Liver Metabolism 5: N2 Metabolism And Synthesis Of Plasma Proteins

Question 1

What is the most produced plasma protein produced in the liver?

Answer 1

Albumin (12g/day) and roughly 55% of all plasma protein production
- IgG is second at roughly 15-20%

liver produces 20g of total proteins daily

Question 2

What are glycoproteins?

Answer 2

Proteins that contain oligosacchardies and heterooligo-saccharide chains
- chains care short branched with no repeating disaccharide units

Also contain N-terminal signal sequences that target the polypeptide chain and transport it to the lumen of the ER for N-glycosylation AND/OR the golgi for O-glycosylation

Then these proteins are packed and sent out of cell or incorporated in cell membrane.

• *functions include:
• cell surface recognition
• cell surface antigenicty
• globular proteins in plasma
• Extracellular matrix functions
• mucins in the stomach

Question 3

What is the pathogenesis of I-cell disease briefly?

Answer 3

Lysosomes are defective and target growing glycoproteins prematurely

Question 4

Dolichol phosphate

Answer 4

A molecule that plays a key role in synthesis of High mannose form of oligosaccharides

Is found throughout the rough endoplasmic reticulum

Question 5

Glycoprotein charge effects

Answer 5

Are highly negatively charged and hydrophillic
- due to excess OH- groups present

Water acts as buffer and space filler
- also orients water through cohesion

Question 6

Albumin

Answer 6

585 aa
- water soluble protein

Makes up 60% of total plasma protein concentration

Main functions is to:

• provides 70-80% of total osmotic pressure of plasma
• bind to free FAs/calcium/zinc/steroid hormones/copper/bilirubin

Question 7

Liver acute phase response protein synthesis

Answer 7

occurs by liver injury, presence of toxins or pathogens

Liver:

• decreases albumin
• increases clotting factors (fibrinogen/factor 8/9/vWF)
• increases complement proteins (C3/4/9)
• increases acute phase proteins (haptoglobin/ferritin/hepcidin)
• increases inflammatory proteins

Brain:

• increases thermoregulation
• induces “sickness behavior”

Question 8

I cell disease

Answer 8

Deficiency of enzyme that phosphorylates mannose at the Carbon-6 site (“phosphotransferase”)
- results in mannose being degraded lysosomes quickly and overall decrease in protein production in liver

Symptoms:

• skeletal abnormalities
• joint restriction
• coarse facial features
• severe psychomotor impairment
• death in early childhood
• hepatosplenomegaly

Question 9

difference between proteasome and lysosomal degradation

Answer 9

Proteasome:

• selectively degrade damaged or short-lived proteins
• uses ubiquitination to modify target proteins
• REQUIRES ATP

Lysosomal:

• no selective degradation and engages in Autophagy and heterophagy
• mTOR pathway = Autophagy
• uses acid hydrolyses to break down peptide bonds

Question 10

Positive vs negative nitrogen balance

Answer 10

Positive = intake exceeds excretion
- observed in childhood, pregnancy, recovering from emancipating illnesses

Negative = excretion exceeds intake
- observed in trauma, burns, illness, surgery

Question 11

How many amino acids are generates per day?

Answer 11

30-40g/day