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Lecture 5
Lecture 5
Micronutrients
•‘Micro’ means small.
•Micro-nutrients are the organic substances required by the body in small
quantities or diminutive compared to macro-nutrients.
•In simple terms, vitamins can be water-soluble vitamins, fat-soluble vitamins
and minerals can be macro-minerals and trace minerals.
VITAMINS A, D, E, AND K are ARE FAT-SOLUBLE VITAMINS A, D, E, AND K are ARE FAT-SOLUBLE
VITAMINS A, D, E, AND K are ARE FAT-SOLUBLE VITAMINS A, D, E, AND K are ARE FAT-SOLUBLE
VITAMINS VITAMINS
Vision Maintenance: Vitamin A is crucial for preserving the Hair Growth: Adequate levels of vitamin A support healthy hair
function of light-sensing cells in the eyes and for the production growth. Deficiency can lead to alopecia, causing hair loss or
of tear fluid, contributing to overall eye health. thinning.
Immune Function: Deficiency in vitamin A can weaken the Reproductive Health: Vitamin A plays a role in maintaining
immune system, fertility and is crucial for fetal development during pregnancy,
Body Growth: Vitamin A is essential for cell growth, particularly Food Sources and Intake: Vitamin A is primarily found in animal-
in children. derived foods such as liver, fish liver oil, and butter.
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VITAMINS D VITAMINS D
Vitamin D is a general name for vitamins D3 and D2. Their structural
difference is vitamin D2 has a double bond, that vitamin D3 does not
have, in the hydrocarbon chains attached to the five-membered ring. Bone Maintenance: Vitamin D regulates calcium and
phosphorus levels
Calcium Absorption: Vitamin D promotes Vitamin D2 has a double here Immune System Regulation: It strengthens immune function
calcium absorption in the gut, ensuring Sunlight Synthesis: Vitamin D synthesis occurs in the skin upon
adequate serum calcium and phosphate exposure to sunlight.
concentrations, crucial for normal bone
mineralization, growth, and remodeling.
Sunlight Synthesis: is synthesized in the skin
upon exposure to sunlight.
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VITAMINS D VITAMINS D
Deficiency Risks: Risk factors for deficiency include older age, obesity, Once absorbed into the bloodstream, your liver and kidneys change
and diseases affecting fat absorption. Deficiency can result in soft calciferol into calcitriol, which is the biologically active form of
bones, muscle weakness, and increased fracture risk, along with vitamin D. It can also be stored for later use in the form of calcidiol.
impairments in immune function.
Toxicity Concerns: While sun exposure does not cause toxicity,
excessive supplementation can lead to hypercalcemia, characterized
by elevated blood calcium levels.
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VITAMIN E VITAMIN E
VITAMIN K VITAMIN K
Blood Clotting: Vitamin K is essential for proper blood clotting, Deficiency Risks: Unlike some vitamins, vitamin K isn't stored in
obtained from foods like green leafy vegetables and synthesized large amounts in the body. Deficiency can occur rapidly,
by intestinal bacteria. Its coenzyme form, vitamin KH2, plays a particularly in individuals with fat malabsorption conditions like
vital role in this process. celiac disease or those on broad-spectrum antibiotics. High
Bone Health and Heart Disease Prevention: supports bone vitamin A doses may also hinder vitamin K absorption.
health and prevents blood vessel calcification, potentially Impact on Blood Clotting: Mega-doses of vitamin E can
lowering heart disease risk. counteract vitamin K's blood clotting effects.
WHAT IS STEROID?
Structural Composition: Steroids, classified as lipids, consist of a tetracyclic
ring system with designated A, B, C, and D rings. The A, B, and C rings are six-
membered, while D is a five-membered ring. Trans-fused rings are more
common due to their stability.
Biological Importance: including hormone production, cell membrane
formation, and gene regulation. Cholesterol, the most abundant steroid in
animals, serves as the precursor for vitamin D, bile acids, and other steroids.
Physiological Effects: Steroids exhibit unique properties due to their trans-
fused ring structure, enabling interactions with cell receptors. This
interaction can lead to diverse physiological effects, including muscle mass
enhancement, strength improvement, and increased endurance.
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WHAT ARE STEROID HORMONES? (2) Mineralocorticoids
Many hormones are derivatives of steroid. – cause increased reabsorption of Na+, Cl-,
and HCO3- by the kidneys, leading to an
Hormones are chemical messengers – organic compounds increase in blood pressure
synthesized in glands and delivered by the bloodstream.
– e.g. aldosterone
They are usually attached to carrier proteins to target tissues in order
to stimulate or inhibit some process.
There are 5 classes of steroid hormones: (3) Androgens
– belong to sex hormones and are secreted
primarily by the testes
(1) Glucocorticoids – are responsible for the development of
– are involved in glucose metabolism male sex characteristics during puberty,
– participate in the metabolism of proteins including muscle growth
and fatty acids. – e.g. testosterone
– e.g. cortisone: it has anti-inflammatory
– e.g. 5-dihydrotestosterone: derived from
effect and is used clinically to treat arthritis
testosterone through enzymatic
and other inflammatory conditions.
conversion by 5α-reductase, further
24 contributes to the development of male
secondary characteristics such as growth
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of facial and body hair, voice deepening,
(5) Progestin
– prepares the lining of the uterus for
implantation of an ovum
– is essential for the maintenance of
pregnancy
– e.g. progesterone
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Why is the microenvironment [1] Tumor immunology
http://wirtzlab.johnshopkins.edu/research/tumor-microenvironment/
Microenvironment – not just the Microenvironment
cells [2] Signaling molecules
G-CSF
Erythropoietin
[2] Signaling • [4] Extracellular matrix G-CSF (Granulocyte-Colony Stimulating Factor): Stimulates
molecules – Collagen neutrophil production in the bone marrow, crucial for immune
G-CSF system restoration post-chemotherapy or transplantation.
Erythropoietin – Fibronectin
Dysregulation can lead to conditions like leukemia.
[3] Cell-cell contact – Laminin Erythropoietin: Produced by the kidneys, stimulates red blood cell
Adherens junctions
Gap Junctions
• [5] Forces production in the bone marrow, maintaining blood oxygen levels.
Desmosomes – Elasticity Used clinically to treat anemia, especially in patients with kidney
disease or undergoing chemotherapy.
– Compression
Clinical Utility: Both G-CSF and Erythropoietin are commonly
– Stiffness employed in clinical settings to manage various conditions,
highlighting their significance in medical treatment.
Maintaining Homeostasis
Microenvironment Microenvironment
[3] Cell-cell contact (next week) [4] Extracellular matrix
Adherens junctions – Collagen, Fibronectin
Gap Junctions
Desmosomes – Laminin
•
Microenvironment Microenvironment
[4] Extracellular matrix [5] Forces
Collagen: Most abundant protein providing structural
support to tissues. Forms fibers imparting tensile
– Elasticity
strength. In the tumor microenvironment, collagen – Compression
remodeling can impede immune cell infiltration and – Stiffness
promote tumor invasion.
Fibronectin: Glycoprotein crucial for cell adhesion and
migration. Overexpression in the tumor
microenvironment forms networks supporting tumor
growth and angiogenesis.
Laminin: Glycoprotein vital for cell adhesion and
differentiation. A major component of basement
membranes, forming a physical barrier between tissue
compartments. Overexpression contributes to tumor
invasion and metastasis.
Microenvironment Microenvironment
[5] Forces [5] Forces
Elasticity: The ability of a material to deform and return to its Compression: Force exerted on a material when squeezed or
original shape. Changes in tissue elasticity influence cell compressed. In the tumor microenvironment, compression
behavior, migration, and invasion. Tumors, typically stiffer than affects tumor behavior, including angiogenesis and immune
surrounding tissue, promote cell migration and invasion, infiltration. It can also lead to hypoxia, promoting tumor
contributing to drug resistance. aggressiveness.
Microenvironment Stem cell behavior control
[5] Forces Adult stem cells such as intestinal crypt stem cells are tightly
regulated by the environment around them
Stiffness: Resistance of a material to deformation when force is Sometimes mutations cause bad behaviors
applied. In the tumor microenvironment, stiffness influences
cell behavior, proliferation, and differentiation. Tumor stiffness
contributes to drug resistance and limits therapy efficacy.
https://www.youtube.com/watch?v=t3g26p9Mh_k
Blood cell differentiation Blood cell differentiation
Granulocyte Colony Stimulating Factor (G-CSF):
G-CSF promotes the development of granulocytes,
• Multipotent stem cells differentiate into a including neutrophils, eosinophils, and basophils, from the
macrophage through a series of steps that are common myeloid progenitor (CMP) cell.
Erythropoietin (EPO):
regulated by signals and transcription factors. EPO specifically stimulates the production of red blood
• The steps involved in the differentiation of a cells
Clinical Applications:
multipotent stem cell into a macrophage are: G-CSF is used to stimulate white blood cell production in
commitment, differentiation, migration, maturation, neutropenic patients, while EPO is employed to treat
and activation. anemia caused by insufficient red blood cells.
Anchoring junctions
Two types: adherens and desmosomes
Built from cadherins (outside) and catenins (inside)
Adherens: attach to actin cytoskeleton
Desmosome (strong): attach to keratin filaments
Gap junctions
Channels between cells
[3] Types of Cell interactions [3] Types of Cell interactions
Tight junctions Anchoring Junctions Overview:
• Seal the gaps Provide mechanical stability and anchor cells to each other or to the
extracellular matrix.
between adjacent Include two main types: adherens junctions and desmosomes.
cells, Adherens Junctions:
Anchor cells together by forming connections with the actin
• Maintaining integrity cytoskeleton.
of epithelial and Built from transmembrane proteins called cadherins and intracellular
endothelial cell layers proteins called catenins.
Important for tissue structural integrity, cell-cell adhesion, and
• Form a fluid and ion signaling.
impermeable sheet Desmosomes:
Provide strong adhesion between cells by forming connections with
• Allows for different cytoskeletal intermediate filaments.
functions on different Composed of transmembrane proteins (desmogleins and
sides of the sheet desmocollins) and intracellular proteins (desmoplakin).
Critical for maintaining tissue integrity, particularly in mechanically
stressed tissues like the skin and heart muscle.
Forces Cancer
Uncontrolled growth (proliferation)
Experimental Evidence: Invasion into surrounding tissues
Studies with mesenchymal stem cells grown on gels of Metastasis (spread to other areas in body)
differing stiffness reveal distinct differentiation patterns:
Soft environments promote neuronal differentiation Key terms:
(brain-like stiffness). Malignant: Describes cancerous cells or tumors capable
Intermediate environments prompt muscle cell of invading nearby tissues and spreading.
differentiation (muscle-like stiffness). Proto-oncogene: Normal genes involved in cell growth
Stiffer environments stimulate bone cell regulation, which when mutated, can become oncogenes.
differentiation (bone-like stiffness). Oncogene: Mutated or activated genes promoting
uncontrolled cell growth and division, contributing to
cancer development.
Tumor suppressor gene: Genes that normally inhibit cell
growth, but when mutated, lose this ability, facilitating
cancer development.
Communication is important!
Objectives
● Signal transduction
The process by which a cell
responds to an extracellular signal
What is cell signaling?
GROWTH
Cancer Cancer Syndromes
FACTOR
PIP3 p
Hamartin Tuberin
Raf (Tuberous Sclerosis TSC1 TSC2
Complex)
P
(Ras-homology
MEK
P P P P P P
enriched in brain)
RheB Inhibitors to PI3K and/or
P
BAD NF-ĸB FKHR MDM2 GSK3 p70S6K Akt are being developed
(Target of rapamycin) mTOR for patient use
ERK
S6K 4EBP-1
Cell growth/size/survival Kovich & Cohen (2004) Dematology Online Journal 10: 3.
. Aaronson, Growth factor and receptor tyrosine kinases. Sci. STKE 2005, tr6 (2005). Perelman (2004) Dematology Online Journal 10: 17.
Crosstalking among different
signaling REFERE
pathways NCES
1. P. Y. Bruice, Organic Chemistry, Pearson Education,
New Jersey, 5 ed., 2007.
th
and 21).