1. Teriflunomide Research Paper
Jia Yao
CHEM 130B Literature report
Dihydroorotate Dehydrogenase (DHODH) inhibitors
Malaria is transmitted by mosquitoes infected with parasitic protozoans(group of single–celled microorganism and belong to the Plasmodium genus)
Malaria is most commonly transferred by a bite of an infected female Anopheles mosquito1.
People infected with malaria often experience fever, chills, and flu–like illnesses and then they may develop severe complications and die if left
untreated.
Mosquitoes draws blood from the victim's body through the skin, injects saliva to stop the blood from clogging and if the mosquito is infected by
parasitic protozoans, then those are injected together with the saliva.
Those parasites find their way through the ... Show more content on Helpwriting.net ...
Among elderly; they may be more likely to develop burning, numbness, or tingling. Also it is not recommended to be taken if you have severe liver
problems or if you have abnormal liver function tests before taking teriflunomide.
It may also give blurred vision and may be worse if alcohol is consumed additionally.3
Teriflunomide also inhibits rapidly dividing cells, including activated T cells and tyrosine kinase enzymes, but only in high doses.The drug was
approved by the FDA on September 13, 2012.3
The binding site for teriflunomide is located at the narrow end of the channel where ubiquinone uses to accomplish a redox reaction with reduced
flavin mononucleotides.3 At Teriflunomide ,there are several charged and polar side chains (Gln47, His56, Tyr356, Thr360, Arg136). The deprotonated
enolic OH group interacts via hydrogen bonding with Tyr356, while the amide carbonyl is hydrogen bonded to Arg136 through a water
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2. Niacin And Vitamin B12 Metabolic Importance
Niacin and Vitamin B12 Metabolic importance
Vitamins are chemically unrelated organic compounds which can be used in many metabolic process. The vitamin B complex are water soluble
vitamins that are needed to form the coenzymes or enzymes in metabolic pathways. Niacin is used to produce NAD+ which is used in cellular
respiration and NADP+ used in the pentose phosphate pathway and would lead to someone developing pellagra. Additionally, vitamin B12 is used to
form cofactors required in the conversion of homocysteine to methionine an amino acid needed in the protein synthesis. Also in the isomerization of
methylmalonyl–CoA to Succinyl–CoA, an intermediate in the TCA cycle, and a deficiency can lead to the development of pernicious anemia ... Show
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The product of the reactions is fructose 1,6–bisphosphate. These steps in the glycolytic pathway are needed for the glucose to stay in the cell.
Additionally, the fructose 1,6– bisphosphate is easy to convert to phosphorylated three–carbon units. The second part of the glycolysis involves the
conversion of the fructose 1,6–bisphosphate into two different three carbon units which interconvert easily. In the third part, the three carbon units are
converted to pyruvate and there is a net production of two ATP. In thecitric acid cycle, the is a net production of 6 NADH molecules which can be
used in the electron transport chain. The NADH is produced by four Oxidation–reduction reactions where three pairs of electrons are transferred to
NAD+ and one pair to FAD (Ferrier, 2014).
Taken from– Biochemistry 5th edition
Fig 1– glycolysis
The diagram shows the metabolic process of glycolysis where glucose is trapped in the cell then converted to three carbon carbohydrates and lastly
ATP is produced. There is a net production of 2 ATP in glycolysis .Two NAD+ act as hydrogen acceptors to produce 2 NADH to be used in the electron
transport chain(Berg et.al , 2002).
Taken from– biochemistry 5th edition
Fig 2– citric acid cycle
This diagram shows the citric acid cycle where 6 NADH molecules are produced from NAD+ acting as a hydrogen acceptors. The product of
4. The Effect Of Plasma Metabolome Following Dietary...
Exam 2 Guoqing Wang 1.Metabolomic analysis of changes to plasma metabolome following dietary depletion and supplementation of thiamine
pyrophosphate (TPP) in mice Experimental design Male C57BL/6J mice (No. 11401300006402), weighing 20 В± 2 g, will be used for this experiment.
7–month old mice will be maintained in a room at 23 В± 2В°C and a relative humidity of 50 В± 10%, with a natural light–dark cycle. Food (6 mg
thiamine–HCl as the form of TPP) and water will be provided ad libitum. After acclimatization for 1 week, the mice will be divided into two groups
(n = 10 in each group) based on dietary difference: the dietary TPP depletion group (no TPP added) and the dietary TPP supplementation group (6 mg
thiamine–HCl/kg diet as the form of TPP). The supplementation level will be based on Nutrient Requirements of Laboratory Animals: Fourth Revised
Edition, 1995 [1]. Plasma samples will be collected from mice in each group before feeding the experimental diets and after 10–day feeding period, the
length of feeding experimental diets will be based on a previous publication [2]. Approach Plasma samples will be analyzed by H–NMR with or
without filtration and by targeted quantitative by mass spectrometry (MS) according to Gregory III et al., 2013 [3]. NMR spectral will feature selected
metabolites including acetyl–CoA, succinyl–CoA, acetoacetate and ribose. Expected results Compared to dietary thiamine supplementation at the
recommended level, thiamine depletion will decrease
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5. Vitamin C And Its Effect On Human Body
Chapter 1
1.Introduction
1.1.Vitamin B
Vitamins are a class of naturally occurring chemical compounds needed in fixed amounts for important body functions. They play important role in
energy generations, red blood cells and neurochemical production. They are micro–nutrients which are involved in the biological wear and tear of the
body and an important part of a balance diet. Since the human body cannot produce vitamins which are required in normal concentration; they can be
gained either from food sources or from dietary supplements. There are total of 13 kinds of vitamins needed by the human body comprising of vitamin
A, vitamin C, vitamin D, vitamin K and eight included in the group vitamin B (B1, B2, B3, B5, B6, B7, B9 and B12). Vitamin B group or complex
contains all the water soluble vitamins that play an important role in metabolism. Due to the watery composition of our body, these vitamins have the
ability to move inside our body and can be removed through urine without any difficulty. Thus, such vitamins are not stored by our bodies and need
replenishing on a daily basis. Fruits and vegetables are rich sources of vitamin B complex for the body. Processed foods lose their vitamin B content
thus through the process of enrichment as specified by food laws and regulations, the vitamin B is added into the food. Rich sources of vitamin B
include potatoes, whole grains, legumes, nuts, meat and fish. Due to their delicate chemical nature, vitamin B complex is
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6. Descriptive Essay On The Menil Museum
I recently visited the Menil Collection, this is a very small humble museum. The Menil Collection is a museum that holds multiple artworks. The
museum is located in a neighborhood next to a little area where people can go out and picnic and hang out with the their families for a while. I fact
about the Menil Collection that surprised me was how they consider their grass art. My sister and I accidently stepped on the grass not knowing it
was art and when we were handed a booklet describing a couple of their art pieces the grass was on their! The museum also has a couple of
sculptures and landmarks located right outside the building. Before stepping in into the museum I observed that it was very small, and I thought
there was not going to be any interesting art pieces since it was so small. The outside of the building was very simple, it was a white small building
with large windows, nothing that really caught my attention. Once we were greeted by the employee we collected a couple of brochures for the
background information of the artworks and we headed in. The first room of the museum really did not have any interesting art pieces, they were
basic squares and circles with primary colors. I really enjoyed how the art pieces were separated depending on their movement, such as
surrealism,abstract,and sculptures. There were many special exhibitions, the one that stood out the most to me was " Hurting the word Radio". This art
piece was created by Edward Ruscha using oil on
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7. Essay about Effect of Rotanone
Comparing LC50 of Insectisides Pirimicarb and Rotenone on Blowfly, Blowfly larvae, Woodlice and Daphni Abstract The LC50 of insecticides
rotenone and pirimicarb were compared by testing blowfly, blowfly larva, woodlice and daphnia. Rotenone is a NADH dehydrogenase inhibitor
causing death by oxidative stress however pirimicarb causes toxicity through acetylcholinesterase inhibition. It was found that rotenone had large
toxic effects on daphnia, blowflies and woodlice but not maggots and pirimicarb had low toxic effects on all of the organisms tested. Due to the low
percentage death caused by pirimicarb a LC50, however in rotenone a LC50 was performed for daphnia, woodlice and blowfly the LC50 for each
organism was compared concluding... Show more content on Helpwriting.net ...
Woodlice are nocturnal and are classified as primary decomposers, feeding on organic materials such as bark, leaves, dead plant and animal matter
and hardwood, decomposing the debris into soil which is vital for the ecosystem (Nardi 2009, Poole 1994 & CapineraI 2010). Woodlice can also
be classified as secondary decomposers as they feed on their own faeces to replenish the copper containing oxygen –absorbing pigment lost when they
defecate. Urine is also recycled in the water conducting channels along with water that is taken up from the environment, the ammonia of the urine
evaporates and from the remaining water in the water conducting channels oxygen is absorbed by pleopods (Nardi 2009). Daphnia, also known as
water fleas, are small crustaceans about 1mm–5mm long and are part of the freshwater zooplankton (Ebert 2005, Hutchinson 2005 & Clifford
1991). Daphnia can be found in most fresh water habitats such as freshwater springs, ponds and reservoirs and are the predominant food for
planktivorous fish. Dapnia are 'filter feeders' meaning they feed on small particles suspended in the water which can include algae. It has been found
that daphnia tend to migrate to the upper parts of the water at night and return to the lower parts of the water in the day to hide from predators (Ebert
2005) (Hutchinson 2005). Daphnia can reproduce through sexual reproduction and also asexual
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8. Presynaptic Neuron Research Paper
Neurotransmission also known as synaptic transmission is a process of communication between the neurons in the nervous system. It is a process in
which signaling molecules like neurotransmitters are released by neurons. Neurons are connected to one another. They receive information from other
neurons through synapses and process this information and then send it as an output to other neurons. This is called a neural network, a group of
neurons through which information flows from one neuron to other neuron. There are two types of neurons, the presynaptic neuron and the postsynaptic
neuron. Presynaptic neuron is the neuron that lies before the synapse and transmits the information across the synapse to another neuron. The neuron
that receives the information from presynaptic neuron is known as postsynaptic neuron. The process of this transmission between neighboring synapses
is very well organized, but it is quite different for transmission that is mediated by neuropeptides and nitric oxide. Before knowing the process behind ...
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In the figure, glutamate is released from presynaptic neuron and it binds to a receptor on the postsynaptic neuron. This process causes the opening of
Ca2+ influx, which leads to the activation of nitric oxide synthase. When NO is released it diffuses into the environment and interacts with presynaptic
membrane. NOS production is dependent on Ca2+ influx. It is also dependent on cofactors such as nicotinamide adenine dinucleotide phosphate
(NADPH), flavin adenine mononucleotide (FAD) and flavin mononucleotide (FMN). These cofactors are essential in the process of transfer of
electrons that produce NO. Due to NO's short lifetime it is very difficult to measure the production directly. However, it can be measured indirectly
though the correlation between Ca2+ and NOS. The details of NO's role in modulating cellular process in the nervous system are ignorant and need
future
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9. The Effect Of Glucose On The Glucose Of Glucose
Living organisms need to make energy from food in order to allow rapid cell reproduction and maintain life. Glucose, amino acids, and fatty acids are
utilized to generate adenosine triphosphate (ATP), a coenzyme used for an energy carrier. The primary source of carbon and energy for humans and
most eukaryotes is glucose [1]. But, since it is polar in nature, glucose cannot diffuse through the plasma membrane's lipid bilayer. This causes the need
for glucose to be transported by a glucose transporter, on the plasma membrane, into the cell. After the uptake of glucose, glycolysis is used to convert
the glucose into pyruvate. Glycolysis is a pathway that includes ten enzyme–catalyzed reactions.
When glucose enters the cell, it is phosphorylated by an enzyme, hexokinase, and uses ATP to keep the glucose concentration low in order to
continually transport glucose into the cell by the glucose transporters. This produces glucose 6–phosphate, which has a negative charge, preventing
glucose from diffusing out of the cell [2]. Glucose 6–phosphate is then rearranged by phosphoglucose isomerase to form fructose 6–phosphate.
Fructose 6–phosphate is catalyzed by phosphofructo–kinase–1 coupled with ATP, forming fructose 1,6
–bisphosphate. Since the molecule is now
destabilized, the fructose 1,6–bisphosphate is split by aldolase to form glyceraldehyde 3–phosphate and dihydroxyacetone phosphate [2].
Dihydroxyacetone phosphate is then converted into glyceraldehyde 3–phosphate by
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10. Vibrio Fischeri Is A Bacterium That Served As The Model...
Vibrio fischeri is a Gram–negative bacterium that served as the model organism in this experiment. We isolated only the luxAB portion of the entire
lux operon and inserted it into the pGEM vector plasmid to transcribe the luciferase enzyme required for bioluminescence. Within the lux operon,
luxAB is responsible for producing subunits that form luciferase, which oxidizes the aldehyde made by luxCDE into the reduced
flavin–mononucleotide FMNH2 and results in the production of light known as bioluminescence[6]. The luxI gene that is also present on the operon
produces the "autoinducer which interacts with a regulator, LuxR, [and] activates transcription of the lux operon at high–cell density" to induce
bioluminescence[4]. This interaction between the products of luxI and luxR is known as quorum sensing and serves as an evolutionary purpose in the
symbiotic relationship with Euprymna scolopes, a type of squid that contains the light organ where the bacteria resides[6].
In the first portion of the experiment, Vibrio fischeri chromosomal DNA was isolated by lysing the bacterial membranes and removing the proteins and
lipids. Addition of a lysozyme solution breaks down the peptidoglycan layer in Gram–negative bacteria and proteinase K/SDS degrades the proteins
and disrupt the membranes. Liquid–liquid extraction using Tris–buffered phenol permits separation of proteins and lipids from the DNA into the
organic layer. It is also essential that the isolated DNA is pure and free of
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11. Numerous stimuli activate eNOS (via phosphorylation) to...
Numerous stimuli activate eNOS (via phosphorylation) to generate NO, including vascular endothelial growth factor (VEGF), bradykinin and estrogen,
however the most potent activators of eNOS is shear stress, which is one of the most potent activators of eNOS.
Single Nucleotide Polymorphisms in eNOS gene
So far, several polymorphisms in the eNOS gene have been described, some of them being linked with the increased risk of CV diseases (Hingorani
AD).
A common polymorphism in exon 7 of the endothelial NOS gene is (894G>T) (Nadaud S et al). This results in a substitution of amino acid Glutamate to
Aspartate. (894G>T) polymorphism has been reported to be a strong risk factor for coronary artery diseases.
Studies using a reporter gene have ... Show more content on Helpwriting.net ...
et al 2004)
The aim of this study is to evaluate the manner in which different SNPs affect the biochemical activity of eNOS gene as well as its association with the
nitrite levels in patients of Pakistani populations.
Nitric oxide (NO) is synthesized from the amino acid L–arginine (precursor of NO) by the with the concomitant production of L–citrulline, and the
enzyme which catalyses its synthesis is called 'Endothelial Nitric Oxide Synthase' (eNOS). The catalysis of this reaction requires a number of essential
cofactors such as calmodulin (CaM), tetrahydrobiopterin (H4B), flavin mononucleotide, FAD, and NADPH (.Ingrid, B. Rudy 2003).
Regulation of eNOS
Production of NO is regulated by complex regulatory pathways. All isoforms of NO–synthases are activated when they bind with a specific calcium
regulatory protein: calmodulin. iNOS tightly binds calmodulin even at resting calcium concentrations, and then it is active once it is synthetized.
However, constitutive enzymes, eNOS and nNOS, only bind calmodulin when the intracellular calcium concentration increase up to a certain value.
Agents that increase intracellular calcium concentration, either by allowing calcium entrance from the outside or by stimulating calcium mobilization
from intracellular stores, can activate these constitutive enzymes Inspite of this calcium mediated regulation, recent research have shown that eNOS is
also regulated by pathways that are independent on changes in
13. Designing A Strategy For Increas Ing Riboflavin Production
Motivation: The objective of this set of practicals is to emulate the creation of a model describing riboflavin biosynthesis in Bacillus subtilis able to
support the development of a strategy for increas–ing riboflavin production.
Results: In this practical series, we walked through the practice of conceptualising a problem and experienced some software for pre–existing network
exploration in order to obtain information to solve it. This process led to the realisation of an ER model with high level of abstraction and a more
detailed reaction network map , realised in Cytoscape, describing in detail one of its modules: the Riboflavin Biosynthesis pathway. Moreover, the
consultation of integrated networks revealed im–portant aspects of the ... Show more content on Helpwriting.net ...
and Sibirny AA., 2011). Bacillus subtilis is a Gram–positive, cata–lase–positive and facultative aerobe bacteria, commonly present in soil as well as in
animals' gastrointestinal tract. It is used as a model organism for the study of chromosomal replication (Jakobs M. and Meinhardt F. 2015) and
sporulation (Yano K. et al. 2015) and, besides riboflavin production, it's also used in the industrial production of enzyme (Lan Thanh Bien T et al.,
2014) and biopol–ymers (Ju WT. et al., 2014). The modelling (or computational) approach consists in gathering as many information as possible
regarding the examined process and progressively, through the abstraction procedure, determining which part of them represents the variables in
control of it and that is therefore fundamental to describe consistently such phenomenon. The composition and the size of this information subset
depends on the abstraction level upon which we want to study the problem. The abstraction level is proportional to the number of different aspects of
the process (for example, the different species participating) that we want to take in consideration, and so to the amount of complexity we want to
describe the system with, and inverse proportional to the load of details incorporated in it. Later on, the development of a model concern
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14. The Effect Of Plasma Metabolome Following Dietary...
Exam 2
Guoqing Wang
1.Metabolomic analysis of changes to plasma metabolome following dietary depletion and supplementation of thiamine pyrophosphate (TPP) in mice
Experimental design
Male C57BL/6J mice (No. 11401300006402), weighing 20 В± 2 g, will be used for this experiment. 7–month old mice will be maintained in a room at
23 В± 2В°C and a relative humidity of 50 В± 10%, with a natural light–dark cycle. Food (6 mg thiamine–HCl as the form of TPP) and water will be
provided ad libitum. After acclimatization for 1 week, the mice will be divided into two groups (n = 10 in each group) based on dietary difference:
the dietary TPP depletion group (no TPP added) and the dietary TPP supplementation group (6 mg thiamine–HCl/kg diet as the form of ... Show more
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Data interpretation
TPP, the biologically active form ofvitamin B1, is an important enzyme cofactor in the mitochondria [4]. In addition, TPP participates as a cofactor of
transketolase in the pentose phosphate pathway, a cofactor of the О±–ketoglutarate dehydrogenase (О±–KGDH), pyruvate dehydrogenase (PDH) and
branched–chain О±–ketoacid dehydrogenase complex (BCKDC) [5]. Although loss of cofactor can explain in part for loss of enzyme activity,
thiamine and its phosphorylated derivatives may also regulate the mediate expression of genes encoding these proteins [6].
It has been reported thiamine deficiency decreases mRNA levels of transketolase and PDH but not О±–KGDH because there was no negative effect of
thiamine depletion on at least the E1 subunit of О±–KGDH [7]. This may also be explained by an attempt to maintain the activity of one enzyme over
the others preferentially, which agrees with riboflavin and enzymes that use it as a cofactor [8]. Therefore, thiamine deficiency may decrease the
abundance of acetyl–CoA and ribose, but not affect the abundance of succinyl–CoA. The E1О± subunit of the BCKDC participates in the
thiamine–dependent decarboxylation of branched–chain О±–ketoacids [9]. Therefore, thiamine deficiency may also decrease one of the products of
BCKDC, acetoacetate.
References
1.Benevenga, Norlin J., et al. "Nutrient requirements of laboratory animals."Nutrient
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