Vit A Flashcards

1
Q

What is vitamin A?

A

A group of structurally related compounds classified as retinoids
-naturally occuring or synthetic compound that is structurally similar to all-trans retinol (with or without vit A activity)
-including retinol, retinal, retinoic acid, and retinyl esters

Includes provitamin A carotenoids like β-carotene found in plant foods.

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2
Q

What is the main form of Vit A?

A

All trans retinol

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3
Q

What are dietary forms of preformed vit A? what does this mean?

A

Retinol (retinyl palmitate and retinyl acetate), retinyl ester,retinal, and retinoic acid

these are biologically active forms of vit A that are found in animal derived foods

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4
Q

What are the characteristics of fat-soluble vitamins?

A

Stored in liver and adipose tissue, require lipids for absorption, higher risk for toxicity due to accumulation

Includes vitamins A, D, E, K.

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5
Q

What are the types of retinoids? how do they differ?

A

Preformed vitamin A and provitamin A carotenoids

Preformed sources include animals; provitamin sources include plants.

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6
Q

How is retinol transported in the circulation during fasted vs postprandial states?

A

Bound to retinol-binding protein (RBP) in fasting state/non-fasting state and packaged as retinyl esters in chylomicrons postprandially

RBP levels are often used as a proxy for retinol levels.

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7
Q

Where are retinoids stored in the body? how are they stored?

A

Stored as retinyl esters (retinyl palmitate) in hepatic stellate cells (HSCs) in the liver

HSCs store over 90% of total hepatic vitamin A, while only representing ~5% of cells in the liver

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8
Q

What are common ester forms of stored retinoids?

A

Retinyl palmitate (major), retinyl linoleate, retinyl oleate, retinyl stearate

These serve for long-term storage of vitamin A.

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9
Q

What is the role of 11-cis-retinal?

A

It is an active metabolite that is crucial for vision, acts as a chromophore in rhodopsin

Converts to all-trans-retinal upon light exposure.

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10
Q

What is all-trans-retinoic acid’s function?

A

Regulates gene expression by binding to nuclear receptors

It is not involved in vision and its synthesis is tightly regulated.

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11
Q

What is the importance of various metabolic forms of vit A? explain the metabolic pathway for excretion

A

Metabolic intermediated or breakdown products are essential to regulate excretion

Retinol → Retinal → Retinoic acid → hydroxylation → glucuronidation

Non-active metabolites serve no functional role but are crucial for homeostasis.

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12
Q

What is a Retinol Activity Equivalent (RAE)? what is the the conversion for b-carotene and other provitamin carotenoids?

A

A standardization of vitamin A activity from multiple sources

1:12 ug for b-carotene
1:24 ug for other carotenoids

1 µg retinol = 1 RAE, 12 µg β-carotene = 1 RAE, 24 µg other carotenoids = 1 RAE.

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13
Q

What are common trends for Vit A in terms of RDA? what is the RDA for men vs women >19yr old?

A

1) men have&raquo_space; RDA than women
2) increased requirements during pregnancy and lactation to account for fetal growth and breast milk production

900 ug for men and 700 ug for women

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14
Q

What are the dietary sources of vitamin A? what foods should be eaten to meet vit A requirements?

A

Animal sources provide preformed vitamin A; plant sources provide provitamin A carotenoids
- a balanced diet should provide ample amounts of Vit A

Examples include liver, dairy, carrots, and spinach.

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15
Q

Fill in the blank: Approximately ____ of vitamin A intake comes from preformed sources and ____ from provitamin sources

A

2/3 and 1/3

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16
Q

what ways can Vit A status be assessed?

A

symptoms, circulating retinol, and tracer studies

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17
Q

Are circulating levels of retinol an accurate assessment of Vit A status?

A

Circulating levels do not always correlate with hepatic Vit A levels because the liver secretes retinol at a steady state
-circulating levels are able to be maintained until the liver is almost completely empty of its Vit A stores

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18
Q

Why aren’t liver biopsys done to assess vit A status? what can be used instead?

A

They are unethical and impractical

A multi-compartment model is used to reflect stores in the liver
-uses a tracer (labelled retinoid) and analyzes isotope dilution

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19
Q

What are the two major forms of dietary Vitamin A? where are they found?

A

Preformed Vitamin A
-Retinol, retinal, retinoic acid
Provitamin A
-Beta-carotene

Retinol is found in animal sources, while beta-carotene is found in plant sources.

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20
Q

What are the key processes involved in Preformed Vitamin A absorption?

A

1) hydrolysis
2) uptake into enterocytes
3) esterification and chylomicron packaging
4) secretion of chylomicrons

comparable process to other lipid absorption

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21
Q

What enzymes are involved in the absorption of retinyl esters? how do they work? what type of Vit A is this? how does this differ from provitamin A absoprtion?

A

1) REH (Retinyl Ester Hydrolase; hydrolyzes retinyl esters into free retinol)
2) LRAT (Lecithin:retinol acyltransferase which transfers an acyl group to retinol to aid in packaging it into chylomicrons)

Retinyl esters are preformed Vit A sources, this differs from provitamin A absorption due to the need to be hydrolysed prior to entorocyte absorption

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22
Q

How is provitamin A absorbed? what enzymes are involved? what is their function?

A

Uptake into enterocytes, esterification and chylomicron packaging + secretion

1) CMO (carotenoid cleavage enzyme)
2) LRAT (lecithin:retinol acyltransferase; reduces retinol to retinol ester to be packaged into chylomicrons)

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23
Q

What is the role of the liver in Vitamin A metabolism? what percentage of retinyl esters are taken up by the liver?

A

The liver stores Vitamin A and regulates its supply to the body

About 75% of retinyl esters from chylomicrons are taken up by the liver.

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24
Q

what is the role of hepatocytes and stellate cells? where are they loctaed?

A

hepatocytes:
1) upatke of chylomicron retinyl ester
2) secretion of retinol into circulation

stellate cells: store Vit A in the liver as retinyl ester in lipid droplets

Both cells are found in the liver

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25
What is the function of retinol binding protein (RBP)? how does it differ from CRBP? where are each found?
Found in the blood; It transports retinol from the liver to tissues CRBP (cellular retinol binding protein) is located within the cells bound to retinol -it regulates the metabolic fate of retinol within the cell (hands to LRAT for esterification or RDH for retinal formation)
26
explain how hepatic uptake for chylomicron retinyl ester occurs. what receptors are involved?
the chylomicron reminant is taken up by LDL-receptor and bound to CRBP (cellular retinol binding protein)
27
How does CRBP regulate the storage of retinol? explain storage vs circulation of retinol
The Retinol:CRBP complex is transferred from hepatocytes to stellate cells where they are stored -LRAT converts the Retinol:CRBP complex to retinyl ester for storage in the lipid droplets of hepatic stellate cells When the retinyl ester is needed in circulation it is converted into free retinol by REH -the free retinol is shuttled back to hepatocytes where it binds to RBP for circulation to tissues
28
What are the active metabolites of Vitamin A? how does their function differ?
11-cis-retinal and all-trans-retinoic acid ## Footnote 11-cis-retinal is critical for vision, while all-trans-retinoic acid regulates gene expression.
29
What is the visual cycle and how is vitamin A involved? why is this important?
The visual cycle regenerates 11-cis-retinal, the form of vitamin A that binds to opsin to form rhodopsin (light-sensitive pigment). When light hits rhodopsin: 11-cis-retinal → all-trans-retinal (photoisomerization) All-trans-retinal is recycled back to 11-cis-retinal in the retinal pigment epithelium (RPE) This cycle enables continuous vision in low light.
30
How is all-trans retinoic acid metobolised? what enzymes are involved? what transported is responsible for uptake?
Retinol ↓ (via Retinol Dehydrogenase — RDH) Retinal (all-trans-retinal) ↓ (via Retinal Dehydrogenase — RALDH) All-trans-retinoic acid (atRA) -Stra6 is responsible for upatke into the cell ## Footnote Tightly regulated reactions
31
What 2 pathways can retinoic acid take? what is the purpose of this?
1) transcriptional activity in the nucleus 2) hydroxy metabolites through Cyp26 enzyme
32
Which proteins bind to retinoic acid in cells? what is their function?
CRABP (Cellular Retinoic Acid Binding Protein) and CRBP (Cellular Retinol Binding Protein) ## Footnote These proteins aid in solubility and trafficking of retinoids within cells.
33
What major systems in the body are affected by retinoid signaling?
Regulation of > 500 genes Immune system, Reproductive system (spermatogenesis), Skin and epithelial tissues, Nervous system, Cardiovascular system ## Footnote These systems rely on signals modulated by retinoic acid for differentiation and proliferation.
34
What is the role of CYP26 enzymes in retinoic acid metabolism?
They hydroxylate and catabolize retinoic acid into inactive polar metabolites ## Footnote This process helps maintain homeostasis and prevents toxicity.
35
what is phototransduction? what is the importance of this?
the isomerization between 11-cis retinal and all-trans retinal -when struck by light, isomerization occurs which allows us to see light
36
what types of nuclear receptors are there for retinoic acid?
1) 3 Retinoic Acid Recpetors (RAR)- a,b,y -ligand is all-trans retinoic acid 2) 3 Retinoid X Receptors (RXR)-a,b,y -controversial physiological relevance they work together to regulate transcription genes in repsonse to retinoic acid levels
37
Describe the mechanism of gene repression by retinoic acid.
In absence of retinoic acid, RAR:RXR dimers bind RAREs and recruit co-repressors, leading to chromatin compaction -histone deacetylation -> gene repression -genetic material unavailable for transcription ## Footnote This prevents gene transcription until retinoic acid is present.
38
Describe the mechanism of gene activation by retinoic acid.
Retinoic acid binds RAR:RXR dimers, recruiting co-activators, leading to histone acetylation and transcription initiation -unwinding of DNA to make it availble for gene transcription ## Footnote This process is specific, fast, and reversible.
39
what are the 2 retinoic acid target receptors? what is their function? why is it important to have both of these?
LRAT: forms retinyl esters for storage of retinol -lowers the amount of retinoic acid availible for metbaolites or nuclear signaling CYP26a1: converts retinoic acid into polar metabolites ## Footnote Shuttling of retinoic acid allows for tight regulation of it
40
What is the role of CYP26A1?
Hydroxylates and degrades excess retinoic acid ## Footnote This prevents toxicity and regulates Vitamin A levels.
41
True or False: Retinoic acid is stored in the body.
False ## Footnote Retinoic acid must be synthesized as needed.
42
What is the U-shaped effect of vitamin A?
Deficiency causes morbidity and mortality, while toxicity causes damage to organs and tissues -too much or too little will have negative impacts
43
Where is Vitamin A Deficiency (VAD) prevalent? what are causes of it?
VAD is rare in developed countries but widespread in developing countries -caused by malnutrition, fad diets, and conditions impacting lipid absorption
44
What are common causes of Vitamin A Deficiency in developed countries?
Restrictive diets, fat malabsorption, or clinical conditions
45
What is one sign of Vitamin A Deficiency related to vision? how does this occur? what impacts does this have on health?
Night blindness (nyctalopia) due to 11-cis-retinal deficiency -ocular defects
46
What systemic effects are caused by Vitamin A Deficiency?
Impaired immunity, impaired growth, congenital defects.
47
What is Xerophthalmia and what causes it? what occurs in severe cases?
Ocular lesions due to retinoic acid deficiency -causes damages to cornea and epithelial integrity -severe deficiency leads to hardening/scarring of the cornea (keratinization)
48
List the stages of Xerophthalmia according to WHO classification.
* XN – Night blindness (reversible) * X1A – Conjunctival xerosis (dryness) (reversible) * X1B – Bitot’s spots (foamy keratin plaques) (reversible) * X2 – Corneal xerosis (can be blinding) * X3 – Corneal ulceration (blinding)
49
What correlation exists between the severity of ocular lesions and mortality risk? why?
More severe eye lesions correlate with greater risk of death -It leads to reduced epithelial barrier (risk of UTI and respiratory issues) and weakened immune response.
50
What infections are associated with high mortality due to Vitamin A Deficiency?
* Pneumonia * Malaria * Measles * Diarrhea
51
What congenital birth defects are associated with Vitamin A Deficiency?
Evidence is weaker in humans, but VAD during pregnancy may impact fetal development.
52
What are the two main prevention strategies for Vitamin A Deficiency according to WHO? what do they include?
* Short-term: Supplementation -coupled with immunization * Long-term: Promotion of vitamin A-rich foods and fortification of staple crops -limited by regional availibility, seasonality and expense
53
What is fortification and give an example? why might this not be effective? what else can be done if fortification is not effective?
fortification is enhancing crops with nutrients, e.g., golden rice with beta-carotene -some populations are less likely to eat certain food groups (rice) , making fortification of this crop less useful Genetic engeneering of corn to make orange maize can be more beneficial for countries consuming more corn -controversial due to modification
54
What are some causes of Vitamin A Deficiency in the developed world?
* Fad diets * Unbalanced / bland diets * Food allergies * Autism-related food aversions * Fat-malabsorption disorders * Post-bariatric surgery
55
What are the 3 categories of Vitamin A Toxicity? How are they caused?
1) Acute toxicity caused by a single high dose of Vit A (>200 000 IU) -ie. polar bear liver 2) Chronic toxicity through long term consumption of high amounts of Vit A (25 000 IU) -typically through supplementation 3) Teragenicity: excess consumption during pregnancy (>10 000IU) typically from prescriptions, supplementation or accutane
56
What are symptoms of acute Vitamin A toxicity?
* Nausea * Vomiting * Blurred vision * Headache * Dizziness * Poor muscle coordination
57
What are symptoms of chronic Vitamin A toxicity?
* Liver damage * Intracranial pressure * Hair loss * Bone pain * Hypercalcemia * Dry, peeling skin * Orange skin * Birth defects (if in pregnancy)
58
What are risks of teratogenicity?
Increased rate of miscarriage or multiple abnormalities
59
What are common uses of retinoic acid as a therapeutic? why might it not always be effective?
retinoic acid regulates > 500 genes and is a common target for drugs 1) Cosmetics: increases collagen expression, changes skin epithelium -> firmer skin 2) Topical cream (acutane): retinoic acid agonist -> reduces sebum production 3) Differentiation therapy for acute promyelocytic leukemia (APL) 4) Male contraception: retinoic acid needed for spermatogenesis Retinoic acid has off target effects and may not be fully effective for treatments in all cases
60
What impact does cessation of Vit A consumption have on toxic effects?
Can reverse toxic effects -supplementation may reverse deficiency symptoms