Biochemistry of Glycosaminoglycans and PAPS

Questions and Answers

What is the primary role of 3’-Phosphoadenosyl-5’-Phosphosulfate (PAPS) in metabolic processes?

It serves as a sulfur donor in glycosphingolipid synthesis. (correct)

It acts as an energy source for cellular respiration.

It is a critical component of DNA synthesis.

It facilitates the hydrolysis of polysaccharides.

Which enzyme is responsible for sulfation of carbohydrate chains?

Sulfotransferase (correct)

Sulfide reductase

Glucuronic acid transferase

Uronosyl 5-Epimerase

A defect in the process of sulfation may lead to which of the following disorders?

Autosomal recessive disorders affecting skeletal development (correct)

Cardiovascular diseases

Diabetes mellitus

Arthritis

What type of reaction does Uronosyl 5-Epimerase catalyze?

Epimerization of D-sugar to L-sugar Signup and view all the answers

In which cellular organelle does core protein synthesis occur?

Endoplasmic reticulum (ER) Signup and view all the answers

What occurs to core proteins as they move through the ER?

They are glycosylated by membrane-bound transferases. Signup and view all the answers

What is the primary function of glucuronic acid in sulfation?

It provides sulfate through PAPS. Signup and view all the answers

What type of biochemical disorder can arise from a defect in glucuronic acid incorporation?

Skeletal system disorders Signup and view all the answers

Which of the following statements about 3’-Phosphoadenosyl-5’-Phosphosulfate (PAPS) is NOT true?

PAPS is synthesized without the involvement of glucuronic acid. Signup and view all the answers

Which of the following sugar nucleotides serves as a precursor for glycoproteins?

UDP-galactose Signup and view all the answers

What type of amino acid R-groups are specifically targeted for glycosylation by oligosaccharides?

Serine and Threonine Signup and view all the answers

Which of the following statements concerning UDP-N-acetylgalactosamine is true?

It donates sugars to growing carbohydrate chains. Signup and view all the answers

What is a common fate of N-linked glycoproteins within the cell?

They may be translocated to lysosomes. Signup and view all the answers

How are GDP-fucose and GDP-mannose related in terms of biosynthesis?

GDP-fucose is synthesized from GDP-mannose. Signup and view all the answers

What is the significance of the negative charge of CMP-NANA at physiological pH?

It aids in sugar donation to carbohydrate chains. Signup and view all the answers

Which of the following is NOT a sugar nucleotide involved in glycoprotein synthesis?

UDP-xylose Signup and view all the answers

In what cellular compartment does the glycosylation process occur for proteins synthesized on the ER?

Lumen of ER Signup and view all the answers

Which type of glycosylation involves the transfer of N-acetylgalactosamine from UDP-N-galactosamine?

O-Linked Glycosylation Signup and view all the answers

What structural role do carbohydrates play in glycoproteins?

They provide recognition signals for molecular interactions. Signup and view all the answers

What type of bond is formed between xylose and the hydroxyl group of serine?

O-glycosidic bond Signup and view all the answers

The alternating residues in bacterial cell walls consist mainly of which two components?

N-acetylmuramic acid and N-acetylglucosamine Signup and view all the answers

Which molecule cleaves the glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine?

Lysozyme Signup and view all the answers

What is the role of penicillin in relation to peptidoglycan?

Inhibit formation of cross-links Signup and view all the answers

What happens in glycoprotein storage diseases due to enzyme deficiency?

Accumulation of partially degraded structures Signup and view all the answers

Lysosomal hydrolytic enzymes are typically characterized as which of the following?

Exoenzymes specific for the removal of one component Signup and view all the answers

What is the significance of the low optimum pH (pH 5) in lysosomes?

It enhances the activity of lysosomal enzymes. Signup and view all the answers

Which process begins the synthesis of the carbohydrate chain in lysosomes?

Transfer of a xylose from UDP-xylose to a hydroxyl group. Signup and view all the answers

What is the half-life of hyaluronic acid within lysosomes?

3 days Signup and view all the answers

Which of the following statements about keratan sulfate is correct?

It has a half-life of 120 days. Signup and view all the answers

What occurs after a vesicle containing phagocytosed material fuses with a lysosome?

It forms a phagolysosome for degradation. Signup and view all the answers

Which enzyme is responsible for catalyzing the transfer of xylose in carbohydrate synthesis?

Xylosyltransferase Signup and view all the answers

What type of enzymes are found in lysosomes?

Hydrolytic enzymes known as acid hydrolases. Signup and view all the answers

How does sulfation occur during the synthesis of the carbohydrate chain?

After the monosaccharide has been incorporated into the chain. Signup and view all the answers

In what condition are lysosomal enzymes active?

In acidic environments around pH 5. Signup and view all the answers

What is the role of acid hydrolases in lysosomes?

To break down materials brought into the lysosome. Signup and view all the answers

What is required for the synthesis of N-Linked glycosides?

Dolichol and dolichol pyrophosphate Signup and view all the answers

Where does the synthesis of dolichol-linked oligosaccharides occur?

Lumen of the Endoplasmic Reticulum (ER) Signup and view all the answers

Which of the following sugars is NOT part of the oligosaccharide constructed on dolichol?

Galactose Signup and view all the answers

What characterizes the final processing of N-Linked oligosaccharides?

Removal of mannosyl and glycosyl residues followed by various sugar additions Signup and view all the answers

Which of the following is a characteristic of conditions caused by defects in N-Linked glycosylation?

Restricted joint movement Signup and view all the answers

What happens to the oligosaccharide during its transfer from dolichol to protein?

It is linked to an asparagine side group Signup and view all the answers

Which glycosaminoglycan (GAG) is not covalently attached to protein to form proteoglycans?

Hyaluronic acid Signup and view all the answers

Which feature is least likely to be associated with N-Linked glycosylation disorders?

Enhancement of motor skills Signup and view all the answers

What does the removal of specific residues during N-Linked oligosaccharide processing primarily lead to?

Modification of protein functions Signup and view all the answers

Which of the following substances is most directly linked through a pyrophosphate linkage to the oligosaccharide during its synthesis?

Dolichol Signup and view all the answers

Study Notes

3’-Phosphoadenosyl-5’-Phosphosulfate (PAPS)

PAPS is a molecule of AMP with a sulfate group attached to the 5’-phosphate.
Synthesis occurs after D-glucuronic acid is incorporated into the carbohydrate chain.
Acts as a source of sulfate and a sulfur donor in glycosphingolipid synthesis.

Sulfotransferase and Sulfation

Sulfotransferase facilitates sulfation of carbohydrate chains at specific sites.
Defects in sulfation can lead to autosomal recessive disorders affecting skeletal system development.

Core Protein Synthesis

Proteins synthesized in the endoplasmic reticulum (ER) are glycosylated by membrane-bound transferases.

Degradation of Glycosaminoglycans (GAGs)

GAG degradation occurs in lysosomes, containing hydrolytic enzymes active at pH 5, known as acid hydrolases.
Low pH protects the cell by preventing lysosomal enzymes from functioning in neutral cytosol.
GAGs have varying half-lives: hyaluronic acid (3 days), chondroitin and dermatan sulfate (10 days), keratan sulfate (120 days).

Synthesis of Carbohydrate Chain

Initiated by transferring xylose from UDP-xylose to serine/threonine hydroxyl group, catalyzed by xylosyltransferase.
Sequential addition of sugars occurs, involving alternating acidic and amino sugars and conversion of D-glucuronyl to L-iduronyl residues.

Addition of Sulfate Groups

Sulfation occurs after monosaccharides are incorporated into the growing carbohydrate chain.

Phagocytosis of GAGs

GAGs are phagocytosed into a vesicle that fuses with the lysosome, forming a phagolysosome for degradation.

Sugar Nucleotides

Serve as precursors for glycoprotein carbohydrate components, including UDP-glucose, UDP-galactose, UDP-N-acetylglucosamine, and others such as GDP-mannose.

Glycosylation of Proteins

Oligosaccharides are attached to specific amino acid R-groups based on protein's 3D structure.
Synthesis of O-linked glycosides occurs in the ER, transferring N-acetylgalactosamine onto seryl or threonyl R-groups.

Synthesis of N-Linked Glycosides

Occurs in the ER and Golgi apparatus, requiring dolichol and dolichol pyrophosphate.
Final processing involves removal of initial sugar residues and addition of various sugars.

Structure of Proteoglycans

All GAGs, except hyaluronic acid, attach covalently to proteins, forming proteoglycan monomers through O-glycosidic bonds to serine residues.

Bacterial Cell Wall Polysaccharides

Comprise alternating β (1→4)-linked N-acetylmuramic acid and N-acetylglucosamine residues, forming a mesh framework through cross-linking tetrapeptides.

Enzymatic Actions

Lysozyme cleaves glycosidic bonds in peptidoglycan, aiding in degradation.
Penicillin inhibits cross-link formation in peptidoglycan, serving as an antibiotic.

Lysosomal Glycoprotein Degradation

Lysosomal enzymes remove specific components of glycoproteins sequentially, primarily as exoenzymes.

Glycoprotein Storage Diseases

Result from deficiencies in degradative enzymes, causing accumulation of partially degraded structures in lysosomes.
Symptoms correlate with enzyme deficiencies seen in mucopolysaccharidoses and glycolipid degradation issues.

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Description

This quiz covers the biochemistry of 3’-Phosphoadenosyl-5’-Phosphosulfate (PAPS), its role in sulfation and glycosaminoglycan (GAG) degradation. Explore the mechanisms of sulfotransferase, synthesis of core proteins, and the effects of sulfation defects on skeletal development.