Introduction: A 2-year-old male named Justin. He is suffering from hypotonia (decreased muscle tone), weakness and growth failure, and is unable to walk. His mother has just brought him into the emergency room from the family beach house, where they have been spending the summer, because he has had a seizure. X-rays indicate that the toddler is suffering from rickets, which is a result of a nutritional deficiency of Vitamin D. But his mother insists that her son's diet is not Vitamin D-deficient. He drinks three glasses of milk a day, and his diet also includes meat and eggs.A simplified scheme of Vitamin D metabolism is shown in the figure attached. The chemical name of active Vitamin D is 1a, 25-dihydroxycholecalciferol, and it is synthesized via the pathway shown. Catalysts, both in the form of enzymes and ultraviolet light, are required for Vitamin D synthesis. The two main sources of active Vitamin D are diet and sunlight.Food supplemented with "Vitamin D" usually contains cholecalciferol (Vitamin D3). In the liver, dietary cholecalciferol is converted to 25-dihydroxycholecalciferol. Next, in the kidney, that chemical is converted to active Vitamin D.Sunlight is also responsible for producing Vitamin D. The skin contains a precursor, 7-dehydrocholesterol. In the presence of ultraviolet light, which acts as a catalyst, a ring-opening reaction occurs, which is followed by the spontaneous conversion of this intermediate to Vitamin D3, and this follows the dietary Vitamin D3 pathway to become active Vitamin D.Active Vitamin D is a steroid-like compound that acts in combination with other hormones to increase the concentration of Ca2+ via a variety of mechanisms, one of which includes increasing the intestinal absorption of dietary calcium (intestinal absorption of dietary phosphate, a calcium counter-ion, also increases as a result). Calcium ions are required to form hydroxyapatite Ca5(PO4)3OH, the main mineral constituent of bone.It is decided to carry out further analysis and take a sample of Justin's blood. The laboratory results are attached:A. After obtaining the results from the laboratory, it is suspected that the patient might have a defective enzyme in the Vitamin D synthetic pathway. Which enzyme is defective, and why? This table provides laboratory test results for a patient, comparing their values with established normal ranges.### Patient Laboratory Test Results| Test | Patient | Normal Range ||-----------------------------------------------------|---------|---------------|| **Serum Calcium, mg/dL** | 5.1 | 8.7-10.1 || **Serum Phosphorous, mg/dL** | 4.2 | 2.4-4.3 || **Serum 1α, 25-dihydroxycholecalciferol, pg/mL** | 13 | 20-76 || **Serum 25-hydroxycholecalciferol, ng/mL** | 48 | 10-55 |### Explanation of the Results- **Serum Calcium (mg/dL)**: - **Patient Value**: 5.1 - **Normal Range**: 8.7-10.1 - **Interpretation**: The patient's serum calcium level is significantly below the normal range, indicating possible hypocalcemia.- **Serum Phosphorous (mg/dL)**: - **Patient Value**: 4.2 - **Normal Range**: 2.4-4.3 - **Interpretation**: The patient's serum phosphorous level is within the normal range.- **Serum 1α, 25-dihydroxycholecalciferol (pg/mL)**: - **Patient Value**: 13 - **Normal Range**: 20-76 - **Interpretation**: The patient's level of 1α, 25-dihydroxycholecalciferol is below the normal range, which could suggest a deficiency in active vitamin D.- **Serum 25-hydroxycholecalciferol (ng/mL)**: - **Patient Value**: 48 - **Normal Range**: 10-55 - **Interpretation**: The patient's level of 25-hydroxycholecalciferol is within the normal range, indicating adequate storage level of vitamin D.### SummaryThe table highlights that the patient has notable deficiencies in serum calcium and 1α, 25-dihydroxycholecalciferol levels, ### Vitamin D3 Synthesis and Metabolism PathwayThis diagram outlines the synthesis and metabolism pathway of Vitamin D3, also known as cholecalciferol, highlighting the transformation at various stages under different conditions and enzymes. Here's a detailed explanation:1. **7-Dehydrocholesterol**: This is the initial molecule located in the skin. It undergoes a significant transformation under the influence of UV radiation.2. **Conversion to Cholecalciferol (Vitamin D3)**: - **UV Radiation (skin)**: Exposure to ultraviolet radiation from sunlight converts 7-dehydrocholesterol to cholecalciferol (Vitamin D3). - This conversion happens spontaneously after initial UV-induced transformation.3. **Hydroxylation in the Liver**: - **25-Hydroxylase (liver)**: This liver enzyme hydroxylates cholecalciferol (Vitamin D3) to form 25-hydroxycholecalciferol.4. **Further Hydroxylation in the Kidney**: - **1α-Hydroxylase (kidney)**: The kidney enzyme 1α-hydroxylase further hydroxylates 25-hydroxycholecalciferol to produce 1α,25-dihydroxycholecalciferol, also known as Active Vitamin D.5. **Roles of Active Vitamin D (1α,25-Dihydroxycholecalciferol)**: - **Intestine**: Active Vitamin D increases the absorption of calcium ions (Ca²⁺) from the diet in the intestine. - **Blood**: Active Vitamin D assists in maintaining calcium ion concentration in the blood. - **Bone**: Active Vitamin D also plays a role in the deposition and mobilization of calcium in bones as calcium phosphate hydroxyapatite (Ca₅(PO₄)₃OH).This pathway highlights the critical steps and enzymes involved in the activation of Vitamin D3, necessary for calcium metabolism and bone health in the human body.

As described in the diagram provides, active form of Vitamin D is needed for absorption of dietary…

Answered: After obtaining the results from the…

Biochemistry

9th Edition

ISBN:9781319114671

Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.

Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.

Chapter1: Biochemistry: An Evolving Science

Section: Chapter Questions

Problem 1P

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Introduction: A 2-year-old male named Justin. He is suffering from hypotonia (decreased muscle tone), weakness and growth failure, and is unable to walk. His mother has just brought him into the emergency room from the family beach house, where they have been spending the summer, because he has had a seizure. X-rays indicate that the toddler is suffering from rickets, which is a result of a nutritional deficiency of Vitamin D. But his mother insists that her son's diet is not Vitamin D-deficient. He drinks three glasses of milk a day, and his diet also includes meat and eggs.

A simplified scheme of Vitamin D metabolism is shown in the figure attached. The chemical name of active Vitamin D is 1a, 25-dihydroxycholecalciferol, and it is synthesized via the pathway shown. Catalysts, both in the form of enzymes and ultraviolet light, are required for Vitamin D synthesis. The two main sources of active Vitamin D are diet and sunlight.

Food supplemented with "Vitamin D" usually contains cholecalciferol (Vitamin D₃). In the liver, dietary cholecalciferol is converted to 25-dihydroxycholecalciferol. Next, in the kidney, that chemical is converted to active Vitamin D.

Sunlight is also responsible for producing Vitamin D. The skin contains a precursor, 7-dehydrocholesterol. In the presence of ultraviolet light, which acts as a catalyst, a ring-opening reaction occurs, which is followed by the spontaneous conversion of this intermediate to Vitamin D₃, and this follows the dietary Vitamin D₃ pathway to become active Vitamin D.

Active Vitamin D is a steroid-like compound that acts in combination with other hormones to increase the concentration of Ca²⁺ via a variety of mechanisms, one of which includes increasing the intestinal absorption of dietary calcium (intestinal absorption of dietary phosphate, a calcium counter-ion, also increases as a result). Calcium ions are required to form hydroxyapatite Ca₅(PO₄)₃OH, the main mineral constituent of bone.

It is decided to carry out further analysis and take a sample of Justin's blood. The laboratory results are attached:

A. After obtaining the results from the laboratory, it is suspected that the patient might have a defective enzyme in the Vitamin D synthetic pathway. Which enzyme is defective, and why?

This table provides laboratory test results for a patient, comparing their values with established normal ranges.

### Patient Laboratory Test Results

| Test | Patient | Normal Range |
|-----------------------------------------------------|---------|---------------|
| **Serum Calcium, mg/dL** | 5.1 | 8.7-10.1 |
| **Serum Phosphorous, mg/dL** | 4.2 | 2.4-4.3 |
| **Serum 1α, 25-dihydroxycholecalciferol, pg/mL** | 13 | 20-76 |
| **Serum 25-hydroxycholecalciferol, ng/mL** | 48 | 10-55 |

### Explanation of the Results

- **Serum Calcium (mg/dL)**:
- **Patient Value**: 5.1
- **Normal Range**: 8.7-10.1
- **Interpretation**: The patient's serum calcium level is significantly below the normal range, indicating possible hypocalcemia.

- **Serum Phosphorous (mg/dL)**:
- **Patient Value**: 4.2
- **Normal Range**: 2.4-4.3
- **Interpretation**: The patient's serum phosphorous level is within the normal range.

- **Serum 1α, 25-dihydroxycholecalciferol (pg/mL)**:
- **Patient Value**: 13
- **Normal Range**: 20-76
- **Interpretation**: The patient's level of 1α, 25-dihydroxycholecalciferol is below the normal range, which could suggest a deficiency in active vitamin D.

- **Serum 25-hydroxycholecalciferol (ng/mL)**:
- **Patient Value**: 48
- **Normal Range**: 10-55
- **Interpretation**: The patient's level of 25-hydroxycholecalciferol is within the normal range, indicating adequate storage level of vitamin D.

### Summary

The table highlights that the patient has notable deficiencies in serum calcium and 1α, 25-dihydroxycholecalciferol levels,

### Vitamin D3 Synthesis and Metabolism Pathway

This diagram outlines the synthesis and metabolism pathway of Vitamin D3, also known as cholecalciferol, highlighting the transformation at various stages under different conditions and enzymes. Here's a detailed explanation:

1. **7-Dehydrocholesterol**: This is the initial molecule located in the skin. It undergoes a significant transformation under the influence of UV radiation.

2. **Conversion to Cholecalciferol (Vitamin D3)**:
- **UV Radiation (skin)**: Exposure to ultraviolet radiation from sunlight converts 7-dehydrocholesterol to cholecalciferol (Vitamin D3).
- This conversion happens spontaneously after initial UV-induced transformation.

3. **Hydroxylation in the Liver**:
- **25-Hydroxylase (liver)**: This liver enzyme hydroxylates cholecalciferol (Vitamin D3) to form 25-hydroxycholecalciferol.

4. **Further Hydroxylation in the Kidney**:
- **1α-Hydroxylase (kidney)**: The kidney enzyme 1α-hydroxylase further hydroxylates 25-hydroxycholecalciferol to produce 1α,25-dihydroxycholecalciferol, also known as Active Vitamin D.

5. **Roles of Active Vitamin D (1α,25-Dihydroxycholecalciferol)**:
- **Intestine**: Active Vitamin D increases the absorption of calcium ions (Ca²⁺) from the diet in the intestine.
- **Blood**: Active Vitamin D assists in maintaining calcium ion concentration in the blood.
- **Bone**: Active Vitamin D also plays a role in the deposition and mobilization of calcium in bones as calcium phosphate hydroxyapatite (Ca₅(PO₄)₃OH).

This pathway highlights the critical steps and enzymes involved in the activation of Vitamin D3, necessary for calcium metabolism and bone health in the human body.

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