Reading Notes

OK, so I was curious about how human digestion works. As I was eating an olive in a huge salad, the question came to my mind: 'if vitamins are such a small yet essential portion of our diet, how does the body sort out these tiny dosages and get them to the places they are needed?'

Fats, carbohydrates, and proteins comprise the main bulk of our diet and it seems reasonable the body has a bulk process that moves these sources of energy around. But how do we make sure the needle in haystack vitamins go through special delivery mail, and not the bulk correspondence with utility bills, credit card statements, and the junk mail?

So I found this book that more or less answers my question on physiology.

The Vitamins: Fundamental Aspects in Nutrition and Health by Gerald F. Combs, Jr.

Vitamin A - all trans retinol

I more or less learned how it works for Vitamin A. In imprecise terms, I think it goes like this. Vitamin A is broken down into a basic form during digestion, re-uptaked by specialized enzymes at the intestine into a compound form suitable for humans, sent swimming along the blood/lymphatic system, deposited in the liver organ for storage, converted into a delivery compound and dispersed uniformly throughout the bloodstream to be taken by whichever cells grab it as it swims by. I assume other vitamins go through different but similar pathways.

"I have found it to be true that one learns best what one has to teach. And, because I have no formal training either in teaching or in the field of education in general, it was not for several years of my own teaching that I began to realize the good teacher must understand more than the subject matter of his or her course. In my case, that realization developed, over a few years, with the recognition that individuals learn in different ways and that the process of learning itself is as relevant to my teaching as the material I present.

...

"I have come to understand that people think (and, therefore, learn) in terms of concepts - not facts."

Vitamin

organic compound, naturally found in foods in small amounts, not belonging to the categories of fats, carbohydrates, and proteins, that are essential for normal physiological function and cannot be synthesized by the host (vitamin D an exception).

vitamin vs hormone, basically hormones are routinely produced by the body and vitamins have to come from dietary intake.

Vitamin C can be produced by most animal species. Ascorbic acid it's called. Guinea pigs and humans lack an enzyme I-gulonolactone oxidase and cannot produce ascorbic acid, so for us it's a vitamin. Technically, it's not for those that can create it themselves.

is cholecalciferol same thing as vitamin D? it's one of the five forms of Vitamin D. can be produced with modest exposure to sunlight, then functions as a hormone.

Choline is a vitamin for chick and rat, when they lack methyl-donor compounds in their diet, they can't produce it.

Niacin is nicotinic acid mononucleotide, synthesized from the amino acid tryptophan. Low tryptophan diets in cat, fishes cannot produce niacin.

fat-soluble vitamins DEAK

vitamin A is sensitive to oxygen, light and heat. (breaks down)

vitamin D is a steroid. sensitive to oxygen light and iodine.s

p62 'Only one stereoisomer occurs naturally: the R,R,R - form. The chemical synthesis of vitamin E produces mixtures of other stereoisomers, depending on the starting materials....

In recent years, however, the commercial synthesis of vitamin E has turned away from using iso-phytol in favor of a fully synthetic side-chain."

p123

"Most of the pre-formed vitamin A in the diet is in the form of retinyl esthers... retinyl esters are hydrolyzed to yield retinol by hydrolases produced from the pancreas."

So guys that break stuff down come out of the pancreas, go into the stomach with the vitamin A (retinol) pro-vitamins (stuff that gets turned into retinol) from food, break that shit down into retinol.

"Overall absorption of vitamin A esters appears to be high (e.g., 80-90%), but this process is necessarily affected by the level and type of dietary fat and protein (which exerts surfactant effects)"

I think what this is saying, is vitamin A esthers are hydrophobic so they need some fat molecules to cling to, so they don't get washed out with the rest of the poop.

"Retinol, formed either from the hydrolysis of dietary retinyl esters or from the reduction of retinal cleaved from Beta-carotene, is quickly re-esterified with long-chain fatty acids in the intenstinal mucosa."

Right after enzymes break down retinol out of the food, the retinol gets turned back into a retinyl ester that the human body uses. (I'm assuming esters for each biological creature are different, so that's why the human body creates its own. And it's computationally time efficient to just assume everythang is foreign and break it all down, build it back up, than to check individually if the ester eaten is compatible to humans)

"Vitamin A is transported to the liver mainly (i.e., 80-90% of a retinol dose) in the form of reinyl esters."

Why does it go to the liver, what happens after it gets there, buys a summer home and raises a family.

"The composition of lymph reinyl esters is remarkably independent of the fatty acid composition of the most recent meal. Retinyl palmitate typically comprises about one-half o fthe total esters, with reinyl stearate comprising about one-quarter and retinyl oleate and retinyl linoleate being present in small amounts."

How the retinol gets turned back into ester by the body:

"Two pathways for the enzymatic re-esterification of retinol have been identified in the microsomal fraction of the intestinal muscosa. The first, a high-affinity route, involves retinol complexed with a specific binding protein, cellular retinol-binding protein (type II); it is catalyzed by lecithin:retinol acyl-transferase (LRAT). The second, a low-affinity route, involves retinol apparently bound non-specifically to cellular proteins; it is catalyzed by acyl co-enzyme A: retinol acyl-transferase (ARAT)."

(http://life.gaiam.com/article/6-ways-boost-circulation-detoxing-and-immunity

"Rebounding (jumping on a trampoline) appears to be especially effective at improving lymph system circulation. Lymphatic fluid is completely dependent on physical exercise to move, and the up-and-down rhythmic gravitational force caused by jumping on a trampoline causes the lymph system’s one-way valves to open and close, increasing lymph flow.")

"Retinyl esters are secreted from the intestinal mucosal cells in the hydrophobic cores of chylomicron particles by way of which absorbed vitamin A is transported to the liver through the lymphatic circulation, ultimately entering the plasma compartment through the thoracic duct."

Does the retinol circulate in the blood stream before separating out into the lymph system, or is there a direct pathway? Does retinol go into the blood stream? Where does it go right after secretion from the intestine??

Chylomicro particles? What is? How doing? Why speaking? Plasma compartment? Thoracic duct?

portal absorption

"Studies have shown that vitamin A can also be absorbed via a non-lymphatic pathway. Rats with ligated thoracic ducts retain the ability to deposit retinyl esters in their livers. That such animals fed retinyl esters show greater concentrations of retinol in their portal blood than in their aortic blood suggests that, in mammals, the portal system may be an important alternative route of vitamin A absorption when the normal lymphatic pathway is blocked. This phenomenon corresponds to the route of vitamin A absorption in birds, fishes and reptiles which, lacking lymphatic drainage of the intestine, rely strictly upon portal absortpion."

I guess liver cuts it back down to retinol.

"Newly absorbed retinyl esters are taken up by the liver in association with chylomicron remnants by receptor-mediated endocytosis on the part of liver parenchymal cells. Within those cells, remnants are degraded by lysosomal enzymes. It appears that intact retinyl esters are taken up and are subsequently hydrolyzed to yield retinol."

"Retinol an be transferred from the parenchymal cells to stellate cells where it is re-esterified. It is likely that the re-esterification proceeds by a reaction similar to that of the intestinal microsomal acyl CoA:retinol acyltransferase (ARAT). The liver thus serves as the primary storage depot for vitamin A, normally containing more than 90% of the total amount of the vitamin in the body."

Goes to the liver to be stored and retrieved when needed.

How is the vitamin spread to the sites where it is needed?

"Vitamin A is mobilized as retinol from the liver by hydrolysis of hepatic retinyl esters. ... Once mobilized from liver stores, retinol is transported to peripheral tissues by means of a specific carrier protein, plasma retinol binding protein (RBP). Human RBP consists of a single polypeptide chain of 182 amino acid residues, with a molecular weight of 21 kD; it has a single binding site for retinol."

it's so cool that the protein is specific to just retinol. and it works cause that's the 'language' the body works in; it breaks everything down into retinol so the protein can work just with retinol.

"The secretion of RBP from the liver is regulated in part by estrogen levels, and by vitamin A status (i.e., liver vitamin A stores) protein, and Zn status; deficiencies of each markedly reduce RBP secretion and, thus, reduce circulating levels of retinol. In healthy human adults, plasma RBP is 40-50 ug/ml"

Oh it's just in the blood. So i guess anyone who wants some, takes it. If the liver banks are low in supply, then the amount in circulation is low too.

So it does matter if you don't get enough vitamin A daily, because if the liver supplies are low, there will be less in the blood - ya know, even though the body has enough to supply the need, it's gonna hold back because it doesn't want to go empty.

Why is retinol necessary? Which cells take up this stuff. What do they do with it.

"The retinol ligand of holo-RBP is taken into cells via specific receptor mediated binding of RBP. Apparently, RBP binding facilitates the release of retinol to the target cell; this is accompanied by an increase in the negative charge of apo-RBP which reduces its affinity for transthyretin, which is subsequently lost. ['In the plasma, RBP forms a 1:1 complex with transthyretin.'] The residual apo-RBP is filtered by the kidney where it is degraded." "The kidney appears to be the only site of the catabolism of RBP, which turns over rapidly."

cells bind RBP by specific sites. retinol goes inside. the remnants are apo-RBP. they get recycled in the kidneys.

Uses of retinol:

"The best elucidated function of vitamin A is in the visual process where, as 11-cis-retinal, it serves as the photosensitive chromophoric group of the visual pigments of rod and cone cells of the retina. Rod cells contain the pigment rhodopsin; cone cells contain one of three possible iodopsins. In each case, 11-cis-retinal is bound (via formation of a Schiff's base) to a specific lysyl residue of the respective protein (collectively referred to as "opsins").

The visual functions of rhodopsins and the iodopsins differ only with respect to their properties of light absorbency, which are conferred by the different opsins involved. In each, photo-reception is effected by the rapid, light-induced isomerization of 11-cis-retinal to the all-trans-form. That product present as a protonated Schiff base of a specific lysyl residue of the protein, produces a highly strained conformation. This results in the dissociation of the retinoid from the opsin complex. This process ("bleaching") is a complex series of reactions, involving progression of the pigment through a series of unstable intermediates of differing conformations and, ultimately, to N-retinylidene opsin which dissociates to all-trans-retinal and opsin.

The dissociation of the all-trans-retinal and opsin is coupled nervous stimulation of the vision centers of the brain. The bleaching of rhodopsin causes the closing of Na+ channels in the rod outer segment, thus, leading to hyperpolarization of the membrane. This change in membrane potential is transmitted as a nervous impulse along the optic neurons. This response appears to be stimulated by the reaction of an unstable "activated" form on rhodopsin, metarhodopsin II, which reacts with transducin, a membrane-bound G-protein of the rod outer segment discs. This results in the binding of the transducin alpha-subunit with cGMP phosphodieterase, which activates the latter to catalyze the hydrolysis of cGMP to GMP. Because cGMP maintains Na+ channel of hte rod plasma membrane in the open state, the resulting decrease in its concentration causes a marked reduction in Na+ influx. This results in hyperpolarization of the membrane and the generation of a nerve impulse through the synaptic terminal of the rod cell."

The visual process is a cyclic one, in that its constituents are regenerated. All-trans-retinal can be converted enzymatically in the dark back to the 1--cis form,. After bleaching, all-trans-retinal is rapidly reduced to all-trans-retinal, which is isomerized to the 11-cis form in the rod outer segment. Retinol is then transferred (presumably via IRBP) into the retinal pigment epithelial cells where it is esterified (again, predominantly with palmitic acid) and stored in the bulk lipid of those cells. The regeneration of rhodopsin, which occurs in the dark-adapted eye, involves the hydrolysis of retinyl esters to yield retinolw hich is transferred (probably via IRBP) into the rod outer segment where it is oxidized to 11-cis-retinal, which cna then react with an opsin-lysyl residue. Nervous recovery is effected by the GTPase activity of the transducin alpha-subunit which, by hydrolyzing GTP to GDP, causes the re-association of transducin subunits and, hence, the loss of its activating effect on cGMP phosphodiesterase. "

"Though they are much less well understood, the extra-retinal functions of vitamin A are clearly of greater physiological impact than the visual function."

Awwww maaaaan. The more important stuff is always harder to learn!

"Collectively, these are called the "systemic" functions of the vitamin; more specifically, they include roles int he differentiation and growth of epithelial cells and on growth in general. While deprivation of vitaminA disrupts the visual cycle resulting in impaired dark adaptation (night blindness, or nyctalopia), the disruption of the "systemic" functions of the vitamin are far more severe and often life-threatening (e.g., corneal destruction, infection, stunted growth).

"The oxidation of retinal to retinoic acid is irreversible, the retinoic acid can support only the systemic functions [Although retinol can be oxidized metabolically to retinal and, then, to retinoic acid,' both retinol and retinal can support systemic or visual process. The vision uses solely retinal.] Animals fed diets containing retinoic acid as the sole source of vitamin A grow normally and appear healthy in every way except that they go blind.

"Vitamin A has a clearly vital role in the differentiation of epithelial cells. It is well documented that vitamin A-deficient individuals (humans or animals) experience replacement of normal mucus-secreting cells by cells that produce keratin."

Wow that's craaaaazy. Vitamin A is like an identifier for what the cell is/does! So if you can't tell what is what, the body will merely substitute one indistinguishable cell for another! LOL, replace all my brain cells with like... penis cells. That's how you think with your Willie! Oh wait, epithelial cells. That doesn't include the brain. But maybe i can get a dickfore on my forehead.

"it has been proposed that vitamin A has a co-enzyme-like role as a sugar carrier in the synthesis of glycoproteins, which function on the surfaces of cells to effect intercellular adhesion, aggregation, recognition and other interactions."

Helps build other shit the body needs. By transporting sugar during construction of glycoproteins.

"Vitamin A is necessary for reproduction, but the biochemical basis of this function is not known. It is apparent, however, that this role is different from the "systemic" one, as maintenance of reproduction is discharged by retinol and not retinoic acid, at least in mammals. For example, rats maintained with retinoic acid grow well and appear healthy, but lose reproductive ability,

Hey waaaait a minute.. you just told me early that rats fed only retinoic acid were otherwise healthy except only they were blind. but now you're telling me they can't have babies either. Seems like you were leaving something out... and now the sterile rats you're saying are otherwise healthy, but you're not mentioning that they'd be blind too! What's the big idea!?

Although for practical reasons, unrelated to the biology it would make sense that the blind rats wouldn't be able to have children.

"Males show impaired spermatogenesis and females abort and resorb their fetuses. Injection of retinol into the testis restores spermatogenesis, indicating that vitamin A has a direct role in that organ."

Aaaand a bunch of other stuff: immune system identifying which cells are which helps produce more of the right disease killing cells apparently, helps create bone, might lead to cancers if deficient, and other stuff not really understood yet as of book 1992.

"Certain dermatologic disorders of keratinization (e.g., ichthyosis, Darier's disease, pityriasis, rubra pilaris) have been treated with large doses of vitamin A. Clinical success rates of such treatments generally appear to be variable, and the high doses of the vitamin needed for efficacy commonly produce unacceptable side effects."

LOL. they don't know what the shit is going on, it's clearly not the right answer vitamin A, but sometimes for some unknown and unconnected reasons, vitamin A could throw the body into a jumble and produce the desired results. It's like rolling dice, or slapping the Television to make it work. But you end up fucking up not just the skin disease, but everything else in the body too.