Biochemitsry - N2 Metabolism And Plasma Proteins

Question 1

Step 1 of Protein Translation

Answer 1

Initiation: during initiation, the components of the translational apparatus come together with an mRNA and a tRNA carrying the first amino acid (AA1) binds to the start codon (AUG)

Question 2

Step 2 of Protein Translation

Answer 2

Elongation: During elongation, AAs are brought to the mRNA by tRNAs and are added one by one to a growing polypeptide chain

Question 3

Step 3 of Protein Translation

Answer 3

Termination: during termination, a stop codon in the mRNA is recognized by a protein release factor, and the translational apparatus comes apart, releasing a completed polypeptide.

Question 4

Primary protein structure

Answer 4

A sequence of amino acids

Question 5

Secondary protein structure

Answer 5

H-binding of the peptide backbone causes the AAs to fold into a repeating pattern

Question 6

Tertiary protein sturcture

Answer 6

3D folding pattern of a protein due to side chain interactions

Question 7

Quaternary protein structure

Answer 7

Protein consisting of more than 1 AA chain

Question 8

General principles of protein modification, transport, and secretion (5)

Answer 8

1. Secretory pathway
2. Post-translational modification
3. Packaging
4. Vesicular transport: cellular destination, extracellular destination (signaling peptides)
5. Exocytosis: a form of secretion, best understood mechanism

Question 9

Steps of protein modification, transport, and secretion (5)

Answer 9

1A: RER synthesizes proteins and packages them in vesicles
1B: SER synthesizes lipids and has various other functions

2. Transport vesicles takes proteins and lipids to the Golgi apparatus
3. Golgi modifies the lipids and proteins from the ER; sorts and packages them back into secretory vesicles
4. Secretory vesicles travel to the plasma membrane, fuse, and expel their contents extracellularly
5. Simultaneously, material entering the cell via endocytosis fuse with a lysosome that contains digestive enzymes that break down contents for recycling

Question 10

Plasma proteins are composed of:

Answer 10

Protein and hetero-oligosaccharide chains that are short, branched, w/ or w/o negative charge, and have no repeating disaccharide units

Question 11

Plasma proteins contain:

Answer 11

N-terminal signal sequence that targets the growing polypeptide chain to the ER for N-glycosylation and then the Golgi for O-glycosylation.

Question 12

After modification in the Golgi, plasma proteins are:

Answer 12

Sorted and sent to their respective destinations: secreted from the cell (extracellular), incorporated into the cell membrane, targeted to lysosomes for recycling (defect causes I-cell disease!)

Question 13

Plasma proteins function in: (4)

Answer 13

1. Cell-surface recognition
2. Cell-surface antigenicity
3. Components of the ECM and mucins (for lubrication)
4. Globular proteins in plasma

Question 14

Plasma proteins are degraded by:

Answer 14

Lysosomal hydrolases, which can be affected by hereditary enzyme deficiencies that cause oligosaccharidoses

Question 15

Plasma proteins are derived from which sugar?

Answer 15

Mannose

Question 16

Describe the sugar conversion pathway in the making of plasma proteins (5)

Answer 16

1. Mannose is phosphorylated to mannose-6-phosphate
2. M6P then isomerizes to M1P
3. M1P then becomes GDP-mannose (GTP donation?)
4. GDP-mannose then becomes GDP-4-keto-6 deoxymannose
5. GDP-4-keto-6-deoxymannose is then converted to GDP-fucose, which eventually goes on to form plasma proteins (glycoproteins)

Question 17

What is dolichol phosphate?

Answer 17

Dolichol phosphate is the backbone of glycoprotein synthesis. Responsible for synthesis of the high mannose form of oligosaccharides in the RER.

Question 18

Plasma protein solubility and charge effects (3)

Answer 18

1. Plasma proteins are highly negatively charged: sugars contain many -OH groups
2. Hydrophilic
3. Water acts as a buffer and space filter (funnel) between transmembrane plasma proteins and molecules (like growth factors): The space helps with plasma protein recognition of molecules and consequential signaling

Question 19

Albumin characteristics and function (5)

Answer 19

1. Small, water soluble plasma protein with a long half-life
2. 60% of total plasma protein
3. Provides 70-80% of total osmotic pressure of plasma; helps maintain BP
4. Binds free FAs, Ca2+, zinc, steroid hormones, copper, and bilirubin
5. Many drugs can bind to albumin as well: decreases drug effectiveness and may lengthen lifetime in circulation

Question 20

Coagulation factors synthesized in the liver (classes [4] and agents)

Answer 20

1. Procoagulants: fibrinogen; prothrombin; factors V, VII, VIII, IX, X, XI, XII, XIII; thrombopoietin
2. Anticoagulants: protein C, protein S, tissue factor pathway inhibitor, anti-thrombin
3. Pro-fibrinolysis: Factor XIIa, plasminogen
4. Anti-fibrinolysis: plasminogen activator inhibitor-1, alpha-antiplasmin, tissue activatable fibrinolysis inhibitor

Question 21

Acute phase proteins are induced by:

Answer 21

Injury, toxins, or pathogens

Question 22

What is the acute phase response?

Answer 22

Injury, toxins, or pathogens increase the levels of IL-6 which induce hepatocytes to increase clotting factors, complement proteins, acute phase proteins, and decrease albumin. This pathway stimulates bone marrow to also increase leukocytosis.

Simultaneously, the brain is participating in thermoregulation and sickness behavior.

Question 23

What are some acute phase proteins? (7)

Answer 23

1. Complement proteins: C3, 4, 9
2. Iron-binding proteins: ferritin, haptaglobin
3. Antimicrobial proteins: antimicrobial peptide 2, hepcidin
4. Clotting factors
5. Inflammatory proteins: IL-6, LPS-binding protein, phospholipase A2
6. Lectins, pentraxins, ficolins, and collectins: CRP, mannose-binding lectin
7. Protease inhibitors: alpha2-macroglobulin, alpha1-antichymotryosin, and alpha1-antitrypsin

Question 25

What is I-cell disease?

Answer 25

Deficiency of phosphotransferase that stops mannose from being converted to M6P in the RER. As a result, synthesis of glycoproteins (plasma proteins) is halted. Patients presents with skeletal abnormalities, restricted joint movement, coarse facial features, and severe psychomotor impairment. Typically results in early childhood death.

Question 26

How does rheumatoid arthritis related to glycoproteins?

Answer 26

RA is an autoimmune reaction with a mannose-binding protein deficiency. This deficiency results in decreased glycoprotein (plasma protein) synthesis. Decreased glycoproteins then cause decreased production of mucin, which help with joint lubrication, leading to stiff, inflamed joints.

Question 27

What are genetic lysosomal hydrolase deficiency?

Answer 27

Deficiencies in lysosomal hydrolase cause intracellular glycoprotein accumulation, leading to toxicity. Manifests as mannosidoses, fucosidosis, aspartylglucosaminuria, sialidosis, Schindler disease. Can be treated with gene therapy, enzyme replacement therapy, and small molecules designed for reactivating defective enzymes.