Amino acid synthesis and degradation

Question 1

Examples of catabolism in body

Answer 1

Energy yielding nutrients (fats, carbs, proteins) –> energy poor end products (H2O, CO2, NH3)
-gives off chemical energy (ATP, NADPH)

Question 2

Examples of anabolism in body

Answer 2

Precursor molecules (amino acids, sugars, fatty acids, nitrogenous bases) --> cell macromolecules (proteins, polysaccharides, lipids, nucleic acids)
-requires chemical energy (ATP, NADPH)

Question 3

5 examples of essential amino acids

Answer 3

From diet

• Histidine
• Isoleucine
• Leucine
• Lysine
• Methionine

Question 4

Non-essential amino acids

Answer 4

Synthesised in body

• Alanine
• Aspargine
• Aspartate
• Glutamate
• Serine

Question 5

Conditionally essential amino acids

Answer 5

Synthesised in body
Not essential except in times of illness and stress
-Arginine
-Cysteine
-Glutamine
-Glycine
-Proline
-Tyrosine

Question 6

Amino acid synthesis

Answer 6

9 non-essential amino acids are made from glucose + N source (amino acid or ammonia)
Non essential AAs can also be made from essential AAs
-Methionine donates S for cysteine
-Phenylalanine forms tyrosine

Question 7

Protein digestion

Answer 7

• ingested protein broken down in stomach and small intestine
• proteolytic enzymes (proteases)
• AAs absorbed into epithelial cells and enter blood
• active transport into cells

Question 8

AAs derived from intermediates of glycolyss

Answer 8

Serine, glycine, cysteine, alanine

Question 9

AAs related to TCA cycle intermediates

Answer 9

Aspartate - oxaloacetate (reversible) –> Aspargine, Methionine, Threonine, Lysine
α-ketoglutarate –> glutamate –> Glutamine, Proline, Arginine

Question 10

When does amino acid degradation occur

Answer 10

Excess can neither be stored or excreted
Sources: during normal synthesis and degradation some is no longer needed i.e. when diet exceeds need
Proteins can act as energy source during fasting
Some AAs return to precursors, others not

Question 11

Define glucogenic degradation

Answer 11

Carbons converted to glucose (some are both)

Question 12

Define ketogenic degradation

Answer 12

Converted to acetyl CoA or acetoacetate (ketone bodies)

-some are both keto- and glucogenic

Question 13

Where does AA degradation take place

Answer 13

Liver

Question 14

Products of AA degradation

Answer 14

Carbon - glucose
CO2
Acetyl CoA
Acetoacetate

Question 15

What happens to nitrogen after AA degradation

Answer 15

1. Removal of α amino gp - transaminases/ amino transferases
2. Formation of ammonia
3. Urea cycle

Question 16

Define transamination

Give example

Answer 16

Amino gp from one amino acid transferred to another

• α ketoglutarate and glutamate usually a pair (cofactor is pyridoxyl phosphate, derived from vit. B6)
• reaction is reversible (involved in synthesis and degradation)

Question 17

Removal of amino acid nitrogen as ammonia

Answer 17

Glutamate can collect nitrogen from other amino acids
This is converted to ammonia by glutamate dehydrogenase in liver mitochondria
Ammonia enters urea cycle

Question 18

Protein degradation

Answer 18

Proteins continuously synthesised and degraded at different rates
Proteins recycled within cells

Question 19

Lysosomes

Answer 19

protease filled vesicles

Question 20

Ubiquitin

Answer 20

Small proteins that target proteins for degradation

Question 21

Proteasome

Answer 21

Protease complex, protein is unfolded and degraded using ATP

Question 22

Nitrogen and bio systems

Answer 22

N2 not usable in biological systems
NH3 usable and crosses membranes
NH4+ toxic

Question 23

What is used by organisms to excrete nitrogen?

Answer 23

Ammonia, uric acid and urea

Question 24

Nitrogen balance

Answer 24

Nitrogen ingested (dietary proteins) = nitrogen excreted

Question 25

Nitrogen balance for children, pregnant, disease, starving

Answer 25

Children & pregnant: +N balance

Disease/ starvation: -N balance

Question 26

Where do the steps of urea cycle take place

Answer 26

First 2 in mitochondrion

Other 3 in cytosol

Question 27

How does nitrogen enter urea cycle

Answer 27

Enters as NH4+ and aspartate

Question 28

What initiates the urea cycle

Answer 28

Ornithine, is regenerated afterwards

Question 29

Control of urea cycle

Answer 29

‘Feed forward’ regulation: higher the rate of ammonia production, higher the rate of urea
Allosteric activation of enzymes (arginine stimulates carbamoyl phosphate synthase)
High protein diet or fasting induces urea cycle enzymes –> frequent urination

Question 30

Tissues (precise reactions and location depends on physiological state - fed or fasting)

Answer 30

Fasting: muscle protein broken down to AAs
Alanine (from pyruvate in muscles) and glutamine (mops up nitrogen) enter blood
These are broken down to glucose and ketone bodies in liver and used for energy

Question 31

Ketone bodies when low glucose

Answer 31

Reconverted to acetyl CoA and enter TCA cycle for energy when glucose is low

Question 32

2 examples of ketone bodies

Answer 32

Acetoacetate, beta hydroxybutyrate

Acetoacetate spontaneously breaks down to acetone

Question 33

What gives rise to ‘fruity’ smell of breath

Answer 33

Ketotic states (energy coming from ketone bodies)

Question 34

pH of ketone bodies

Answer 34

Acidic –> can lead to ketoacidosis

Question 35

Inborn errors of AA metabolism

Answer 35

• deficient enzymes in AA metabolism lead to accumulation of harmful products
• Phenylketonuria: mutation in phenylalanine hydroxylase, mental retardation
• urea cycle disorders: accumulation of ammonia, toxic to NS

Question 36

Jesse Gelsinger

Answer 36

1981-1999

• urea cycle disorder: ornithine transcarbamylase deficiency
• inability to metabolise ammonia
• first person to die as result of gene therapy clinical trial (adenoviral vector)