Question 1

Explain the role of citrate and succinate during inflammation in immune cells.
Citrate and succinate are two metabolites that play important roles in the regulation of
inflammation in immune cells. During inflammation, immune cells such as macrophages and
dendritic cells undergo metabolic reprogramming, which involves a switch from oxidative
phosphorylation to aerobic glycolysis. This shift in metabolism is necessary for the immune
cells to produce energy quickly and to generate the necessary building blocks for cell growth
and proliferation.
Citrate is an important intermediate metabolite that is produced during the first step of
the tricarboxylic acid (TCA) cycle, which is the metabolic pathway that generates energy
through the oxidation of glucose. In immune cells, citrate is exported out of the mitochondria
and into the cytoplasm, where it can be used for various biosynthetic pathways. One of the
main roles of citrate in immune cells is to act as a substrate for the production of
prostaglandins and other lipid mediators that are involved in the regulation of inflammation.
Citrate is also involved in the synthesis of amino acids and nucleotides, which are important
for cell growth and proliferation.
Succinate is another metabolite that plays an important role in the regulation of
inflammation in immune cells. During inflammation, succinate is produced through the TCA
cycle and the conversion of fumarate by the enzyme succinate dehydrogenase (SDH).
Succinate can activate a signaling pathway known as the succinate receptor pathway, which
leads to the production of pro-inflammatory cytokines and the recruitment of immune cells to
the site of inflammation. In addition, succinate can also stabilize hypoxia-inducible factor 1-
alpha (HIF-1α), which is a transcription factor that is involved in the regulation of
metabolism and inflammation (Harber, 2020).
Overall, citrate and succinate are two metabolites that play important roles in the
regulation of inflammation in immune cells. Citrate is involved in the production of lipid
mediators and biosynthetic pathways, while succinate activates a pro-inflammatory signaling
pathway and stabilizes HIF-1α. The regulation of these metabolites is essential for the proper
functioning of the immune system and the resolution of inflammation.

Question 2
Explain the role of high intensity exercises on white adipose tissue metabolism and
how it improves the cardiovascular system.
 High intensity exercises have been shown to have significant effects on white adipose
tissue (WAT) metabolism and cardiovascular health.
WAT metabolism: High intensity exercises increase the metabolic rate and energy
expenditure of the body, which promotes the breakdown of WAT and the release of stored
fatty acids. This process, known as lipolysis, leads to a reduction in WAT mass and a
decrease in circulating triglycerides and cholesterol levels. High intensity exercises also
stimulate the expression of genes that are involved in the oxidation of fatty acids, leading to
an increase in fat burning capacity. These metabolic changes in WAT have been linked to
improvements in insulin sensitivity and glucose metabolism.
Cardiovascular health: High intensity exercises improve cardiovascular health by
increasing the strength and efficiency of the heart muscle, improving blood vessel function,
and reducing inflammation. High intensity exercises promote the release of nitric oxide, a
vasodilator that improves blood flow and reduces blood pressure. They also increase the
expression of antioxidant enzymes that reduce oxidative stress and inflammation, which are
risk factors for cardiovascular disease. In addition, high intensity exercises have been shown
to improve the lipid profile of the blood, reducing levels of LDL cholesterol and increasing
levels of HDL cholesterol, which is protective against heart disease (Honkala, 2020).
In summary, high intensity exercises improve WAT metabolism by increasing
lipolysis and fat oxidation, and they improve cardiovascular health by improving blood vessel
function, reducing inflammation and oxidative stress, and improving lipid profiles. These
benefits have important implications for the prevention and treatment of obesity, type 2
diabetes, and cardiovascular disease.

Question 3
Explain the molecular mechanism of biotin in hair follicle production.
Biotin, also known as vitamin B7 or vitamin H, plays an important role in promoting
hair growth and maintaining healthy hair (Trueb, 2016). The molecular mechanism of biotin
in hair follicle production involves several key steps:
1. Biotin is essential for the production of keratin, a type of protein that makes up the
structure of hair. Biotin helps to activate enzymes that are involved in the production of
keratin.
2. Biotin also plays a role in the metabolism of amino acids, which are the building blocks
of proteins. This includes the amino acid cysteine, which is important for the formation
of disulfide bonds that give hair its strength and elasticity.
3. Biotin is involved in the production of energy within the hair follicle cells. This is
because biotin is a coenzyme that helps to activate enzymes involved in the breakdown
of glucose for energy.
4. Biotin may also have a direct effect on the hair follicles by stimulating cell proliferation
and differentiation. This means that biotin may help to promote the growth and
development of hair follicles.
Overall, the molecular mechanism of biotin in hair follicle production involves its role
in promoting the production of keratin, supporting the metabolism of amino acids, providing
energy to the hair follicle cells, and promoting cell proliferation and differentiation.
Understanding the molecular mechanism of biotin in hair follicle production is
important because it highlights the crucial role that biotin plays in maintaining healthy hair
growth and development. Biotin is an essential nutrient that is required for the proper
functioning of several enzymes involved in the synthesis of energy and fatty acids, both of
which are critical components of hair follicle production.
By serving as a cofactor for carboxylase enzymes, biotin plays a key role in the
conversion of amino acids and other substrates into energy and metabolic intermediates that
are used in the synthesis of keratin and other structural components of hair.

Question 4
Explain the effect of magnesium homeostasis on insulin release by pancreatic β-cells.
Magnesium is an essential mineral that plays an important role in insulin release by
pancreatic beta cells.
When blood glucose levels rise, pancreatic beta cells release insulin in response. This process
is regulated by several factors, including the concentration of magnesium ions inside the beta
cells. Magnesium ions are involved in several steps of insulin release, including the
depolarization of the beta cell membrane and the fusion of insulin-containing vesicles with
the cell membrane.
Intracellular magnesium levels in beta cells are tightly regulated by a balance between influx
and efflux of magnesium ions through ion channels and transporters. The magnesium
transporter 1 (MagT1) is an important regulator of magnesium homeostasis in beta cells. It is
highly expressed in beta cells and is involved in the uptake of extracellular magnesium into
the cells (Dastgerdi, 2022).
Several studies have shown that magnesium homeostasis plays an important role in insulin
release by beta cells:
1) Magnesium deficiency has been shown to impair insulin secretion in beta cells. This may
be due to a decrease in the activity of ion channels involved in beta cell depolarization
and calcium influx, which are necessary for insulin release.
2) Magnesium supplementation has been shown to improve insulin secretion in beta cells.
This may be due to an increase in the activity of ion channels and transporters involved
in magnesium influx, which can improve magnesium homeostasis in the cells.
3) Several genetic studies have identified variants in the MagT1 gene that are associated
with impaired insulin secretion and increased risk of type 2 diabetes. These variants may
disrupt magnesium homeostasis in beta cells and impair insulin release.
Overall, magnesium homeostasis plays an important role in insulin release by pancreatic beta
cells. Magnesium deficiency can impair insulin secretion, while magnesium supplementation
can improve it. Genetic variants that affect magnesium homeostasis in beta cells may also
contribute to the risk of type 2 diabetes.
 REFERENCES
Dastgerdi, A. H. (2022). The Therapeutic Effects of Magnesium in Insulin Secretion and
Insulin Resistance. Retrieved from https://doi.org/10.4103%2Fabr.abr_366_21
Harber, K. J. (2020). Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in
Macrophages. Retrieved from https://doi.org/10.3390%2Fmetabo10090372
Honkala, S. M. (2020). Exercise training improves adipose tissue metabolism and vasculature
regardless of baseline glucose tolerance and sex. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437884/
Trueb, R. M. (2016). Serum Biotin Levels in Women Complaining of Hair Loss. Retrieved
from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4989391/