Question

What is the active form of vitamin D, and how is it synthesized in humans?

Short answer

Answer: The active form of vitamin D in humans is calcitriol, which is chemically known as 1,25-dihydroxycholecalciferol or 1,25-(OH)2D3. The synthesis of calcitriol involves a series of reactions involving the skin, liver, and kidneys. Sunlight exposure triggers the conversion of 7-dehydrocholesterol into cholecalciferol, which is then converted to calcifediol in the liver and finally to calcitriol, the active form, in the kidneys.

Step-by-step solution

Active form of vitamin D

The active form of vitamin D in humans is called calcitriol, which is chemically known as 1,25-dihydroxycholecalciferol or 1,25-(OH)2D3.

Synthesis of Vitamin D in Humans

Vitamin D synthesis in humans occurs in a series of stages involving different organs, sunlight exposure, and chemical reactions. Here are the steps involved in the synthesis of the active form of vitamin D:

Sunlight exposure

The process begins with ultraviolet B (UVB) radiation from the sun converting 7-dehydrocholesterol, a compound found in the skin, into previtamin D3. Previtamin D3 then undergoes a heat-dependent process called isomerization, forming cholecalciferol, also known as vitamin D3.

Liver conversion

Vitamin D3 is released into the bloodstream and transported to the liver. In the liver, a hydroxyl group is added to carbon 25 of the cholecalciferol molecule by hydroxylase enzyme, resulting in the formation of calcifediol, or 25-hydroxycholecalciferol (25-OH-D3).

Kidney conversion

Calcifediol (25-OH-D3) is then transported to the kidneys, where another hydroxyl group is added to carbon 1 of the molecule by the enzyme 1α-hydroxylase. This process transforms calcifediol into calcitriol, the active form of vitamin D (1,25-dihydroxycholecalciferol or 1,25-(OH)2D3).

Summary

The active form of vitamin D in humans is calcitriol, and it is synthesized through a series of reactions involving the skin, liver, and kidneys. Sunlight exposure triggers the conversion of 7-dehydrocholesterol into cholecalciferol, which is then converted to calcifediol in the liver and finally to calcitriol, the active form, in the kidneys.

Key concepts

Calcitriol

Calcitriol, scientifically known as 1,25-dihydroxycholecalciferol or 1,25-(OH)₂D₃, is the most active form of vitamin D in the human body. Playing a crucial role in managing calcium and phosphorus levels, it aids in maintaining healthy bones and teeth. Unlike other vitamins which are obtained solely through diet, calcitriol is produced internally after a process that starts when our skin is exposed to sunlight.

Once formed, calcitriol binds to receptors in various organs, essentially acting as a hormone. It is critical in the absorption of calcium from the diet, helping to regulate the concentration of calcium in the blood. Without sufficient levels of calcitriol, the body would struggle to maintain the mineral balance necessary for bone formation and maintenance.

Vitamin D Metabolism

Vitamin D metabolism is a complex process involving multiple organs and enzymatic reactions, collectively known as vitamin D hydroxylation. The process starts in the skin where a form of cholesterol, 7-dehydrocholesterol, is transformed into vitamin D3 (cholecalciferol) under the influence of sunlight's UVB rays. Vitamin D can also be obtained from dietary sources and supplements.

Once synthesized or ingested, vitamin D3 travels to the liver, where it is hydroxylated to form calcifediol (25-hydroxycholecalciferol). This substance is then transported to the kidneys, where a second hydroxylation occurs, producing calcitriol. The precise regulation of these processes ensures that the level of active vitamin D remains within a range that is beneficial to the body, avoiding the adverse effects of either deficiency or excess.

UVB Radiation and Vitamin D

The role of ultraviolet B (UVB) radiation in vitamin D synthesis is foundational. Upon exposure to UVB rays from the sun, compounds in our skin's cells known as 7-dehydrocholesterol absorb the energy and are converted into previtamin D3. This substance undergoes a temperature-dependent transformation to become vitamin D3, also known as cholecalciferol.

It's important to note that factors like geographic location, skin pigmentation, and sunscreen use can affect UVB radiation absorption and, subsequently, vitamin D synthesis. Therefore, in some cases, it might be necessary to supplement vitamin D, especially in regions with less sunlight exposure or for individuals with limited outdoor activities.

Hydroxylation Reactions in Vitamin D Synthesis

Hydroxylation reactions are chemical processes critical in the synthesis of active vitamin D. These reactions involve the addition of a hydroxyl group (-OH) to the vitamin D molecule, a modification that significantly alters its biological activity.

The first hydroxylation occurs in the liver, where vitamin D3 (cholecalciferol) is converted into calcifediol (25-hydroxycholecalciferol) by the enzyme 25-hydroxylase. This form is the primary circulating metabolite and is often measured to assess vitamin D status. The second and final hydroxylation takes place in the kidneys, catalyzed by the enzyme 1α-hydroxylase, which converts calcifediol to calcitriol (1,25-dihydroxycholecalciferol), the biologically active form of vitamin D.