Hepatic Protein metabolism and amino acids in nitrogen balance

Question 1

Nitrogen balance

Answer 1

• Positive nitrogen -> gain of protein -> anabolic
• Negative nitrogen ->protein lost -> catabolic
• No amino acid is stored
• The main source of nitrogen is from dietary protein, the main loss from the gut and kidneys (as urea).
• Nitrogen balance is said to be in equilibrium when the intake and the output of nitrogen is roughly equal.

Question 2

Kwashiorkor: adequate calories/ inadequate protein

Answer 2

• Protein-energy malnutrition
• Marasmus: both protein and calories insufficient
• Features: oedema, fatty liver, dermatoses
• The body maintains a pool of free amino acids in the blood. In a fed state, the net contributor is the diet; in a fasting state it is bodily protein (of which 80% is in skeletal muscle).
• Amino acids may be used in liver for protein formation or used to make other nitrogen containing products
• Some enter systemic circulation to form building blocks for proteins in a different way
• Those that cannot be used in this way can have amino group removed and carbon backbone is used to form metabolic substrates

Question 3

Transport of free amino acid

Answer 3

Co-transported across enterocyte membrane with a sodium ion

Then it is actively transported over basolateral membrane into the portal circulation which then travels to the liver

Question 4

important hepatic proteins

Answer 4

• ALBUMIN
• Coagulation Factors
• IGF-1
• C-Reactive Protein
• Carrier proteins (eg caeruloplasmin)
• Apolipoproteins (for lipoproteins)

Question 5

Transamination of Alanine

Answer 5

• In most transamination reactions, a-ketoglutarate and glutamate form one of the a-ketoacid/amino acid pairs.
• This means a-ketoglutarate is a receiver of nitrogen (the amino group), which is transferred to glutamate.
amino acids cannot be stored therefore the carbon backbone can be preserved in a nitrogenous group excreted as waste

Question 6

Protein Degradation

Answer 6

1. Faulty/aging/obsolete proteins
2. Signal transduction
3. Flexible system to meet protein/energy requirements of environment
   Main means: 1. PROTEASOME (ubiquitin-dependent)
   2. LYSOSOME

Question 7

Ubiquitin: the mark of death

Answer 7

• Small protein
• Carboxyl group forms isopeptide bond with multiple Lysine residues
• Three enzymes involved:
E1 Ubiquitin-activating enzyme
E2 Ubiquitin-conjugating enzyme
E3 Ubiquitin-protein ligase
• Formation of ubiquitin chains (stronger signal, esp if >4)

Question 8

proteasome

Answer 8

contains ATP dependent hydrolases which break down an Ubiquitin tagged protein

Question 9

cap

Answer 9

regulatory sub-unit, regulated which enzymes enter the proteasome unit for destruction

Question 10

Lysosomal

Answer 10

Proteolytic enzymes within lysosome separated from cytosolic components

Question 11

MACROAUTOPHAGY - non-selective

Answer 11

ER derived autophagisomes engulf cytosolic proteins/aggregates organelles. Lysosome fuses with this to initiate proteolysis.

Question 12

MICROAUTOPHAGY-non-selective

Answer 12

Invaginations of lysosomal membrane engulf proteins/organelles.

Question 13

CHAPERONE-MEDIATED AUTOPHAGY-selective

Answer 13

Chaperone protein hsc70, in cytosol and intralysosomal, accompany specific cytosolic proteins in response to stressors (fasting/ oxidative stress etc).

Question 14

Cystinosis

Answer 14

• Genetic condition
• Autosomal recessive
• 1 in 200,000
• Defect in transporter leads to cystine accumulation in tissue lysosomes
• Eye and kidney problems