GROUP ONE PRESENTATION

ON

BIOCHEMICAL EXPLAIN ACTIONS ON WHY RED BLOOD CELLS LACK NUCLEUS

AND

BRIEF WRITING ON THE RELATIONSHIP BETWEEN GLUTAMATE GLUTAMIC ACID AND

GLUTAMINE IN RELATION TO HAEMOGLOBINOPATHY

COURSE CODE BCH 406

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 WHY RED BLOOD CELL LACK NUCLEUS

Unlike the rest of the cells in your body, your red blood cells lack nuclei. That quirk dates back to the
time when mammals began to evolve. Other vertebrates such as fish, reptiles and birds have red cells that
contain nuclei that are inactive. Losing the nucleus enables the red blood cell to contain more oxygen-
carrying hemoglobin, thus enabling more oxygen to be transported in the blood and boosting our
metabolism.

Red blood cells are produced naturally in the bone marrow with a nucleus later they lose their nucleus in
order to accommodate more gases, losing the nucleus enables the red blood cells to contain more oxygen
carrying hemoglobin, thus enabling more oxygen to be transported to the blood and thereby boosting our
body metabolism. Evolution figured out it's more logical to just exclude them from the Red blood cells

Scientists have struggled to understand the mechanism by which maturing red blood cells eject their
nuclei. Now, researchers in the lab of Whitehead Member Harvey Lodish have modeled the complete
process in vitro in mice, reporting their findings in Nature Cell Biology online on February 10, 2008. The
first mechanistic study of how a red blood cell loses its nucleus, the research sheds light on one of the
most essential steps in mammalian evolution.

It was known that as a mammalian red blood cell nears maturity, a ring of actin filaments contracts and
pinches off a segment of the cell that contains the nucleus, a type of “cell division.” The nucleus is then
swallowed by macrophages (one of the immune system’s quick-response troops). The genes and signaling
pathways that drive the pinching-off process, however, were a mystery.

“Using a cell-culture system we were actually able to watch the cells divide, go through hemoglobin
synthesis and then lose their nuclei,” says Lodish, who is also a professor of biology at Massachusetts
Institute of Technology. “We discovered that the proteins Rac 1, Rac 2 and mDia2 are involved in
building the ring of actin filaments.”

“Rac 1 and Rac 2 were involved in disposing the nuclei of red blood cells,” says Peng Ji, lead author and
postdoctoral researcher in the Lodish lab. “These proteins are known for their role in creating actin fibers
in many body cells, and a necessary component of many important cellular functions including cell
division that support cell growth.”

His cell-culture system began with red blood cell precursors drawn from an embryonic mouse liver (in
mammalian embryos, the liver is the main producer of such cells, rather than bone marrow as in adults).
The cultured cells, synchronized to develop together, divided four or five times before losing their nuclei
and becoming immature red blood cells. The researchers used fluorescence-based assays that enabled
them to probe the changes in the red blood cells through the different stages leading up to the loss of the
nucleus.

The researchers plan to further investigate the entire process of red blood cell formation, which may lead
to insights about genetic alterations that underlie certain red blood cell disorders.“During normal cell
division, each daughter cell receives half the DNA,” comments Lodish. “In this case, when the red blood
cell divides, one daughter cell gets all the DNA. What’s fascinating is that in this case, that daughter cell
gets eaten by macrophages. Until now, scientists were unable to study these cells because they were
unable to see them.

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 OVERVIEW ON THE INDIVIDUAL AMINO ACIDS

Glutamate, glutamic acid and glutamine are all five carbon straight chain amino acid , having a common
carbon skeletal back bone, or are synthesized from Alpha ketoglutarate

GLUTAMATE

Glutamate is an amino acid and functions primarily as an

excitatory neurotransmitter in the central nervous system. It plays
a crucial role in various physiological processes,
including synaptic transmission, learning, and memory.
Glutamate is also involved in the regulation of neuronal development and plasticity. However, excessive
glutamate activity can lead to excitotoxicity, which is implicated in various neurodegenerative diseases,
such as Alzheimer's and Parkinson's disease.

Glutamate is synthesized through a process called transamination, which involves the transfer of an amino
group from an amino acid to a keto acid. In the case of glutamate synthesis, the amino group is transferred
from the amino acid α-ketoglutarate to another amino acid, usually alanine or aspartate, catalyzed by the
enzyme glutamate dehydrogenase or transaminases. Glutamate can also be synthesized from glutamine
through the action of the enzyme glutaminase, which removes an amino group from glutamine to form
glutamate.

Glutamate serves various functions in the body

1. Neurotransmission:Glutamate is the primary excitatory neurotransmitter in the central nervous system,

involved in signal transmission between nerve cells. It plays a crucial role in processes like learning,
memory, and synaptic plasticity.

2. Metabolism: Glutamate is a key player in amino acid metabolism, serving as a precursor for the
synthesis of other amino acids and proteins.

3. Energy Production: Glutamate can be converted into α-ketoglutarate, a key intermediate in the citric
acid cycle, contributing to energy production within cells.

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4. Neuronal Development:Glutamate is involved in regulating neuronal development and maturation,
influencing processes such as neurogenesis and synaptogenesis.

5. Regulation of pH: Glutamate participates in the maintenance of intracellular pH balance, helping to

regulate cellular homeostasis.

6 Osmoregulation:Glutamate plays a role in osmoregulation, helping to maintain the balance of water and
electrolytes within cells.

7 Neuroprotection: While excessive glutamate activity can be neurotoxic, moderate levels of glutamate
play a role in neuroprotection and antioxidant defense mechanisms within the brain.Overall, glutamate is
a multifunctional molecule essential for various physiological processes, particularly within the central
nervous system.

GLUTAMIC ACID

Glutamic acid, also known as glutamate, is a non-essential amino acid, meaning the body can synthesize
it on its own. It serves several important functions:

1. Neurotransmission:Glutamic acid acts as an excitatory neurotransmitter in the central nervous system,

playing a key role in signal transmission between nerve cells.

2. Metabolism: Glutamic acid is involved in amino acid metabolism, serving as a precursor for the
synthesis of other amino acids and proteins.

3. Energy Production:Glutamic acid can be converted into α-ketoglutarate, an intermediate in the citric
acid cycle, contributing to energy production within cells.

4. GABA Production:Glutamic acid can be converted into gamma-aminobutyric acid (GABA), a

neurotransmitter with inhibitory effects in the brain, through the action of the enzyme glutamate
decarboxylase.

5. Glutathione Synthesis: Glutamic acid is a component of glutathione, an important antioxidant

molecule involved in cellular defense against oxidative stress.

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6. Protein Structure: Glutamic acid, along with other amino acids, contributes to the structure and
function of proteins in the body.glutamic acid is a versatile molecule with diverse roles in metabolism,
neurotransmission, and cellular defense.

GLUTAMINE

Glutamine is a conditionally essential amino acid, meaning that while the body can typically produce it on
its own, there are circumstances where dietary sources become necessary. Glutamine is synthesized
through a process called glutamine synthesis, which occurs primarily in skeletal muscle and the liver. The
synthesis of glutamine involves the condensation of glutamate and ammonia, catalyzed by the enzyme
glutamine synthetase. This reaction requires the input of energy in the form of ATP (adenosine
triphosphate)

Glutamine can also be synthesized from glutamate through the action of the enzyme glutamine synthetase
in a reaction that incorporates ammonia. This process is essential for maintaining nitrogen balance in the
body and providing a source of glutamine for various physiological functions

Here are some key functions of glutamine:

Glutamine is the main source of fuel for the body lymphocytes, white blood cells that fights infection and
disease in order to keep the body healthy

Protein Synthesis: Glutamine is a crucial building block for proteins, playing a vital role in the synthesis
of muscle tissue and other proteins in the body.

Nitrogen Transport:Glutamine serves as a carrier of nitrogen between tissues, aiding in the removal of
excess ammonia from the body and supporting nitrogen balance.

Immune Function:Glutamine is essential for the proper functioning of the immune system, particularly for
cells involved in immune response and inflammation regulation.

Intestinal Health : Glutamine is important for maintaining the integrity of the intestinal mucosa and
supporting gastrointestinal health. It serves as a primary energy source for the cells lining the intestines.

Brain Function: Glutamine can cross the blood-brain barrier and serve as a precursor for the synthesis of
neurotransmitters like glutamate and gamma-aminobutyric acid (GABA), contributing to brain function
and neurotransmission.

Anti-oxidant Support: Glutamine plays a role in antioxidant defense mechanisms, helping to protect cells
from oxidative stress and damage.

80% of the body glutamine is found in the skeletal muscle, where it plays a key role in digestion and body
immune system

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RELATIONSHIP BETWEEN GLUTAMATE, GLUTAMIC ACID AND GLUTAMINE

Relationship
between
glutamate glutamic acid and glutamine in relations to haemoglobinpathy

The three amino acids can be use precursor to synthesize each other pending on the need and state of the
body , as fellows

Glutamine can be converted to glutamate through the action of the enzyme glutaminase. This conversion
typically occurs in tissues or cells where glutamate is needed for various biochemical processes, such as
neurotransmission in the brain or protein synthesis in the liver.through deamination reaction

Glutamine can also be synthesized from glutamate through the action of the enzyme glutamine synthetase
in a reaction that incorporates ammonia. This process is essential for maintaining nitrogen balance in the
body and providing a source of glutamine for various physiological functions, in a reaction know as
transamination reaction

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 GLUTAMINE AND HAEMOGLOBINOPATHY

The change/mutation of glutamine to valine lead to haemoglobinpathy condition know as sickle cell
anaemia this happens when the beta globin is mutated, the beta globin at the sixth position is mutated,
leading to the formation of abnormal protein cell haemoglobin S

The resulting haemoglobin tetramer(alpha2/beta2)is poorly soluble when deoxygenated

When this happens it changes the configuration given it a sickle shape instead of the round shape of
haemoglobin as seen in the image below

While normal red blood

cells last for 90 to 120 days, sickle
cell patients red blood cells last 10
to 20 days which the body may
not be able to keep up with how fast the cells are destroy leading to shortage in red blood cell level , a
condition known as anemia.

Sickle cell can block blood flow, cause pains and tissue damage.

The symptoms of sickle anemia varies from person to person but may include episode of pains in the body
part , such as hands feet lower back, chest and abdomen. Jaundice and feeling tired due to anemia, over
time sickle cell anemia can lead to complications such as severe pain and damage to eye , heart , lungs,
liver, kidney and joint

They can also cause damage to your spleen and other organs that makes immune cell

Treatment and management of sickle cell anaemia

Gene therapy

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Control of acute pains

Vaccines

Pain medications

Diet and activity restrictions

Sickle cell nephropathy

Treatment of other complications

Antibiotics

Hydroxyurea therapy

Transfusion e. t. c

Reference

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Ji, P., Jayapal, S. R., & Lodish, H. F. (2008). Enucleation of cultured mouse fetal erythroblasts
requires Rac GTPases and mDia2. Nature Cell Biology

increased risk of sickle cell disease among community-dwelling in adults and children: A systematic
literature review. Nutrition Reviews, 78(2), 175-188.

Kinlin, L. M. & Weinstein, M. (2023). Sickle : old disease, new lessons. Paediatrics and International
Child Health.

Trüeb, R. M., & Trüeb, R. M. (2020). Brief history of human nutrition. Nutrition for Healthy Hair: Guide
to Understanding and Proper Practice, 3-15.

Kumari, M., Sharma, D., & Sandeep, S. (2022). Biofortification of vegetable crops: an option for
mitigating hidden hunger. International Journal of Economic Plants, 9(3), 184-193.

Mwadiwa, R. J. (2022). Evaluating the socio-economic factors impacting on the dietary diversity people
in Sharpeville.

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