L17 Post-Absorption Processing of Proteins

Question 1

What can amino acids be used for in the body?

Answer 1

Amino acids are used to:
- Synthesise proteins
- Synthesis other nitrogen containing metabolites
- Energy (ATP) - use the carbon skeleton to enter the Kreb’s cycle or convert them to other things for storage or use: such as fatty acids and ketone bodies (under starvation)
Glucose/glycogen

Question 2

What is glycine used to synthesise?

Answer 2

Haem

Question 3

What is tyrosine used to synthesise?

Answer 3

Dopamine, Noradrenaline and Adrenaline

Question 4

What is tryptophan used to synthesise?

Answer 4

Serotonin

Question 5

Which amino acid(s) is histamine synthesised from?

Answer 5

Histidine

Question 6

Which amino acid(s) is creatine synthesised from?

Answer 6

Glycine and Arginine

Question 7

Which amino acid(s) are purine bases synthesised from?

Answer 7

Glycine, Aspartate and Glutamine

Question 8

Why do malnourished children have central abdominal swelling and lower limb oedema?

Answer 8

• Abdominal bloating - central oedema due to lack of albumin. Also swollen lymph nodes as they manufacture triacylglycerols that they cannot export without proteins to form lipoproteins. Fats tend to be retained in the liver in this situation.
  
  • Lower limb oedema - Due to poor circulation. The blood is not flowing through fast enough to make the balance between tissue and blood fluid. This is down to a lack of albumin.

Question 9

What is the effect of hyperammonaemia?

Answer 9

Tremor, vomiting, cerebral oedema, coma and death

Question 10

What are the three stages involved in disposal of ammonia in the liver?

Answer 10

1. Transamination
2. Deamination
3. Urea cycle

Question 11

What is ammonia transported to the liver as?

Answer 11

Glutamine or Glutamate

Question 12

Give details of transamination.

Answer 12

ransamination – transfer of amino group from amino acid to a- ketoglutarate forming glutamate (in most tissues) and a keto acid (which can enter the Kreb’s cycle). Amino acid break down occurs in all tissues.

Question 13

Give details of deamination.

Answer 13

Glutamate is converted back to a-ketoglutarate releasing ammonia. This requires NAD(P) and water. The deamination step occurs in the mitochondria. The enzyme that picks up the ammonia is found in mitochondria. This enzyme is Carbamoyl phosphate synthetase 1. It combines ammonia and bicarbonate to form carbamoyl phosphate using 2 ATP.

Question 14

What is the control step in urea synthesis?

Answer 14

Carbamoyl phosphate formed from ammonia and bicarbonate.

Question 15

Where does urea synthesis occur?

Answer 15

In the mitochondrial matrix and the cytosol.

Question 16

Give the details of urea synthesis.

Answer 16

Takes place partly in the mitochondria matrix and partly in the cytosol. Carbamoyl phosphate then comes in and reacts with ornithine. Ornithine and citrulline are also alpha-amino acids. Ornithine is converted to citrulline by the addition to carbamoyl phosphate. This is where one of the ammonia groups from urea comes from. The second comes from aspartate. Aspartate joins with citrulline once it has moved into the cytosol, to form Arginosuccinate. ATP is required. Fumarate is the keto acid - the remainder of the aspartate. This leads the amino group from aspartate to form arginine. Finally arginine is hydrolysed and urea is released.

Question 17

What is uric acid?

Answer 17

Uric acid is derived from purine nucleotides rather than protein. Not to be confused with urea.
Excess uric acid in the blood (hyperuricaemia) can lead to deposition of sodium urate crystals in the kidneys (kidney stones) and in the joints (gout - where uric acid crystallises in the joint, causes inflammation and extreme pain). Very often gout is presented in the big toe.

Question 18

What is the skeleton of amino acids used for?

Answer 18

• Kreb’s cycle to produce ATP and more NADH and FADH
  
  • Fatty acid and ketone synthesis
    Glucose synthesis in gluconeogenesis - however not every amino acids are glucogenic i.e. cannot be made into glucose.

Question 19

Which amino acids are ketogenic?

Answer 19

Lysine and Leucine

Question 20

Where does gluconeogenesis occur?

Answer 20

Gluconeogenesis takes place mainly in the liver and, to a lesser extent, in the cortex of the kidneys.

Question 21

Which steps are different in gluconeogenesis compared to glycolysis?

Answer 21

Much of glycolysis is reversible so the enzymes can be used in gluconeogenesis. There are 3 irreversible steps:

- Conversion of glucose to glucose-6-phosphate via hexokinase 
- Conversion of fructose-6-phosphate to fructose-1,6-bisphosphate via phosphofructokinase 
- Conversion of phosphoenolpyruvate to pyruvate via pyruvate kinase

Question 22

How is pyruvate converted to phosphoneolpyruvate?

Answer 22

The conversion of pyruvate to phosphoenolpyruvate (PEP) to pyruvate requires 2 steps and goes through oxaloacetate. Oxaloacetate from the Kreb’s cycle can move out into the cytosol for gluconeogenesis.

Pyruvate to PEP is most complex step – pyruvate is converted in the mitochondria to oxaloacetate by pyruvate carboxylase. The oxaloacetate (OAA) can’t leave the mitochondria so is converted to malate or asparate, diffuses out of mitochondria, and is reconverted to OAA in the cytosol. OAA is then converted to PEP by PEP carboxykinase which removes the carbon dioxide leaving us with PEP.

Question 23

How is Fructose-1,6-bisphosphate converted to fructose-6-phosphate?

Answer 23

Fructose-bisphosphatase

Question 24

How is Glucose-6-phosphate converted to glucose?

Answer 24

Glucose-6-phosphatase

Question 25

What are the controls of gluconeogenesis?

Answer 25

It is allosterically inhibited by AMP (cannot make glucose if the cell is short of energy) and activated by citrate (high levels of citrate indicate high levels of Kreb’s activity and so a signal of high levels of energy). It is activated by glucagon and inhibited by insulin. Activated by acetyl CoA and inhibited by ADP.

Question 26

Why do blood glucose levels rise in type 1 diabetes?

Answer 26

Glycolysis is inhibited (also remember that insulin is needed to allow glucose entry to muscle and adipose tissue and so there is low glucose in the cell).
Blood glucose levels rise

Gluconeogenesis is stimulated
The liver synthesises and releases glucose into the circulation as in the absence of insulin, the body perceives starvation. Raised blood glucose may be so high it may cause someone to enter a coma and die in uncontrolled diabetes.
Blood glucose levels rise further!

Question 27

What is the Cori cycle?

Answer 27

The Cori Cycle refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is cyclically.

Question 28

Why does alcohol make you hungry?

Answer 28

Alcohol is metabolised in the liver and large amounts of NADH are produced. This NADH inhibits gluconeogenesis. Blood sugar then drops leading to hunger. This is as normally alanine is converted to pyruvate into glucose. In the presence of large amounts of NADH, a lot of the pyruvate is converted to lactate. The alanine is therefore not turned into glucose. In the presence of high amounts of NADH, the reversible reaction is going towards lactate not towards pyruvate.

You could otherwise use convert glycerol or glycerol phosphate to convert it to glyceraldehyade-3-phosphate. This reaction however requires NAD+, which is unavailable due to the high amounts of NADH.

All the ways you would normally make glucose are blocked due to the high amounts of NADH.

Question 29

Why do malnourished children have poor skin condition and poor nutrient absorption?

Answer 29

Epithelial cells turn over quickly and so if you cannot synthesis new cells quickly there are problems with healing and skin condition. Epithelial cells also line the gut and so this leads to problems with absorption.

Question 30

What is Kwashiorkor?

Answer 30

The name means ‘disease of the first child when the second is born.’
Because children develop it once they are weaned off breast milk – onto low protein diet, often high in fibre which is hard to digest. Kwashiorkor is a form of severe protein malnutrition characterised by oedema and an enlarged liver with fatty infiltrates. It is caused by sufficient calorie intake, but with insufficient protein consumption.

Question 31

How is free ammonia in the muscles or peripheral tissue mopped up?

Answer 31

If there is any free ammonia in the muscles or peripheral tissues, it can be mopped up and converted to glutamine. Further addition of another group to form glutamine. Glutamine can then be transported to the liver and converted to glutamate, which is then broken down to alpha-ketoglutarate.

Question 32

What is required for transamination?

Answer 32

Transfer of amino group from amino acids to a-ketoglutarate to form glutamate: requires pyridoxal phosphate (B6) as a cofactor. The conversion of glutamate to alpha-ketoglutarate the deamination step and requires NAD or NADP as it is a dehydrogenase enzyme.