Question

In addition to tryptophan, which of the following amino acids is likely to be deficient in Hartnup disease? A. Aspartate B. Leucine C. Lysine D. Proline E. All of the above

Short answer

Answer: B. Leucine, D. Proline

Step-by-step solution

Hartnup Disease Overview

Hartnup disease is a rare genetic disorder that affects the absorption of neutral amino acids, including tryptophan. This absorption issue occurs across the small intestine and renal tubules. Due to the deficiency of these amino acids, the body cannot produce proteins and other essential molecules properly.

Identifying Affected Amino Acids

Since Hartnup disease affects the absorption of neutral amino acids, we must identify which of the given options are neutral amino acids: A. Aspartate - Acidic B. Leucine - Neutral C. Lysine - Basic D. Proline - Neutral E. All of the above

Solution

Out of the given options, only Leucine (B) and Proline (D) are neutral amino acids. Since it is not stated that all neutral amino acids are affected by Hartnup disease, we cannot conclude that (E) All of the above is the correct answer. However, since both Leucine and Proline are neutral amino acids, they are likely to be deficient in Hartnup disease. Therefore, the answer includes both B. Leucine and D. Proline.

Key concepts

Neutral Amino Acids Deficiency

Understanding Hartnup disease requires a basic knowledge of amino acids, specifically the role of 'neutral amino acids' in health. Neutral amino acids, like leucine, isoleucine, valine, proline, tryptophan, and others, are vital for various bodily functions, including the synthesis of proteins. Deficiency in these can lead to signs and symptoms such as those seen in Hartnup disease, where the body struggles with the absorption and subsequent utilization of these molecules.

In individuals with Hartnup disease, the body's inability to absorb neutral amino acids properly can result in a cascade of inadequacies. This abnormality is due to defects in the transporters responsible for their absorption in the intestine and reabsorption in the kidneys. Without enough neutral amino acids, patients may experience conditions like pellagra, which is associated with tryptophan deficiency and subsequent niacin (Vitamin B3) shortage. Since niacin is essential for energy production and DNA repair, its lack manifests as dermatitis, diarrhea, and dementia—the classical triad of pellagra symptoms.

Therefore, while tryptophan is often spotlighted in Hartnup disease, other neutral amino acids like leucine and proline are equally important. These amino acids contribute to a wide range of bodily functions, from supporting immune response to regulating blood sugar levels. A deficiency in these can significantly impair overall health and wellbeing, emphasizing the need to understand and manage Hartnup disease effectively.

Hartnup Disease Genetics

Hartnup disease is a genetic disorder inherited in an autosomal recessive pattern, implying that a person must inherit two copies of the defective gene, one from each parent, to develop the disease. The genetics of Hartnup disease involve mutations in the SLC6A19 gene which codes for a protein that functions as a transporter for neutral amino acids in the intestines and kidneys.

The gene mutations result in a dysfunctional transporter, leading to poor absorption and increased excretion of these amino acids. Genetic testing can identify carriers who have one copy of the mutation and may pass it to their offspring. To grasp the full picture, individuals diagnosed with Hartnup disease or those with a family history of the condition should consider genetic counseling. This aids in better understanding the risks, implications for future offspring, and the genetic nature of the disorder.

Knowledge of the genetics behind Hartnup disease also paves the way for potential future treatments, such as gene therapy, that target the root cause rather than just managing symptoms. As research progresses, understanding the genetics behind this disorder generates hope for more effective strategies to combat the challenges it presents.

Protein Synthesis Disruptions

Protein synthesis is a fundamental biological process where cells build proteins, which are crucial for structure, function, and regulation of the body's tissues and organs. Disruptions in this process can have severe consequences, as seen in conditions like Hartnup disease. When neutral amino acids are deficient due to poor absorption, the spectrum of amino acids available for protein construction is limited, leading to incomplete or faulty proteins.

The impact of protein synthesis disruption varies depending on the role of the missing amino acids. Structural proteins may lose their integrity, enzymes could become less efficient or inactive, and transport proteins may fail to transport substances correctly. All these disruptions can contribute to the variety of symptoms experienced by those with Hartnup disease, from skin issues to neurological problems.

Moreover, it's not just the deficiency of neutral amino acids that can disturb protein synthesis. Secondary deficiencies, such as niacin deficiency secondary to tryptophan malabsorption, further impact protein synthesis by affecting coenzymes that are critical for metabolic reactions. Understanding and managing these disruptions is a key aspect of mitigating the effects of Hartnup disease and improving patient outcomes.