1.06 Protein Degradation

Question 1

What is the difference between Protein & Polypeptide

Answer 1

Polypeptide: Long chain of amino acids
Peptide: Long chain of amino acids with structure (beta-sheets, alpha helices)

Question 2

What is primary and secondary active transport?

Answer 2

Primary moves molecules against concentration gradient by using ATP
Secondary transports gets the energy to move molecules against their gradient from other proteins

Question 3

When is protein used for energy provision?

Answer 3

Under starvation and stress

Question 4

As what form is nitrogen excreted?

Answer 4

Urea (83%)

Question 5

What are the fates and uses of amino acids?

Answer 5

Amino acids are obtained through digested protein and can then go on to become:
Body Protein
Purines, Pyrimidines, Porphyrins
Hormones
Neurotransmitter
Coenzymes
Acetyl-CoA:
 - Ketone Bodies
 - TCA Cycle --> Glucose 
                      --> CO2 + ATP

Question 6

Describe the concept of nitrogen balance

Answer 6

Positive nitrogen balance = intake exceeds excretion, such as in
o	Growing children
o	Pregnant women
o	Bodybuilders
Negative nitrogen balance – excretion exceeds intake, such as in
o	Protein deficient diet
o	Chronic infection
o	Cancer

Question 7

What are the various pool for nitrogen in the body?

Answer 7

Amino Acids
Dietary Proteins
Biosynthetic Products
Carbon Skeletons
Body Protein
NH3 --> Urea --> Excretion

Question 8

What is the fate of protein degradation?

Answer 8

Amino acids may be recycled or transformed
The carbon skeleton (after deamination) used used for biosynthesis & energy production while the amine moiety (NH3) is predominantly excreted

Question 9

How has the body overcome the large number of amino-acids requiring metabolism?

Answer 9

There are 20 amino acids in the body, this would required a large number of metabolic enzymes to direct flux
Cells have thus adopted a funnelling strategy

Question 10

What are and describe the cellular funnels

Answer 10

The Amino-transferases (transaminases)
Catalyse the transfer of an amino group from an amino acid to a keto–acid. This forms a different keto-acid and a different amino-acid.
Use a pyridoxyl-phosphate co-enzyme

Question 11

Describe the three major transamination reactions

Answer 11

Any amino acid (when transaminated) will make glutamate (amino-acid) from alphaketoglutarate (keto-acid). This is the most common reaction and funnels amino acids to glutamate
Oxaloacetate will form Aspartate
Pyruvate will form Alanine

Question 12

Describe the Glutamate/Glutamine Route of amino acid flux

Answer 12

Most peripheral tissues funnel towards glutamate
Glutamate may incorporate another NH3 group to form glutamine (requires energy)
Enzyme = glutamine synthase
Glutamine transports the two NH3 groups to the liver. It is a non toxic transport molecule and the body can withstand high concentrations.

Question 13

Describe the Alanine route of amino acid flux

Answer 13

Route primarily used by muscles
Pyruvate is formed from glycolysis
The transamination of pyruvate forms alanine
Alanine is transported to the liver
Alanine may then be used in gluconeogenesis

Question 14

Describe how nitrogen is released

Answer 14

Nitrogen is released via oxidative deamination, in the form of ammonia
The primary substrate is glutamate
Major enzyme is glutamate dehydrogenase
Product is alpha-ketoglutarate
Reaction occurs predominantly in the liver & kidney

Question 15

Briefly describe the fates of ammonia and ammonium

Answer 15

Ammonia & Ammonium are highly toxic to humans
Ammonium is excreted by the kidney
Ammonium is converted to urea for excretion

Question 16

Briefly describe the urea cycle

Answer 16

Urea contains two nitrogen atoms synthesised using CO2
The synthesis of urea requires a multi-step pathway. The urea cycle (or ornithine cycle) mediates this
The cycle occurs almost exclusively in hepatocytes
Urea cycle is “split” between the cytosol and mitochondrial matrix
Urea is excreted from the body via the kidney

Question 17

Describe the first step of the urea cycle

Answer 17

Commitment of nitrogen to the urea cycle
NH3 from oxidative deamination (mainly)
Occurs in the mitochondrial matrix
Enzyme is carbamoyl-phosphate synthase
Co2 + NH3 → carbomoyl-phosphate. Reaction has a high energy demand

Question 18

Describe how the first step of the urea cycle is regulated

Answer 18

Regulation is allosteric
Modulator – N-acetylglutamate (NAG)
NAG is formed by glutamate and acetyl-CoA
High [glutamate] indicates increased amino acid flux.
- High protein –> high amino acids –> high amino acids –> increased production of glutamate from alphaKG (transamination) –> high glutamate

Question 19

What is the first entry point for nitrogen into the urea cycle?

Answer 19

Substrate is carbamoyl-phosphate
Carbamoyl-phosphate formed from NH3
NH3 formed from oxidative deamination
Reaction requires 2 molecules of ATP
Mitochondrial location

Question 20

What is the second entry point for nitrogen into the urea cycle?

Answer 20

Substrate is aspartate
Cytosolic entry point
N-group carried in aspartate following transamination (from OAA)
C-skeleton of aspartate “expelled” (or recycled) as fumerate

Question 21

List the steps in the urea cycle

Answer 21

Carbamoyl-Phosphate + Ornithine –> Citrulline
Citrulline + Aspartate –> Argino-Succinate
Agino-Succinate –> Arginine + Fumerate
Arginine –> Urea + Ornithine (cycle can start again)

Question 22

How are the TCA cycle and Urea cycle linked?

Answer 22

Argino-succinate

Question 23

What are the fates of the carbon skeletons after the removal of nitrogen as urea?

Answer 23

Can go on to form glucose (via OAA –> pyruvate –> glucose) or Ketone bodies (OAA –> Pyruvate –> AcetylCoA –> Acetoacetate –> Ketone Bodies)