Musculoskeletal I Module: Biochemical Basis of Diseases

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Questions and Answers

What happens to elastin in the lung when neutrophils release elastase?

It is converted into a different protein

It is protected from damage

It is broken down (correct)

It becomes overproduced

What is the function of hyaluronic acid in the body?

To attract water and act as a lubricant (correct)

To break down elastin

To degrade glycosaminoglycans

To stimulate the production of purine nucleotides

What is the result of a deficiency of lysosomal enzymes?

Inhibition of glycosaminoglycan synthesis

Complete degradation of glycosaminoglycans

Overproduction of glycosaminoglycans

Partial degradation of glycosaminoglycans (correct)

What is the consequence of the accumulation of glycosaminoglycans in cells?

Enlargement of organs with impairment of their function Signup and view all the answers

What is the underlying cause of Lesch-Nyhan syndrome?

Deficiency of hypoxanthine-guanine phosphoribosyl transferase Signup and view all the answers

What is the effect of elastase on elastin?

It breaks down elastin Signup and view all the answers

What is the function of alpha 1-antitrypsin?

To inhibit the activity of elastase Signup and view all the answers

What is the role of repeating disaccharides of amino sugar and sugar acid in hyaluronic acid?

They attract water and act as a lubricant Signup and view all the answers

What is the result of adenosine deaminase deficiency?

Combined immunodeficiency syndrome Signup and view all the answers

What is the probable cause of adenosine deaminase deficiency?

Unknown cause Signup and view all the answers

What is the name of the genetic disorder caused by a deficiency of the enzyme in pyrimidine metabolism?

Orotic aciduria Signup and view all the answers

What is the name of the syndrome caused by HGPRT deficiency?

Lesch-Nyhan syndrome Signup and view all the answers

What is the primary cause of primary gout?

Variant form of PRPP synthetase Signup and view all the answers

What is the main characteristic of collagen?

Triple helix Signup and view all the answers

What is a common condition that leads to secondary gout?

All of the above Signup and view all the answers

What is the function of lysyl oxidase in collagen biosynthesis?

To form intramolecular aldol cross-links Signup and view all the answers

What is the main difference between glycoproteins and proteoglycans?

Glycoproteins have a higher carbohydrate content Signup and view all the answers

What is the effect of adenosine deaminase deficiency on the immune system?

Affects both cell-mediated and humoral immunity Signup and view all the answers

What is the main component of proteoglycans?

Carbohydrate Signup and view all the answers

What is the result of increased production of PRPP?

Increased production of uric acid Signup and view all the answers

What is the name of the enzyme involved in the first step of collagen biosynthesis?

Lysyl oxidase Signup and view all the answers

What is a consequence of enhanced turnover rate of nucleic acids?

Increased production of uric acid Signup and view all the answers

What is the main function of elastin?

To provide elasticity and recoil Signup and view all the answers

What is the main difference between collagen and elastin?

Collagen provides high tensile strength, while elastin provides elasticity and recoil Signup and view all the answers

What is the role of proteoglycans in the body?

They have a lubricant role and bind to large amounts of water Signup and view all the answers

What is the covalent bond formed between in proteoglycan aggregate formation?

Glucosaminoglycans and core proteins Signup and view all the answers

What is the classification of hyaluronic acid based on its sulfate content?

Sulfate-free GAG Signup and view all the answers

What is the enzyme responsible for hydroxylation of collagen?

Hydroxylase Signup and view all the answers

What is the rate-limiting step in de novo purine synthesis?

PRPP synthetase Signup and view all the answers

What is the parent precursor of purine nucleotides?

IMP Signup and view all the answers

What is the primary cause of scurvy?

Vitamin C deficiency Signup and view all the answers

What is the characteristic feature of Ehlers-Danlos syndrome?

Flexible joints and fragile skin Signup and view all the answers

What is the result of an amino acid substitution of glycine by a bulky amino acid in the collagen triple helix structure?

Bone deformities and fracture Signup and view all the answers

What is the primary defect in Marfan syndrome?

Genetic mutation in fibrillin gene Signup and view all the answers

What is the effect of vitamin C deficiency on collagen fibers?

Collagen fibers cannot be cross-linked, disturbing the tensile strength of collagen fibers Signup and view all the answers

What is the characteristic feature of osteogenesis imperfecta?

Bone deformities and fracture Signup and view all the answers

What is the result of a defective alpha-1 antitrypsin protein?

Liver disease Signup and view all the answers

What is the biochemical basis of Ehlers-Danlos syndrome?

Lysyl-hydroxylase enzyme deficiency Signup and view all the answers

Study Notes

Biochemical Basis of Musculoskeletal Conditions

Scurvy: caused by vitamin C deficiency, affecting hydroxylase, leading to collagen fibers unable to cross-link and disturbing tensile strength.
Ehlers-Danlos syndrome: caused by lysyl-hydroxylase enzyme deficiency, characterized by flexible joints and fragile skin.
Osteogenesis imperfecta: caused by amino acid substitution of glycine by a bulky amino acid in the collagen triple helix structure, leading to bone deformities and fractures.
Marfan syndrome: caused by genetic mutation in the fibrillin gene, leading to connective tissue disorders, impaired integrity in the skeleton, eye, and CVS, and abnormal growth of bone and soft tissue.

Elastin: alpha one antitrypsin deficiency, caused by mutation in the gene coding for alpha one antitrypsin, leading to defective alpha-1 antitrypsin protein, liver disease, and emphysema.
Marfan syndrome: caused by genetic mutation in the fibrillin gene, leading to connective tissue disorders, impaired integrity in the skeleton, eye, and CVS, and abnormal growth of bone and soft tissue.

Management of Osteoarthritis

Hyaluronic acid: binds to large amounts of water, has a lubricant role, and is used in the management of osteoarthritis.

Mucopolysaccharidoses

Deficiency of lysosomal enzymes, leading to partial degradation of GAGs, accumulation of large quantities of GAGs, and marked enlargement of organs with impaired function.
Lesch-Nyhan syndrome: caused by mutation in the salvage pathway of purine nucleotide, leading to deficiency of hypoxanthine-guanine phosphoribosyl transferase, accumulation of PRPP, and increased production of purine nucleotides, causing gout-like symptoms and neurological symptoms.

Adenosine Deaminase Deficiency

Severe combined immunodeficiency, affecting both cell-mediated and humoral immunity, caused by deficiency of adenosine deaminase, leading to buildup of dATP and inhibition of ribonucleotide reductase.

Gout

Primary gout: 1-inherited (90%), caused by variant form of PRPP synthetase, and 2-idiopathic.
Secondary gout: caused by overproduction of uric acid due to enhanced turnover rate of nucleic acids, defect in uric acid excretion, chronic renal failure, increased alcohol consumption, ketoacidosis, and thiazide diuretics.

Orotic Aciduria

Caused by rare genetic deficiency of the enzyme in pyrimidine metabolism (orotidine decarboxylase).

Comparisons in Musculoskeletal I

Collagen: has many different genetic types, triple helix structure, contains carbohydrate, and has high tensile strength with no stretch.
Elastin: has a single genetic type, no triple helix structure, does not contain carbohydrate, and has stretch and recoil properties.

Biochemical Aspects

ECM contains 3 major classes of biomolecules: fibrous (structural proteins), specialized proteins, and proteoglycans.
Proteoglycans: bind to large amounts of water, have a lubricant role, and are classified into sulfate-free and sulfate-containing GAGs.
Collagen biosynthesis: involves steps such as hydroxylation, glycosylation, and cross-linking formation.

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Description

This quiz covers the biochemical basis of various musculoskeletal diseases, including scurvy and Ehlers-Danlos syndrome.