Biochem revision - Week 7 Protein Metabolism in Exercise

Question 1

What is a protease? What is the protease in the stomach?

Answer 1

A protease is an enzyme that catalyzes the proteolysis, breaking down proteins into smaller polypeptides or single amino acids

Pepsin is the protease in the stomach. Once pepsinogen encounters HCL (mixing with gastric juices), it unfolds and catalyzes the cleavage of part
of its own polypeptide chain, thus producing pepsin.

Pepsin then hydrolyses other pepsinogen molecules to accelerate its own production.

Question 2

What does HCl do in the stomach?

Answer 2

HCl denatures proteins, unfolding their 3-D structure to reveal a polypeptide chain

Pepsin can then take over enzymatic digestion, forming shorter polypeptides

Question 3

How are the four enzymes that catalyze proteolysis in the small intestine activated?

Answer 3

Endopeptidase hydrolyses a specific bond in trypsinogen as it enters the duodenum, thus producing trypsin

Trypsin then hydrolyses other trypsinogen molecules to accelerate its production, and the other zymogens (inactive proteases) to produce chymotrypsin, elastase and carboxypeptidase

Question 4

What is the estimated protein content of both men and women?

Answer 4

Men = 16% total protein

Women = 14% total protein

(This is partly due to the fact that women have a higher amount of adipose tissue than men)

Question 5

What are the effects of exercise on protein synthesis and breakdown post exercise without protein ingestion?

Answer 5

Both protein synthesis and breakdown increase, but breakdown increases more, resulting in a negative net balance

Question 6

What are the effects of exercise on protein synthesis and breakdown post exercise with protein ingestion?

Answer 6

Both protein synthesis and breakdown increase, but protein synthesis increases more, resulting in a positive net balance

Question 7

What does the net balance of protein synthesis/degradation look like at rest in a fasted state?

Answer 7

Negative net balance, protein breakdown>protein synthesis

Question 8

What is the primary protein that initiates protein synthesis in muscle?

Answer 8

mTOR

mTOR phosphorylates several downstream proteins that iniate protein translation at the ribosome

Question 9

What is a ubiquitin ligase? What are the two key ubiquitin ligases in muscle?

Answer 9

A ubiquitin protein ligase is an enzyme that directs tagged proteins to the proteasome for degradation, and therefore, results in muscle atrophy after these enzymes are upregulated for a number of weeks

Two key ubiquitin ligases:

MuRF1
MAFbx

Question 10

What is the difference between a proteasome and a protease?

Answer 10

A proteasome is a protein complex that hydrolyzes other proteins through proteolysis (breaking peptide bonds) into smaller peptides

A protease hydrolyzes these smaller peptides into amino acids/single peptides

Question 11

What is ubiquitin?

Answer 11

Ubiquitin is a polypeptide that when attached to proteins, renders them recognizable to proteasomes for degradation

Question 12

What is protein degradation?

Answer 12

Amino acids being broken down to produce energy!

Question 13

What is the first process to occur for all amino acids in degradation?

Answer 13

Amino acids discard their amino group (H3N), either as ammonium (deamination) or transfer their amino groups to a-ketoglutarate (transamination)

Thus, amino groups are either removed through deamination or transamination

Question 14

Which compound part of the citric acid cycle do amino acids transfer their amino groups to through transamination?

Answer 14

a-ketoglutarate

Question 15

What products are produced through transamination?

What products are produced through deamination?

Answer 15

Transamination products:

a-keto acid
Glutamate

Deamination products:

a-keto acid
ammonium

Question 16

What happens to Glutamate once formed through transamination?

Answer 16

Glutamate can discard its amino group and form a-ketoglutarate and ammonium in the process of oxidative deamination

OR

Alanine and a-ketoglutarate is produced when glutamate reacts with pyruvate through transamination (Alanine is the amino group recipient)

OR

Glutamate can be converted into glutamine through acquisition of another amino group

Question 17

What happens to a-keto acids produced through de/transamination?

Answer 17

a-keto acids are converted to intermediate compounds of carb and lipid metabolism and used for in the TCA cycle to produce ATP

Question 18

How is glutamine produced in amino acid degradation and what is its fate?

Answer 18

Glutamine is produced when glutamate reacts with ATP and accepts another amino group. Glutamine can then dispose of this amino group as ammonium in certain organs and tissues

OR

In the liver, glutamine disposes of its amino acid, where it is safely eliminated in the urea cycle. Through this deamination, glutamine is converted back into glutamate

Glutamine + ADP + Pi = Glutamate + ATP + NH4+

Question 19

How many amino acids are essential amino acids and what does this mean?

Answer 19

9 of the 20 amino acids are essential meaning that they must be consumed from diet to support protein synthesis

Question 20

What is a Branch Chain Amino Acid?

Answer 20

A BCAA is an amino acid that can bypass degradation in the liver and therefore can be oxidized fully in (mainly) skeletal muscle because it contains the branched-chain a-keto acid dehydrogenase complex

There are three in the essential amino acids:

Leucine, Isoleucine and Valine

Question 21

Which tissues have the highest rate of protein synthesis?

Answer 21

The liver and the pancreas have the highest turnover rate, as they are key regulators in human metabolism

Brain tissue has higher rates than skeletal muscle

Question 22

How are amino acids in the liver primarily used?

Answer 22

Amino acids in the liver are primarily used in gluconeogenesis to produce glucose

18 of the 20 amino acids are glucogenic

Question 23

How many of the 20 amino acids are ONLY ketogenic? (meaning they are used in fat oxidation)

Answer 23

Only 2 are solely ketogenic, but 4 are both ketogenic and glucogenic

Question 24

What two pathways does the liver use to produce glucose?

Answer 24

1. The Cori cycle
2. The Glucose-Alanine Cycle - Pyruvate from glycolysis forms the amino acceptor (transamination) to produce alanine. Alanine is then transported to the liver where it is converted to glutamate and pyruvate, the latter of which is used via gluconeogenesis and the TCA cycle to produce glucose, and then transported back to the working muscle

*The Cori cycle and the Glucose-Alanine cycle are the same except lactate is replaced with alanine in the latter

Question 25

What is the urea cycle and what are its four main steps?

Answer 25

The urea cycle ‘neutralizes’ toxic ammonia from deamination reactions of amino acid degradation

After ammonia’s conversion to Carbonyl phosphate (reaction with bicarbonate):

1. Carbonyl phosphate links with Ornithine to form Citrulline
2. Citrulline is converted to arginine succinate
3. Arginine succinate splits into arginine and fumarate
4. Arginine is hydrolyzed by arginase to form UREA

Question 26

At what point in exercise is plasma [amino acid] affected?

Answer 26

Exercise >2 hours - [amino acid] decrease roughly by 30%

Durations of roughly 60 minutes or less, [amino acid] is unaffected