but this is no longer the case. With the ever-increasing value of livestock, national veterinary authorities have tended to adopt stricter quarantine regulations to protect their livestock industries. Complete embargoes on importation are imposed for some animals by some countries. The concept of quarantine (Italian, quarantina: originally 40 days during which, in medieval times, ships arriving in port were forbidden to land freight or passengers if there was a suspicion of a contagious disease), where animals were simply isolated and observed for clinical signs of disease for a given period of time, is now augmented and often expedited by extensive laboratory testing designed to detect previous exposure to selected viruses or a carrier state. Laboratory testing requirements are set down in detailed protocols and are supported by national legislation.

Historically, the quarantine of animals has been a successful method for preventing the introduction of many diseases; however, other diseases may be introduced in animal products (eg, foot-and-mouth disease in meat products) or by virus-infected arthropods (eg, bluetongue). It must also be recognized that most countries have land boundaries with their neighbors and cannot control human and wildlife movement easily; thus, countries are expected to confirm their disease status to the World Organisation for Animal Health, which is the responsible international body. In addition to its central role in the reporting of livestock diseases globally, this organization also is responsible for harmonizing diagnostic testing and the creation of internationally agreed criteria for the safe movement of animals and animal products. However, problems persist that are often social, economic, and political rather than scientific—for example, smuggling of exotic birds may play a significant role in the introduction of Newcastle disease and fowl plague (highly pathogenic avian influenza) viruses into susceptible avian populations.

Disease Control Through Vaccination

Each of the foregoing methods of control of viral diseases is focused on reducing the risk of infection, whereas vaccination is intended to render animals resistant to infection with specific viruses. Immune animals cannot participate in the transmission and perpetuation of such viruses in the population at risk. Thus, vaccination can reduce the circulation of virus in the population at risk, as confirmed in countries where there is widespread vaccination of dogs against canine distemper and infectious canine hepatitis. Relaxation of vaccine usage, however, can have devastating consequences as, for example, in Finland in the 1990s, when canine distemper virus reemerged into a dog population in which vaccine usage had declined.

Safe and effective vaccines are available for many common viral diseases of animals. They are especially effective in diseases with a necessary viremic phase, such as canine distemper and feline panleukopenia. It has proved much more difficult to immunize effectively against infections that localize only in the alimentary or respiratory tracts.

Vaccination has been utilized extensively, and with varying success, in programs for the control and/or eradication of certain diseases. 

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Healthcare providers and their roles.

 Healthcare in Kenya

Photo courtesy: Peter Caesar
MMB Laboratory

This article is about Healthcare in Kenya. For the general health issues, see Health in Kenya.

Kenya’s health care system is structured in a step-wise manner so that complicated cases are referred to a higher level. Gaps in the system are filled by private and church run units.

Dispensaries and private clinics

Health centres

Sub-district hospitals and nursing homes

District hospital and private hospitals

Provincial hospital

National hospital

Health care units

See also: List of hospitals in Kenya

Dispensaries

The government runs dispensaries across the country and are the lowest point of contact with the public. These are run and managed by enrolled and registered nurses who are supervised by the nursing officer at the respective health centre. They provide outpatient services for simple ailments such as common cold and flu, uncomplicated malaria and skin conditions. Those patients who cannot be managed by the nurse are referred to the health centres.

Private clinics

Most private clinics in the community are run by nurses. In 2011 there were 65,000 nurses on their council's register. A smaller number of private clinics, mostly in the urban areas, are run by clinical officers and doctors who numbered 8,600 and 7,100 respectively in 2011. These figures include those who have died or left the profession hence the actual number of workers is lower.[citation needed]

Health centres

All government health centres have a clinical officer as the in-charge and provide comprehensive primary care. Because of their heavy focus on preventive care such as childhood vaccination, rather than curative services, local council (municipal) and most mission, as well as many private health centres, do not have clinical officers but instead have a nurse as the in-charge.

Health centres are medium-sized units which cater for a population of about 80,000 people. A typical health centre is staffed by:

At least one Clinical officer

Nurses

Health administration officer

Medical technologist

Pharmaceutical technologist

Health records information officer

Public health officer

Nutritionist

Driver

Housekeeper

Supporting staff

All the health centre staff report to the clinical officer in-charge except the public health officers and technicians who are deployed to a geographical area rather than to a health unit and report to the district public health officer even though they may have an office at the health centre.

The health centre has the following departments:

Administration block where patients register and all correspondence and resources are managed.

Out-patient consultation rooms where patients are seen and examined by clinical officers.

In-patient (wards) where very sick patients can be admitted. The wards are divided into male, female and paediatric with newborn units.

Laboratory where diagnostic tests are done. These laboratories can do the following tests: bloodslides for malaria parasites, sputum AFB, urinalysis, full haemogram, stool ova and cysts, blood sugar, Elisa and CD4 counts in comprehensive care centres for HIV/AIDS patients.

Pharmacy

Minor theatre where minor surgical procedures are done, e.g., circumcision, stitching wounds and manual vacuum aspiration

Maternity

Maternal and child health

Kitchen and catering

Student hostels for rural health training centres where students go to get rural experience.

Sub-district hospitals

These are similar to health centres with addition of a surgery unit for Caeserian section and other procedures. Many are managed by clinical officers. A good number have a medical officer and a wider range of surgical services.

Nursing Home

These are owned privately by individuals or churches and offer services roughly similar to those available at a sub-district or district hospital. They are also believed to provide better medical services compared to public hospitals.

Sub-County or District hospitals

Each sub county formally district in the country has a subcounty or district hospital which is the co-ordinating and referral centre for the smaller units. They usually have the resources to provide comprehensive medical and surgical services. They are managed by medical superintendents.

County hospitals

Kenya has 47 counties, each with a county hospital which is the referral point for the district hospitals. These are regional centres which provide specialised care including intensive care and life support and specialist consultations. It is the policy of many hospitals that those who do not pay their bills are not allowed to leave and may be prevented from doing so by armed guards. This policy was found to be illegal in September 2015 by the High Court but  was still widespread in October 2018, when the court again ruled that this “is not one of the acceptable avenues (for hospitals) to recover debt”. [1]

National hospitals

There are five national hospitals in Kenya, namely:

Moi Teaching and Referral Hospital

National Spinal Injury Referral Hospital

Kenyatta National Hospital

Mathare National Teaching and Referral Hospital

Kenyatta University Teaching and Referral Hospital

Maternal and child healthcare

The 2010 maternal mortality rate per 100,000 births for Kenya is 530. This is compared with 413.4 in 2008 and 452.3 in 1990. The under 5 mortality rate, per 1,000 births is 86 and the neonatal mortality as a percentage of under 5's mortality is 33. In Kenya the number of midwives per 1,00000 live births is unavailable and the lifetime risk of death for pregnant women 1 in 380. [2]

Ministry of Health

The Ministry of Health has its headquarters at Afya house in Nairobi. There is one minister for health, although there used to be two between 2008 and 2013 when Kenya had a coalition government.[3]

Director of medical services (DMS)

Provincial director of medical services(PDMS)

Provincial medical officer of health (PMOH)

Provincial health management board (PHMB)

Provincial health management team (PHMT)

Provincial hospital management team (P-HMT)

Sub-district hospital management board (SD-HMB)

District medical officer of health (DMOH)

District health management board (DHMB)

District health management team (DHMT)

District hospital management board (D-HMB)

District hospital management team (D-HMT)

Health centre management committee (HCMC)

Health centre management board (HCMB)

Health centre management team (HCMT)

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