WK 6 & 7 (Protein metabolism)

Question 1

Endopeptidase

Answer 1

catalyse hydrolysis of peptide bonds AWAY from the end of the chain

Question 2

Exopeptidase

Answer 2

catalyse hydrolysis of peptide bonds at the end of the chain

Question 3

Stage 1 - The catabolism of proteins

Answer 3

The initial stages of catabolism of proteins begins with the denaturation (unfolding from final tertiary conformation) which is facilitated by breaking the non-covalent bonds involved in the acid environment of the stomach. Following denaturation, peptidase catalysed proteolysis begins. The endopeptidase pepsin catalyses the hydrolysis of ~10% of peptide bonds in a protein to liberate small peptides.
These peptides are subsequently hydrolysed into free amino acids by a series of endopeptidases (eg. trypsin, chymotrypsin) and exopeptidases in the small intestine and absorbed into the blood steam.

Question 4

Stage 2 Catabolism of proteins/ Amino acids

Answer 4

Stage 2 of catabolism of the now free AA begins with the active transport of AA into cell cytoplasm by carrier protein mediated and often Na+ dependent active amino transport systems.

Catabolism or AA degradation can be viewed as 2 components:
amino group removal or deamination
carbon skeleton degradation to metabolic intermediates.

Question 5

Oxidative deamination

Answer 5

For most AA is catalysed by transaminases (or aminotransferases) which transfer the amino group from the amino acid to alpha ketoglutarate to form an alpha keto acid and glutamate. The glutamate molecule is subsequently deaminated to liberate an ammonium ion (NH4+) and NADH. This ammonium ion is then excreted in the form of urea derived from the urea cycle (terrestrial vertebrates) or uric acid (birds, reptiles, insects)
Exceptions to this scheme are the amino acids serine and threonine which can be directly deaminated due to the presence of a hydroxyl group on the beta- carbon atom of both amino acids.

Question 6

Carbon skeleton degradation

Answer 6

The carbon skeletons (post deamination) give rise to 7 common metabolic intermediates.
The AAs that oxidise to acetyl-CoA or acetoacetyl-CoA are called ketogenic. The AAs that oxidise to pyruvate or one of the citric acid cycle intermediates (-Ketoglutarate, Succinyl-CoA, Fumerate or Oxaloacetate) are called glucogenic.
Only leucine and lysine are purely ketogenic. Isoleucine, phenylalanine, tryptophan and tyrosine are both ketogenic and glucogenic (ie. formation of both Acetyl-CoA and carboxylic acid cycle intermediates or alternate pathways). The14 other AA are purely glucogenic.

Question 7

Ketogenic

Answer 7

Results in the formation of ketone bodies. (Eg. Beta-hydroxybutyric acid, acetoacetic acid). Potentially give rise to ketosis: production of excess ketone bodies in blood (Ketoacidosis).

Question 8

Glucogenic

Answer 8

Net synthesis of glucose from these amino acids is feasible via citric acid cycle intermediates and pyruvate (gluconeogenesis). The degradation of these AA does not result in the formation of ketone bodies.

Question 9

Do proteins exposed to high concentrations of urea denature?

Answer 9

Yes

Question 10

What is the major site of oxidative deamination in mammals?

Answer 10

Liver

Question 11

Oxidative deamination of amino acids is a process:

a) During which amino acids are oxidised to carbon dioxide and water
b) Where amino nitrogen from amino acids is removed and liberated as ammonia
c) catalysed by peptidases
d) in which amino acids are utilised to synthesise proteins

Answer 11

b)

Question 12

Non-essential amino acids

Answer 12

amino acids that can be synthesised from common metabolic intermediates

Question 13

Essential amino acids

Answer 13

Amino acids that must be supplied in the diet, as insufficient synthesis occurs to fulfil

Question 14

Examples of essential amino acids

Answer 14

Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan and Valine

Question 15

Pathways for amino acid biosynthesis are diverse but what are the common features

Answer 15

1. Amino groups are furnished by transamination of amino groups from glutamine or glutamate
2. Carbon skeleton come from intermediates of: Glycolysis, Citric acid cycle or Pentose phosphate pathway
3. All pathways can be observed as belonging to 1 of 6 generalised biosynthetic families

Question 16

When are amino acid disorders most commonly encountered?

Answer 16

In the neonatal period and are usually fatal if not treated

Question 17

Maple syrup urine disease

Answer 17

Keto acid decarboxylase complex in mitochondria is defective.
Clinical signs include:
listlessness, vomiting, distinctive odour.
Results in: acidosis, coma, death in newborn cows.

Question 18

Are the consequences of disorders of protein/amino acid metabolism reversible?

Answer 18

No

Question 19

Amino acid biosynthesis is:
a) a mechanism that occurs only in the liver

b) A process that utilises only pyruvate as a substrate
c) coordinated by multiple feedback mechanisms on regulatory enzymes of the biosynthetic pathways
d) Unregulated and occurs constantly as proteins are important

Answer 19

c)