Garrod hypothesized that “inborn errors of metabolism” such as alkaptonuria occur because _____.

Here we will talk about Why Garrod hypothesized that “inborn errors of metabolism” such as alkaptonuria occur because _____. Below is the answer and explanation to the biology question.

Garrod hypothesized that “inborn errors of metabolism” such as alkaptonuria occur because _____.

1. Genes dictate the production of specific enzymes, and affected individuals have genetic defects that cause them to lack certain enzymes
2. Metabolic enzymes require vitamin cofactors, and affected individuals have significant nutritional deficiencies
3. Certain metabolic reactions are carried out by ribozymes, and affected individuals lack key splicing factors
4. Enzymes are made of DNA, and affected individuals lack DNA polymerase

Inborn errors of metabolism

Inborn errors of metabolism, also known as hereditary enzyme disorders, are diseases caused by defects in enzymes in the metabolic process.

Inborn errors of metabolism are structural abnormalities in enzymes due to mutations in the structural genes that encode enzyme proteins. It is an inborn metabolic disorder caused by an abnormality in the amount of enzyme protein due to an abnormality in the regulatory system of the gene.

The mode of inheritance is generally autosomal recessive. Inborn metabolic defects can occur in any organism other than viruses and phages.

The various nutritional deficiency phenotypes are the result of inborn metabolic defects in the metabolism of amino acids, nucleotides, or vitamins. Nutritional deficiency phenotypes are an important tool in genetic studies, especially in microbial genetics.

A. E. Garrod, an English medical scientist, conducted a detailed study of patients with urine aciduria, cystinuria, albinism, and pentosuria from 1902 to 1908. It was pointed out that these diseases were caused by an inherited disorder of an enzymatic reaction in one of the metabolic pathways.

This led to the concept of inborn metabolic defects. Garrod’s hypothesis was confirmed only half a century later.

Mechanisms

Enzyme proteins are all encoded by genes. If a mutation in a gene encoding an enzyme protein alters the active center of the encoded protein, the activity of the enzyme is often reduced or even lost. Then the activity of the enzyme is often reduced or even completely lost, and the corresponding biochemical reaction cannot proceed smoothly.

This can result in the accumulation of substrates or precursors for the reaction or in a shortage of normal or abnormal products.

If the precursors are toxic or the normal products are necessary, it can bring about inborn abnormal metabolic diseases.
Phenylalanine is catalyzed by phenylalanine hydroxylase to become tyrosine.

If a mutation in the gene encoding this enzyme prevents this reaction from proceeding smoothly. Then phenylalanine accumulates in the body and abnormal products such as phenylpyruvate, phenyl lactate, phenylacetic acid, and o-hydroxyphenylpyruvate, which are oxidation products of phenylalanine, appear in the urine. This leads to phenylketonuria; patients have impaired brain development and most are mentally retarded.

Since the normal product tyrosine is in turn a precursor of melanin, the deficiency of tyrosine causes patients to have lighter hair and skin color.

Tyrosine undergoes many biochemical reactions to produce melanin on the one hand. On the other hand, it undergoes two biochemical reactions to become uronic acid. The latter is further broken down into fulvic acid and acetoacetic acid or transformed into a tawny substance.

How to prevent Inborn errors of metabolism?

The main measures to genetically reduce the incidence of inborn errors of metabolism in the population are.

1) Avoiding consanguineous marriages

2) Genetic counseling

Based on the distribution of patients in the family and the mode of inheritance of the disease, the probability of having a child with the disease can be estimated. It is possible to decide whether to have children or to continue the pregnancy, etc.

(3) Heterozygous detection of recessive heterozygotes has a normal appearance, but the activity of the corresponding enzyme is often between normal and recessive pure heterozygotes.

Therefore, heterozygotes can be detected by measurement of enzyme activity, but if the results of the measurement overlap with normal values, other methods must be used. For example, the phenylalanine tolerance test can be used to detect heterozygotes for phenylketonuria.

Detection of heterozygotes in groups in areas of high prevalence can be effective in preventing the occurrence of inborn metabolic deficiency disorders.

4) Prenatal diagnosis

Certain inborn metabolic defects can be detected by measuring the enzyme activity of fetal desmoplastic cells in cultured amniotic fluid. As of 1979, 75 congenital metabolic defects could be detected by this method.

Some metabolic defects such as Duchenne muscular dystrophy or pseudohypertrophic dystrophy can be detected by fetal endoscopic aspiration of fetal blood specimens.

Since the 1980s, recombinant DNA technology has been used to prenatally diagnose congenital metabolic defects, thus moving to the level of genetic diagnosis. This is of great help in guiding abortions, especially for pregnant women who have already given birth to a child with congenital metabolic defects.

How to treat inborn metabolic defects?

The main treatment for inborn metabolic defects is enzyme therapy.

Since the 1970s, microcapsules (artificial cells) made of enzymes packed in nylon film that degrade in the body, and the regular administration of these artificial cells to patients are promising methods of treating enzyme defects.

Supplementation of deficient metabolites, avoidance of exposure to triggering substances, induction of metabolism to reduce the accumulation of substances in the body. The use of inhibitors, coenzymes, limiting the intake of substrates of the defective enzyme, and supplementation of the deficient substance are all common clinical therapies.

Correct Answer

Here is the correct answer to Garrod hypothesized that “inborn errors of metabolism” such as alkaptonuria occur because _____.

Garrod hypothesized that “inborn errors of metabolism” such as alkaptonuria occur because genes dictate the production of specific enzymes, and affected individuals have genetic defects that cause them to lack certain enzymes.

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