Fat soluble Vits & vitamin A (mine)

fat soluble vits dissolve in 

organic solvent 

fat soluble vits excretion

not readily excreted, can cause toxicity

fat soluble vits are absorbed with

along with fat

there is concern for what with fat soluble vits 

Concern for people with fat malabsorption or use of certain medication (e.g. orlistat or Xenical)

transportation of fat soluble vits occurs how

like fat in chylomicrons, VLDL, LDL

Transportation for fat soluble takes place in...

lymphatic system w/ bile

VIT A

Vitamin A is the most common cause of....

non-accidental blindness, worldwide

Preformed Vitamin A forms are called

retinoids

retinoids are what form of vit A

active form (ready to use)

retinoids are found in

found in animal products

Retinoid forms****

retinal

retinol

retinoic acid

aldehyde form of vit A

Retinal

proformed forms of vitamin A are called

carotenoids

what must occur to proformed vit A (carotenoids)

must be converted to retinoid form

intestinal cells can do what to carotene?

intestinal cells split carotene in 2 molecules of retinoids

carotenoids are found in

plant products

carotenoids forms

beta-carotene

alpha-carotene

lutein

lycopene

zeaxanthin

what carotene form is largely the form received from diet

beta-carotene

antioxidant function of “vit A” is related to

carotenoids!! so it is not actually vit A function because carotenoids are not Vit A until they are converted into retinoids

Digestion of VitA requires...

digestion prior to absorption

what can weaken some complexes

heating plant food

even with weakening complexes of plant foods, what is still needed?

enzymatic digestion is still required

how well is vit A absorbed

• from meal with fat

• raw veg

• pure oil

- 70-90% vit A absorbed from meal (w/ fat)

- carotenoid absorption is <5% for uncooked vegs

-60% as pure oil

retinoids are most commonly found in what form

all-trans form

retinoids tend to be attached to what

a fatty acid 

since it retinoids tend to be attached to FA, what must occur prior to absorption?

they must be de-esterified (remove the FA)

when retinoids are going to be stored, what happens to them

they are reesterified 

what are retinyl esters?

esterified retinoids (so retinal, retinol, or retinoic acid attached to FA)

why do we need proteolytic enzymes in the duodenum (2)

• retinol bound to fatty acid esters

• retinyl esters and carotenes are often complexed with protein 

What enzymes hydrolyze long chain retinyl esters in the brush border? (2)

Retinyl ester hydrolases and esterases

What is the role of pancreatic hydrolases in vitamin A digestion?

They cleave short chain retinyl esters.

What process is involved in the digestion of fat globules?

Emulsification

retinol absorption in the body is dependent on

protein carrier

What transporters are involved in the absorption of carotenoids?

Scavenger receptor class B type 1 (SR-B1) and passive diffusion

absorption of vit A requires what? (3- think digestive system)

bile, digestive enzymes, integration into micelles

absorption of vit A is depended on what from the diet?

fat

How much of retinoids can be absorbed?

90%

How much of carotenoids can be absorbed?

5%

how much beta-carotene can be absorbed?

20-50% (higher)

intestinal cells can convert what into what relating to vit A?

carotenoids to retinoids

Where are carotenoids & retinoids metabolized

in enterocytes to some extent

To leave the intestinal cell and travel to other tissues in the body, retinol must be

esterified

once retinol is esterified, it can

it can be incorporated into chylomicrons

the main metabolic pathway for retinol depends on what protein?

Cellular retinol-binding protein (CRBP)

Conversion of carotenoids is dependent on...

vit A status of person & intake of carotenoids

Higher intake of Vit A ___ receptor mediated carotenoid absorption & conversion to vit A is ____

decreases

decreased

What non central enzyme converts carotenoids in the intestine?

9,10 dioxygenase

What central enzyme hydrolyzes carotenoids in the intestine and other organs?

15,15 monooxygenase (fe dependent)

15,15 monooxygenase is dependent on

iron 

Conversion to retinal is ___% efficient

50%

CRBP transports in ____

tissue

RBP transports in ____

blood

B-carotene is converted into what when absorbed into intestinal cell?

two retinal molecules

how is b-carotenoid converted into retinal? (enzyme)

15,15 carotenoid monooxygenase will split b-carotene into 2 retinal molecules 

free Carotene enters intestinal cell how?

absorption by scavenger receptor class B type 1 (SR-B1) on the brush border membrane

beta carotene and retinol enter intestinal cell from what structure?

micelle 

b-carotene is converted into what?

2 retinal molecules via 15,15 carotenoid monooxygenase

retinal can undergo what 2 different paths?

can be converted into retinoic acid to go into the blood OR can be esterified to go into chylomicron and enter lymphatic system 

what is unique about retinoid acid?

it can enter directly into the blood to go to the liver (does not need to go through lymphatic system)

what binds to both retinol & retinal in the intestinal cell

CRBP II (cellular retinol binding protein)

what is formed when CRPBII attached to retinal

CRBPII-retinal

CRBPII-retinal is then needed to be converted into

CRBPII-retinol

how is CRBPII-retinal converted to CRBPII-retinol? (enzyme)

via retinal/retinaldehyde reductase to form CRBPII-retinol

retinal-CRPBII —> CRBPII-retinol

when retinol has CRBPII added to it, it becomes?

CRBPII-retinol 

what happens to CRBPII-retinol? 

it has a FA added to it to form CRBPII-retinylpalmitate 

what enzymes esterifies a FA (palmitic acid) to form CRBPII-retinylpalmitate 

lecitin retinol acyl tranferase (LRAT)

so LRAT is the enzyme that esterifies retinol 

what are retinyl esters?

FA esterified by adding CRPBII-retinol 

Retinyl esters (retinal + FA) are incorporated what compounds to form what?

phospholipids, TG, Chol esters, carotenoid & apoproteins to form chylomicron

what happens to chylomicrons

they enter the lymph system and then ultimately the blood

what happens to carotenoids that enter intestinal cell but not going to be used as Vit A

enter intestinal cell and are directly incorporated into chylomicrons 

is conversion of retinal to retinol reversible?

yes

How is retinal —> retinol (enzyme and coenzyme)

retinal reductase (NADH)

how is retinol—> retinal? (enzyme, coenzyme)

retinal dehydrogenase (NADPH/ NADH)

is conversion of retinal to retinoic acid reversible?

no

retinal to retinoic acid (enzyme, coenzyme)

retinal oxidase (NAD or FAD)

9-cis retinoic acid comes from what retinoid?

all-cis-retinol

9-cis retinoic acid plays a role in?

gene expression

4-oxoretinoic acid comes from what retinoid?

retinoic acid in blood 

4-oxoretinoic acid role?

cell cycle, cell growth

what forms of Vit A enters the liver?

retinyl esters are taken into the liver cells 

retinyl esters that enter liver can come from what 2 things?

stellate cells or chylomicrons

what happens once retinyl esters enter the cell 

the retinol and FA are released

what enzyme releases FA’s and retinyl esters?

retinyl ester hydrolase

retinol entering the liver can go to what 2 paths?

storage or metabolism 

if retinol will go into storage (hepatic stellate cells), it must be converted into 

back into retinyl esters

how can retinol go back to retinyl esters (2 options)

can be esterified via ARAT to form retinyl esters 

OR

can bind to CRBP 1 to form RCBP-retinol in order to be esterified by LRAT to form retinyl esters 

if going to be used for metabolism, retinol will

remail unesterified

what form of retinol is used for metabolism (that will then be converted to other forms)

CRBP-retinol 

If going to leave the liver cell, CRBP-retinol will bind to 

retinal binding protein (RBP)

CRBP-retinol binding to RBP forms

holo-retinol-RBP

CRPB-retinol to holo-retinol-RBP how?

CRBP-retinol —→ holo-retinol-RBP by adding retinol-binding protein (RBP)

holo-retinol-RBP goes where?

enters the blood (plasma)

to travel in the blood, holo-retinol-RBP has what added to it? (2)

transthyretin (TTR) and thyroxin (T4) to become trimolecular complex

by adding transthyretin (TTR) and thyroxin (T4) to holo-retinol-RBP, it forms

trimolecular complex

retinol that is esterified may be stored in the ___ via ____ cells

liver

stellate and parenchymal cells

Proteins that transport via the blood (2)

Retinol-binding protein (RBP)

Transthyretin (TTR)

Carotenoids transported as part of ___ & stored in ___ & ___

lipoproteins

liver & adipose

what are the 2 major receptors associated with vit A

Retinoic acid receptor (RAR) & retinoid X receptor (RXR)

Retinoic acid receptor (RAR) & retinoid X receptor (RXR) found on the ___

nucleus