Protein Breakdown & Urea Formation

Question 1

Quantitatively how does growth occur?

Answer 1

Growth = Synthesis - Breakdown

We synthesise and breakdown an equal amount of protein everyday

Question 2

How are Proteins stored?

Answer 2

They don’t have any specific store as they are either structural or functional
Excess proteins are broken down and excreted

Question 3

How is Nitrogen transferred into Urea?

Answer 3

1. transamination
2. NH3 formation
3. Urea formation

Question 4

Give examples α-ketoacids

Answer 4

• α-ketogluterate
• oxaloacetate
• pyruvate

Question 5

What is the fate of the NH3 produced in oxidative deamination?

Answer 5

Used as the substrate for Urea Cycle

Question 6

What is the fate of the Nitrogen released in amino acid breakdown?

Answer 6

Nitrogen is toxic so is removed safely

Question 7

How is nitrogen transported out the body?

Answer 7

Glutamate accepts Nitrogen forming glutamine

Glutamine then is the main transporter of Nitrogen

Question 8

How does transamination and oxidative deamination integrate to prodcue NH3?

Answer 8

Amino acids transfer their α amino group to α-ketogluterate
α-ketogluterates transfer the amino group to glutamate
glutamate dehydrogenased to produce NH3

Question 9

Outline the reaction that occurs to produce glutamine

Answer 9

Glutamate + ATP + NH4+ Glutamine + ADP

Question 10

What are the two major transaminases involved in Urea formation?

Answer 10

ALT - alanine

AST - aspartate

Question 11

Why does the urea cycle only occur in the liver and not in muscles?

Answer 11

The enzymes required for the urea cycle to occur are only present in the liver and not in the muscles

Question 12

How are the reactants reformed from the products by AST?

Answer 12

AST funnels amino groups from glutamate product to oxaloacetate to form aspartate

Question 13

What part of the urea cycle occurs in the mitochondria?

Answer 13

HCO3- + NH4+ –> Carbamoyl phosphate
carbamoyl phosphat enters the cycle in the cytoplasm as its converted to Citruline
Transamination of oxaloacetate -> aspartate

Question 14

What is the fate of amino acids consumed in the diet?

Answer 14

Amino acids taken up in diet and released via the break down of proteins for energy

Question 15

How are amino acids used in muscles?

Answer 15

During prolonged exercise or starvation branched amino acids are used for energy

Question 16

What are α-ketoacids?

Answer 16

Organic compounds containing a carboxylic acid group and a ketone group

Question 17

Glutamine can donate Nitrogen for the biosynthesis of which molecules?

Answer 17

• amino acids
• nucleotides
• amino sugars
• NAD+

Question 18

What is the significance of the carbon skeleton of an amino acid?

Answer 18

Carbon skeletons are involved in energy metabolism and biosynthetic pathways

Question 19

What happens to the Nitrogen released in muscles via amino acid breakdown?

Answer 19

Urea cycle enzymes aren’t present
Two routes can be taken to excrete N to the liver
1. ALANINE
- N transferred to alanine via glutamate + pyruvate
(oxidative deamination)

2. GLUTAMATE
   
   • produce glutamine to transport N

Question 20

What is the role of the transaminases in the transamination process?

Answer 20

They transfer and amino group from an amino acid to the α-ketoacid

Question 21

How is the Nitrogen balance maintained in the body?

Answer 21

Via the positive and negative protein balance

Question 22

What is the consequence of protein breakdown?

Answer 22

When proteins are broken down, NH3 ammonia is produced which is toxic

Question 23

What is the Urea cycle?

Answer 23

The urea cycle is the means of excreting toxic Nitrogen from our bodies via urine

Question 24

Outline how ammonia is transported from peripheral tissue to the liver via the Glucose alanine cycle

Answer 24

1. Glucose transported from the liver to the muscle (or
   glycogen converted to glucose in muscle)
2. glucose converted to pyruvate (glycolysis)
3. pyruvate -> alanine using NH4+ from the breakdown of
   branched A.A
4. Alanine transpirted back to liver and converted to
   (pyruvate -> glucose) or (glutamate -> urea)

Question 25

Outline the conversions carried out by ALT and AST in transamination

Answer 25

ALT: alanine + α-ketogluterate pyruvate + glutamate AST: aspartate + α-ketogluterate oxaloacetate + glutamate These reactions are fully reversible

Question 26

What is the positive protein balance?

Answer 26

Positive protein balance is when Input > Output

Question 27

Where are the substrates needed for the Urea cycle obtained from?

Answer 27

The urea cycle substrates are released from glutamine (O=C-(NH2)2)

Question 28

What is a negative protein balance caused by?

Answer 28

- Wasting diseases - Burns - Trauma - Response to Catabolic hormones (lack of anabolic homrones) e.g. diabetes

Question 29

What are the 2 major parts of an amino acid?

Answer 29

- Carbon skeleton | - Nitrogen

Question 30

Explain how transamination occurs

Answer 30

1. Amino acid A reacts with α-ketoacid b 2. Amino acid A converted to α-ketoacid A 3. ammonia group transferred to α-ketoacid to produce Amino acid b

Question 31

Where does oxidative deamination occur?

Answer 31

Mitochondrial matrix

Question 32

What causes a positive protein balance?

Answer 32

- growth - pregnancy - exercise and tissue hypertrophy - response to anabolic hormones

Question 33

How are amino acids metabolised?

Answer 33

Unlike carbohydrates & fats, amino acids are either used or broken down but not stored

Question 34

Where do transaminases mainly function?

Answer 34

Predominantly carry out transaminations in the liver

Question 35

Where in the hepatocytes does the urea cycle occur?

Answer 35

Occurs in the mitochondria and cytoplasm

Question 36

What happens to free NH3 that is normally produced in tissues?

Answer 36

Free ammonia generated in tissues combine with glutamate to give glutamine using glutamine synthase enzyme

Question 37

How is the transamination process regulated?

Answer 37

Transamination is regulated by transaminases (aminotransferases)

Question 38

What are the substrates required for the urea cycle?

Answer 38

- Bicarbonate HCO3- - Aspartate AST - Ammonium Ions NH4+

Question 39

How is ammonia formed from the products of transamination?

Answer 39

Via Oxidative Deamination Glutamate can form NH3 directly using glutamate dehydrogenase in a reversible reaction using NAD (degradation) or NADP (synthesis)

Question 40

What is the fate of the citruline once in the cytoplasm?

Answer 40

Converted to Argininosuccinate 2 routes taken: 1. argininosuccinate -> arginine -> urea (via arginase enzyme) 2. argininosuccinate -> fumurate -> malate -> oxaloacetate -> aspartate (via transamination of A.A -> α-ketoacid) cycle repeats

Question 41

How much Nitrogen is present in biological compounds Urea and Proteins?

Answer 41

Urea contains 48% Nitrogen by weight Protein contains 16% Nitrogen by weight => 1g Urea formed from 3g of Protein

Question 42

Despite being fully reversible, which reactions of ALT and AST are favoured by their respectable equilibrium's?

Answer 42

ALT equilibrium favours pyruvate formation AST equilibrium favours the generation of aspartate and α-ketogluterate

Question 43

How is Nitrogen removed from the body?

Answer 43

In mammals, Nitrogen is converted to neutral non toxic Urea compound which is then excreted in urine

Question 44

What is meant by a negative protein balance?

Answer 44

When the Nitrogen Input < Output

Question 45

How are AST and ALT used to detect liver damage?

Answer 45

High levels of AST and ALT in the blood can indicate liver damage

Question 46

Which amino acids are exempt from undergoing transamination?

Answer 46

Threonine | Lysine

Question 47

What are the products of amino acid breakdown?

Answer 47

amino acid --> α- ketoacid + NH3