Assign. 1: Question 1 Surname, First Name. a).Glucose m

Assign. 1: Question 1 Surname, First
Name
a).Glucose metabolism is the main source of biological energy used in the sustenance and maintenance
of life processes [1]. In the very first chemical step of this metabolic cycle, glucose molecule is first
transported across the very plasma membrane by an action of facilitative glucose transporter flowing
down and across the physiologically active concentration gradient. Hexokinase is an enzyme present in
the mitochondria which then phosphorylates the glucose molecule to a compound called glucose-6-
phosphate (G6P) [2]. This product (Glucose 6 phosphate) then enters into the glycolytic pathway where
it generates molecules of ATP, NADH and then pyruvate. Glucose 6 phosphate may also enter the
pentose phosphate pathway which plays a very vital role in nucleic acids synthesis (both Ribonucleic
acid and deoxy-ribose nucleic acid) along with the production of NADPH – that assists in regulation of
intracellular homeostasis (redox) and synthesis of lipids.
The biological process is called glycolysis. The end products of glycolysis are two Pyruvate, two
NADH (Nicotinamide adenine dinucleotide) and two ATP (adenosine triphosphate).
In presence of enough amount of oxygen, the pyruvate from glycolysis cycle enters into the
mitochondria and then gets fully oxidized in order to release more molecules of ATP. When amount of
oxygen is very limited, it is seen that pyruvate gets transformed to lactate. Hence, glycolysis is the prime
source of main energy reservoir that is adenosine triphosphate (ATP).
b). Citric acid cycle is pivotal biochemical cycle occurring inside the very matrix of mitochondria.[2]
The first metabolic step of this cycle is a vitally crucial step which fuses the two-carbon acetyl group
(from acetyl CoA) with four-carbon molecules of oxaloacetate to forge an entity of six-carbon molecule-
citrate. Citrate gets converted to its isomer known as isocitrate. In step-three of this cycle, iso-citrate is
totally oxidized, releasing an important five-carbon molecule called alpha ketoglutarate. The CoA then
binds the succinyl group, forming an entity succinyl CoA. This energy that is released in the
phosphorylation process occurring at the minute substrate level (during the biological conversion of the
succinyl group to a reduced form of succinate) forms new ATPs. Step six reaction of the citric acid cycle
is dehydration reaction which changes succinate into fumarate. Next, water is then added to fumarate
during feasibility of step seven, resulting in formation of the malate. Then, the very last step occurring in
the citric acid cycle produces oxaloacetate by the oxidation of malate. Then another NADH molecule is
produced. The major end products of the citric acid cycle are ten NADH molecules, two
FADH2 molecules, two ATP molecules and six Co2.
c). Oxidative phosphorylation happens or takes place as a vital biological event in the inner
mitochondrial membrane [3], very much in contrast with most of the biological(respiratory) reactions of
the citric acid cycle and fatty acid oxidation, which happens to take place in the mitochondrial matrix.
NADH reductase, succinate dehydrogenase, ATP synthetase, complex III and IV cytochrome c oxido-
reductase are the major trans-membrane enzymes catalyzing the electron transport chain and oxidative
phosphorylation in an efficient way after completion of citric acid cycle. The fine mechanism of action
of these highly functional enzymes are critical to the feasibility of this imperative biological process.
d). Oxygen’s function is vital at the very end of reactions occurring in electron transport chain and this is
where the oxygen molecule accepts new electrons while picking up protons to form new molecules of
water. If oxygen is absent or not adequate to accept electrons (a person is breathing in compromised
aerobic sphere for instance), the electron transport chain will cease to function and the ATPs will be no
longer produced by the action of chemiosmosis. Without adequate amount of ATP, cells would not be
able to carry out biological reactions which are important for catabolic process and after persisting for a
period of time, the cells can even die.
References
1. Parhofer KG. Interaction between glucose and lipid metabolism: more than diabetic
dyslipidemia. Diabetes & metabolism journal. 2015 Oct 1;39(5):353-62.
2. Springsteen G, Yerabolu JR, Nelson J, Rhea CJ, Krishnamurthy R. Linked cycles of oxidative
decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle. Nature
communications. 2018 Jan 8;9(1):91.
3. Zheng X, Boyer L, Jin M, Mertens J, Kim Y, Ma L, Hamm M, Gage FH, Hunter T. Metabolic
reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative
phosphorylation. Elife. 2016 Jun 10;5:e13374.

Assign. 1: Question 2 Surname, First
Name
a). The sequence of events are as follows:-
 End plate potentials (EPPs) are actually the bioelectric voltages that cause depolarization in
the fibers of skeletal muscle acted-in by bio- chemical neurotransmitters [1]. These
neurotransmitters then finds a way to bind to the target postsynaptic membrane which exists
around the nearest neuromuscular junction. These postsynaptic terminals are known as "end
plates" as because they are saucer like in shape and opens in the muscle fibers.
 When the developmental action potential travels down and on reaching the axon of
concerned motor end neuron, the vesicles with neuro-excitatory transmitter (acetylcholine) are
released into the proximal nerve- muscle junction.
 Then, these acetylcholine molecules fixes themselves into the target molecular receptors
which are present on the postsynaptic side.
 End plate potential are chiefly elicited by fixation of acetylcholine molecules into the target
receptors within the post neuronal membrane. Two types of receptors which has been
discovered are: nicotinic, muscarinic.
 When the action potential invokes the chemical release from various acetylcholine vesicles,
the molecules of acetylcholine diffuses out and across the proximal junction that fixes to a
group of nicotinic receptors present on linings of the muscle fiber.
 This process allows the enhanced flux of potassium, sodium ions.
 This leads to excitatory depolarization of the muscle cell membrane known as sarcolemma.
b).Though, the concerned insecticide is designed to kill insects but certain insecticides have an
anticholinesterase property [2], strong enough to induce dreary effects if consumed into human
system. These insecticides can lead to poisoning. That is why the parents should be worried rightly
and a thorough medical checkup must be done immediately before onset of any severe symptoms.
c). Dermal exposure of the cholinesterase insecticide can unfortunately leads to biologically
hazardous nicotinic effects which again depends on the intensity and amount of exposure [3]. Dermal
exposure can progress to symptoms like local twitching which can then cause muscle fasciculation(s)
with signs of weakness. There can be a delayed but very progressive, severe muscular paralysis.
d). Respiratory symptoms such as shortness of breath (dyspnea), wheezing and bronchial problems
can be as seen. Muscarnic effects of insecticide poisoning leads to muscle weakness and medical
emergency such as cardiovascular, respiratory collapse [4]. The human sympathetic and
parasympathetic system can also be equally affected, leading to lacrimation and urinary incontinence.
e). Atropin can be used as an antidote [5]. Large doses of atropine, can block dreary autonomic
effects of anticholinesterase. The medication can be provided in conjunction with a cholinesterase
regenerator drug. An effective airway needs to be critically managed to counter the development of
allergic dyspnea. Assistance with artificial ventilation is of course centralized in accordance with
patient requirements. Seizure precautions, lavage and seizure management is medically necessary and
so is the promotion of good hygiene in the patient. Frequent turning and patient rollover activities on
bed are also integral to the nursing interventions in preventing bed rest complications.
References
1. Zanetti G, Negro S, Megighian A, Pirazzini M. Electrophysiological Recordings of Evoked
End-Plate Potential on Murine Neuro-muscular Synapse Preparations. Bio-protocol. 2018 Apr
20;8:e2803.
2. Vale A, Lotti M. Organophosphorus and carbamate insecticide poisoning. InHandbook of
clinical neurology 2015 Jan 1 (Vol. 131, pp. 149-168). Elsevier.
3. Raabe OG, Al-Bayati MA, Knaak JB. Physiologically based pharmacokinetic modeling to
predict tissue dose and cholinesterase inhibition in workers exposed to organophosphorus and
carbamate pesticides. 2017 Nov 22 (pp. 19-46). CRC Press.
4. Guo-Ross SX, Meek EC, Chambers JE, Carr RL. Effects of Chlorpyrifos or Methyl Parathion
on Regional Cholinesterase Activity and Muscarinic Receptor Subtype Binding in Juvenile
Rat Brain. Journal of toxicology and pharmacology. 2017;1.
5. Huang HS, Lee KW, Ho CH, Hsu CC, Su SB, Wang JJ, Lin HJ, Huang CC. Increased risk for
hypothyroidism after anticholinesterase pesticide poisoning: a nationwide population-based
study. Endocrine. 2017 Sep 1;57(3):436-44.

Assign. 1: Question 3 Surname, First
Name
a). The reflex elicited by Jodie is crossed extension reflex. Further neuronal circuitry is required to
render the flexor reflex as adaptive. As because during standing or walking, the weight of the body is
always and generally supported by both legs – a flexor reflex is a chief mechanism by which the
execution of physical activity is not just imposed on the weight bearing leg while being withdrawn
but coordinated together with the opposite leg. We can imagine Jodie stepping on the very sharp
prickle with bare leg, and she had her flexor reflex withdrawing her right leg immediately. Her left
leg was seen to automatically extend to assist her entire body weight which was meant to be done by
her right leg alone under the circumstances of the given incident. This fine neural coordination of the
two legs allows the rapid swing in body mass without which, the situation can manifest an immediate
loss in balance. The neuronal mechanism of this flexor inducing reflex incorporates what is known as
a crossed extension reflex [1]. A nerve bundle or a branch of group three afferent nerve fibers
innervates the very fast acting inter neuron which travels or passes into the contralateral section of
spinal cord. Then, the bundle of alpha motor neurons undergoes an excitatory phase - exciting the
extensor group in the other leg, allowing a functional posture with correct balance to be achieved.
b).The reflex is patellar reflex. Striking or jerking the patellar tendon with a neurological hammer,
below the level of patella stretches the spindle present inside the quadriceps group of muscle [2]. This
action creates a neural signal which conducts faster and backwards, upwards to the spinal cord where
it synapses (without any interneurons) at a level of Lumbar L3 in the lower spinal cord. This action is
perhaps completely free of any cortical control. Then, a fast alpha motor neuron conducts a rapid
impulse backwards to the quadriceps group of muscle, triggering a vigorous shortening (a muscle
contraction). This strong contraction along with flexor group relaxation of hamstrings forces the
concerned leg to suddenly pull. This type of proprioceptive reflex is critically helpful in maintenance
of balance and posture. The reflex also allows to hold one's own balance with very less contribution
or effort from a higher consciousness. This patellar reflex is an exquisite clinical example of a single
synapse mediated reflex arc.
c). Golgi tendon structures or organs are physiologically active anatomical structures which are fast
excited by a quick or stretch induced shortening of a working muscle, transmitting a neural signal
regarding the muscular inner tension[3]. An excitation of these Golgi tendon organs receptors results
in the functional inhibition of working muscle through the action of a myotatic reflex acting
inversely. GTOs are always located very near to the point of muscle joint attachment and are
localized in the tendons. Each Golgi tendon organ consists of a very delicate capsule – carrying
inside, a group of collagenous fibers. The sensory neurons innervates the very collagen containing
fibers present within the thin capsule which are again entwined with branches of other collagen
containing fibers. These afferents then conducts the vital information about the concerned muscle’s
tension to the sections of spinal cord. The crucial ‘signal’ is then transduced to higher cortical centers
and to the functioning cells of cerebellum controlling the efferent (motor) pathways. With the action
of this reflex, an inversely acting myotatic reflex is produced simultaneously that has both dynamic,
static components. When the fiber tension in the muscle goes up rapidly, a vigorous response is then
elicited.
References:
1. Dafkin C, Green A, Olivier B, Mckinon W, Kerr S. Circadian variation of flexor withdrawal
and crossed extensor reflexes in patients with restless legs syndrome. Journal of sleep
research. 2018 Oct;27(5):e12645.
2. van Munster CE, Weinstein HC. LETTER RE: The plantar reflex: A study of observer
agreement, sensitivity, and observer bias.
3. Crago PE. Neuromodulation by combined sensory and motor stimulation in the peripheral
nerve: tendon organ afferent activity. Journal of neural engineering. 2018 Dec
12;16(1):016015.

Assign. 1: Question 4 Surname, First
Name
Part 1:
a. Milligrams of creatinine secreted over last 24 hours is = 30 * 960 = 28800 mg
b. Amount of creatinine cleared per hour = 28800/ 24 = 1200 mg/hour
c. c. Creatinine clearance is 71.4ml/min.
Formula used: Creatinine clearance = Ucr * Uvol/ Pcr* Tmin [1]
d. GFR is found to be 2.08 ml/min/1.73m2 using the abbreviated MDRD equation.
e. The GFR reading is suggestive of a stage 5 chronic kidney disease. Diabetes, hypertension
and renal artery stenosis can be underlying causes for such a severe presentation at such a
young age.
Part 2:
f) The level of aldosterone will increase after taking the drug.
g) The sodium concentration in the Steven’s blood will increase after taking in the drug. Aldosterone
plays a very critical role in homeostatic control of human blood pressure by acting on the
reabsorption mechanism of plasma potassium and sodium levels. Aldosterone functions by acting on
the mineralocorticoid receptors present in the renal distal tubules. Aldosterone also has a vital
mechanism of action on the renal collecting tubules located inside the nephrons. It influences the
urgent reabsorption of sodium ions from the tubular fluids with excretion of potassium into the same
fluid, thereby altering and influencing the level of water retention, blood volume, osmolality and
hormonal regulation of blood pressure [2].
h). Water reabsorption would also increase in the kidneys, leading to an increase in blood pressure.
Antidiuretic hormone or vasopressin would retain water as such as possible for the regulation of
rapidly falling blood pressure. In other words, vasopressin raises the blood pressure.
i) Anti Diuretic hormone which prevents the process of diuresis, would increase (after taking in the
drug) the retention of water and salt in the body. The main function of this hormone in human body is
to control the volumetric level of extracellular fluid by regulation of the renal water retention by
vasoconstriction. Vasopressin or ADH acts on nephron’s collecting ducts through V2 receptors to
enhance water permeability.
j) Water secretion would be reduced after taking in the drug because of increased salt and water
reabsorption in the convoluted tubules, owing to the action of raised anti-diuretic hormone.
References:
1. Haeseker M, Croes S, Neef C, Bruggeman C, Stolk L, Verbon A. Evaluation of vancomycin
prediction methods based on estimated creatinine clearance or trough levels. Therapeutic drug
monitoring. 2016 Feb 1;38(1):120-6.
2. Lozić M, Šarenac O, Murphy D, Japundžić-Žigon N. Vasopressin, central autonomic control
and blood pressure regulation. Current hypertension reports. 2018 Feb 1;20(2):11.