Vitamin A: Color Detection, Visual Cycle and Retinoic Acid Function

00:01 So the process that I’ve just described to you for the transmission of information from the eye cell to the brain is known pretty much for the rod cells.

00:09 Less is known about how the process occurs in the cone cells but it is believed to happen in a pretty much the same way as in the rod cells.

00:16 Now, as I said earlier, the cone cells have pigments that have varying sensitivity to different wavelengths of light.

00:23 Cone cells need direct light and they need direct strong light in order to detect the colors that they detect.

00:30 Cone cells as I said need more intense light.

00:32 What would stimulate rod cell might not stimulate a cone cell.

00:37 The detection process as I said, however, is pretty much the same.

00:41 Now, the cone cells that have various maxima in the red region, for example, are more likely to fire if they get red light shined upon them whereas those that have maxima in the green, they get fire when the get green and those in the blue more likely when they get blue.

00:57 The colors detected by the cone cells and by the brain, not by the sensitivity of any individual cells, but rather by a polling of groups of cells.

01:06 So a group of blue cone cells in one cluster that all send a signal to the brain about blue color then tell the brain, “Yes, we really did get a blue color and that wasn’t an aberrant signal that we got.

01:17 The brain then paints that image that we see as a result of these actions of these individual cells.

01:24 Now, after vitamin A has been isomerized from the 11-cis to the trans form, it has to reconverted back to the 11-cis form.

01:32 Now, I told you that light can cause that interconversion to occur that is it can go from cis to trans and trans to cis.

01:38 But it turns out that that’s not what the cell does to get the trans form back.

01:43 And it turns out, it’s kind of a complicated process.

01:45 The process is known as the visual cycle.

01:48 And I’m going to describe it to you here.

01:50 So first we have the absorption of a photon that causes the 11-cis to move out to the all-trans form and that all-trans form of retinal now is converted back into the 11-cis form in this visual cycle that I’m going to describe to you.

02:04 The all-trans retinal now first of all is released after it has been converted into the all-trans form That release happens in the figure that you can see in the lower right.

02:15 So after the all-trans retinal form has been formed, it has to be converted back to the 11-cis form and that process is kind of complicated.

02:24 First of all, the retinal all-trans form is reduced to retinol to make the all-trans retinol form.

02:31 The all-trans retinol is esterified to a fatty acid as I have shown before and then that esterified retinol fatty acid form is converted back to the 11-cis form by an enzyme known as retinol isomerase.

02:46 Now, the retinol isomerase then releases the 11-cis form of retinol.

02:52 The fatty acid is cleaved off and the aldehyde, the alcohol, is oxidized back to an alcohol.

02:58 So there’s a lot of chemistry that’s going on to recreate that 11-cis retinal so that another cycle of vision can occur.

03:06 The 11-cis retinal after it’s been formed by this process that I’ve just described to you is then linked to the opsin and cause the formation of rhodopsin in the case of rod cells or photopsin as in the case of cone cells.

03:21 Now, another form of vitamin A is retinoic acid.

03:23 And it has a function that’s completely different from that in vision.

03:27 First of all, the retinoic acid is created from the retinal by an oxidation reaction.

03:34 This oxidation reaction that creates retinoic acid is non-reversible.

03:38 That is we can’t make retinoic acid back into retinal.

03:42 So it’s for this reason we call it a nonstorage form of vitamin A.

03:47 The intracellular signalling system in the embryo uses retinoic acid as a way to determine the anterior and posterior region of the embryo for the development through Hox genes.

03:57 Hox genes play very important roles during the development of organisms that have many different limbs and features as we do.

04:07 Retinoic acid is therefore strongly teratogenic, meaning it strongly favors differentiation.

04:13 So retinoic acid exerts its functions through a retinoic acid receptor known as RAR or the retinoic X receptor known as RXR.

04:22 These receptors allow the cell to activate the transcription of genes that are known as rare genes.

04:29 And I’ll describe those in just a moment.

04:31 So as I said, retinoic acid acts through RAR, and RAR is a transcription factor, meaning it’s a protein that will bind to DNA and activate certain genes.

04:43 The sequence that RAR binds to is known as rare, R-A-R-E, or retinoic acid response element.

04:51 RARE genes are genes that are involved in the process of development and it’s for this reason that retinoic acid is so strongly teratogenic.

05:00 The retinoic acid response element control genes involved in differentiation.

05:05 As I said earlier, Hox genes that are involved in controlling differentiation of organisms, that are like we are, are regulated ultimately by retinoic acid.

05:17 RARE sequence.

05:18 This retinoic acid response element, as I said, are sequences located upstream of genes that control differentiation.

05:25 Now, some of these genes are involved in the Hox gene transcription as retinoic acid is involved in controlling them.

05:31 These are regulated by retinoic acid acting through the RAR binding to these RARE sequences as we see here.

05:39 Now, because retinoic acid is so strongly teratogenic and causing differentiation, that’s one way to treat cancer.

05:45 And so there are derivatives of vitamin A known as isotretinoin or allretinoin as you can see on the screen here that are used to treat cancer and in some cases to treat acne because they actually have pretty strong effects on the skin.