Inborn Errors of Metabolism Overview

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Questions and Answers

What did Beadle and Tatum propose about metabolic processes?

Each step is controlled by multiple genes

Each step is controlled by a specific gene (correct)

Each step is controlled by environmental factors

Each step is independent of genes

Inborn errors of metabolism (IEMs) can be grouped by all of the following EXCEPT:

Metabolic pathway

Geographical location of the population (correct)

Cellular organelle involved

Main class of metabolite

What was the overall incidence of IEMs in the population according to the study in British Columbia?

Approximately 20 per 100,000 live births

Approximately 80 per 100,000 live births

Approximately 60 per 100,000 live births

Approximately 40 per 100,000 live births (correct)

What concept did Garrod introduce at the beginning of the twentieth century?

'One gene–one enzyme' concept Signup and view all the answers

How did Beadle and Tatum characterize metabolic processes?

As consisting of steps controlled by a particular enzyme and gene Signup and view all the answers

What percentage of all single gene disorders did IEMs make up in the population according to the study in British Columbia?

Approximately 15% Signup and view all the answers

Which type of inheritance is most commonly followed by Inborn Errors of Metabolism (IEMs)?

Autosomal recessive Signup and view all the answers

In autosomal IEMs, the defective protein is typically a diffusible ___.

Enzyme Signup and view all the answers

Which type of inheritance can manifest in the heterozygous state due to haploinsufficiency or dominant-negative effects?

Autosomal dominant Signup and view all the answers

What is the enzyme deficiency responsible for phenylketonuria?

Phenylalanine hydroxylase (PAH) Signup and view all the answers

What is the consequence of the enzyme block in phenylketonuria?

Accumulation of phenylalanine Signup and view all the answers

How did Bickel suggest treating phenylketonuria (PKU)?

Removal of phenylalanine from the diet Signup and view all the answers

What is the consequence of a deficiency of tyrosine in children with PKU?

Development of blond hair and blue eyes Signup and view all the answers

Which individual identified PKU as the first genetic disorder in humans caused by a specific enzyme deficiency?

Jervis Signup and view all the answers

In which part of the brain may children with PKU lack pigment due to the enzyme block?

Substantia nigra Signup and view all the answers

What is the typical eye color seen in children with PKU?

Blue eyes Signup and view all the answers

Which of the following disorders is NOT mentioned as an example in the chapter?

Sickle cell anemia Signup and view all the answers

What is the number of genes associated with a clinical phenotype due to mutations mentioned in the chapter?

Almost 3000 Signup and view all the answers

In which category of proteins do mutations often disrupt cell and organ function differently from the hemoglobinopathies?

Structural proteins Signup and view all the answers

What type of disorder did the text mention as included because it best demonstrates a specific principle?

Less common disorders Signup and view all the answers

What did the text outline in Chapter 11 provide a framework for understanding?

Pathogenesis of genetic disease Signup and view all the answers

What is one of the well-known disorders examined in the chapter?

Familial hypercholesterolemia Signup and view all the answers

Which type of proteins are present in virtually every cell and have fundamental roles in maintaining cell structure and function?

Housekeeping proteins Signup and view all the answers

What is the consequence of the absence of phenylalanine hydroxylase (PAH) activity in the liver due to phenylketonuria?

Brain damage Signup and view all the answers

Which proteins are produced in only one or a limited number of cell types and have unique functions contributing to the individuality of the cells?

Specialty proteins Signup and view all the answers

What is the relationship between mutation in a tissue-specific protein and disease?

May produce secondary effects on other tissues Signup and view all the answers

What can be inferred about the site of a protein’s expression and the site of disease?

There may be secondary effects on other tissues Signup and view all the answers

What is the consequence of mutation in a tissue-specific protein?

Leaves the tissue expressing the mutant protein unaffected by the pathological process Signup and view all the answers

What generalizations can be made about the clinical effects of mutations in housekeeping proteins?

Mutations in housekeeping proteins often have clinical effects in most or all tissues Signup and view all the answers

How many protein-coding genes are typically expressed by most cell types in humans?

$10,000 to 15,000$ Signup and view all the answers

Study Notes

Beadle and Tatum's Proposals

Proposed that each gene is responsible for the production of a single enzyme, characterizing metabolic processes as interactions between specific genes and their corresponding enzymes.

Inborn Errors of Metabolism (IEMs)

IEMs can be grouped by various characteristics, though they do not categorize by dietary habits or lifestyle choices.
Incidence in British Columbia reported approximately 1 in 1,000 births for IEMs.
IEMs constitute roughly 10% of all single gene disorders in the population.
Typically, IEMs follow an autosomal recessive inheritance pattern.

Historical Concepts

Garrod introduced the concept of "inborn errors of metabolism" at the beginning of the twentieth century, linking genetic mutations to metabolic disorders.

Phenylketonuria (PKU) Insights

Phenylketonuria is caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH).
The enzyme block in PKU leads to the accumulation of phenylalanine, which is toxic to the brain.
Suggested treatment for PKU includes a low-phenylalanine diet, emphasizing the importance of dietary management.
Children with PKU suffer from a deficiency of tyrosine due to the inability to metabolize phenylalanine properly.
PKU was identified as the first genetic disorder linked to a specific enzyme deficiency by Archibald Garrod.

Clinical Presentations and Effects

The absence of PAH activity results in intellectual disability and other neurological issues due to elevated phenylalanine levels.
Children may have a lack of pigment in the basal ganglia of the brain caused by the enzyme block; commonly exhibit lighter eye colors such as blue or green.

Protein Function and Genetic Disorders

The chapter discusses around 2,400 genes associated with clinical phenotypes due to mutations.
Distinct categories of proteins include housekeeping (present in all cells) and tissue-specific proteins (unique roles in certain cells).
Mutations in housekeeping proteins generally affect all cell types, while mutations in tissue-specific proteins lead to localized effects in specific tissues.
Disease manifestation is linked to the expression site of a protein, emphasizing that mutations can indicate specific organ or tissue dysfunctions.

Protein Expression and Human Genetics

Most human cell types express about 20,000 protein-coding genes, highlighting the complexity of gene regulation and expression across different tissues.

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Description

Test your knowledge of inborn errors of metabolism (IEMs) and mitochondrial disorders with this overview of single-gene biochemical or metabolic diseases. Explore the fascinating area of medicine and gain insight into the concept of 'chemical individuality' introduced by Garrod.