Amino acid catabolism

Question 1

3 situations in which amino acids are catabolised

Answer 1

-normal synthesis and degredation of proteins -when protein is in excess in the diet -during starvation

Question 2

Ultimate purpose of amino acid catabolism

Answer 2

remove the amino group and use the carbon skeleton for TCA or to make gluconeogenic precursors to feed to the rest of the body

Question 3

Where are amino acids processed ?

Answer 3

Liver`

Question 4

What happens to the amino groups in amino acids when catabolised ?

Answer 4

They are either recycled, or converted and excreted

Question 5

How are nitrogen groups from amino acid catabolism ‘passed around’ in the liver ?

Answer 5

They are added to α-ketogluterate to form glutamate (or glutamine). Glutamate is then sent to the liver mitochondria where it is given up and becomes NH4+

Question 6

In the muscle, what happens to the extra amino groups ?

Answer 6

They are added to pyruvate in order to become alanine, which is transported to the liver

Question 7

What converts pepsin to pepsinogen

Answer 7

The acid of the stomach

Question 8

What happens to excess amino acids ?

Answer 8

they are NOT stored, they are either used for protein synthesis or used for energy The rest are excreted, which is why high protein diets put strain on the kidneys

Question 9

Where does pepsin cleave ?

Answer 9

F,W,Y

Question 10

What are the pancreatic proteases:

Answer 10

trypsin, chymotrypsin, carboxypeptidases A and B

Question 11

Where do the pancreatic proteases cleave ?

Answer 11

they cleave short peptides into free amino acids

Question 12

difference between ketogenic and glucogenic amino acids

Answer 12

Glucogenic amino acids make oxaloacetate to form glucose Ketogenic amino acids make acetyl CoA or acetoacetyl CoA to form ketones

Question 13

amino groups are transformed into one of these three groups in this organ

Answer 13

they are turned into a non-toxic, water soluble product (urea, uriv acid, ammonium) in the liver

Question 14

Transamino reaction

Answer 14

α ketogluterate + L-amino acid –> L-glutamate +α-keto group (catalysed py pyridoxal phosphate (PLP))

Question 15

How is the amino group removed from glutamate in the liver ?

Answer 15

It uses glutamate dehydrogenase, which catalyses the oxydative deamanation of glutamate

NAD or NADP can be used under different conditions

Question 16

How are pyruvate and alanine interconverted ?

Answer 16

In the muscle, pyruvate gets an amino group from glutamate and becomes alanine
This reaction is catalysed by alanine aminotransferase

The alanine is transferred through the blood to the liver, where the reaction occurs in reverse

(glucose-alanine cycle)

Question 17

What happens to glutamine when it enters the hepatic mitochondria ?

Answer 17

The amino groups are turned into NH₄⁺and passed off to carbomoyl phosphate (or aspartate).

The carbomyl phosphate is then put into the urea cycle

Question 18

enzymes of the urea cycle (4)

Answer 18

1. Ornithine Transcarbamoylase
2. Arginosuccinate Synthetase
   3 Arginosuccinase
3. Arginase

Question 19

What is put into the urea cycle, and what comes out ?

Answer 19

An -NH₂ group is added by carbomyl phosphate, and aspartate is added in step 2b

Fumerate and urea are the products

Question 20

Regulation of the urea cycle

Answer 20

activated (allosterically) by acetyl CoA, glutamate, and arginine

Question 21

How is the fumerate from the urea cycle added to the TCA cycle ?

Answer 21

It is converted into malate in the cytosol, which enters the mitochondria and is added to the TCA cycle

Question 22

You are a bodybuilder and you boost your protein intake to maximize your bodybuilding capacity. What is the fate of excessive dietary protein or amino acid intake?

Answer 22

Building muscle requires some increase in amino acid intake, but not to the extent that many bodybuilders consume

As amino acids are not stored, they are sent to the liver to be catabolised into energy and may be used to make acetyl CoA (ketogenic) or oxaloacetate (glucogenic). Alternately, the carbon skeletons may enter directly into the TCA cycle.

As a result, more nitrogen must be excreted, which may put a strain on the kidneys over time.

Question 23

Some genetic diseases are caused by loss-of-function mutations of Urea Cycle enzymes. What would be the symptoms in humans lacking functional versions of these enzymes?

Answer 23

As the purpose of the urea cycle is to excrete nitrogen waste in a safe way, loss of function mutations in these enzymes would lead to a buildup of nitrogen products, detectable in the blood.

Accumulation may reach toxic levels in the brain, which lead to several neurological dysfunction, and eventually death.

Question 24

The enzyme: arginosuccinate synthetase uses both high-energy phosphate bonds of ATP, in the process generating pyrophosphate, PPi which is broken down by pyrophosphatase. Where have we encountered pyrophosphatase before in metabolic pathways?

Answer 24

Fatty acid -> fatty acyl CoA
UDP glucose production

Question 25

What is the function of SAM ?

Answer 25

S-Adenosyl methionine converts phosphatidyl ethanolamine to phosphadityl choline.

(swaps out an X group)

Question 26

What is Pterin ?

Answer 26

It is converted into vitamin B12, a coenzyme in many steps

It cannot be synthesized de novo

Question 27

What can be made from tryptophan catalysis (3)

Answer 27

Nicotinate (niacin) (precursor of NAD an NADP

Serotonin (neurotransmitter)

indoleacetate (plant growth factor)

Question 28

Is tryptophan ketogenic or glucogenic ?

Answer 28

Both

the ring can be used to make ketones
the alanine part can make oxaloacetate

Question 29

Glutamate -> glutamine regulation

Answer 29

End product regulation (see below)
Adenylation (addition of AMP)

Regulated enzyme:

Glutamine synthase

Question 30

What amino acid ca be synthesized by pyruvate ?

Answer 30

Alanine

Question 31

What are the main pecursors to make heme ? (2)

Answer 31

Succinyl CoA
Glycine

They make δ-aminolevulinate (main unit of Hb)

Can also make from glutamate, but rarely

Question 32

Describe the general synthesis of heme

Answer 32

Succynyl CoA and glycine make δ-aminolevulinate

δ-aminolevulinate units come together to make a porphyrin ring

Fe is added to the centre

Question 33

What happens to heme in a bruise ?

Answer 33

Heme has its iron removed and is synthesized into biliverdin by heme oxygnease

Biliverdin is then reduced to bilirubin by biliverdin reductase (uses NADPH)

The bilirubin is then excreted

(iron is the last step of synthesis, first step of breakdown)

Question 34

What is glutathione, how is it made, and what does it do ?

Answer 34

It is a tripeptide (γ-glu - cys - gly) that protecs the cell from oxidative damage

2 of them dimerize via disulphide bridge, and the hydrogen atoms are used to satisfy the free radicals

Question 35

How many precursors are involved in the synthesis of a purine ring ?

Answer 35

6

Question 36

Write a short note on glutamate metabolism and its role in general amino acid metabolism.

Answer 36

Glutamate is synthesized by adding an amino group to α-ketogluterate through a transaminase reaction. A second amino group can be added to for glutamine.

These amino groups come from other amino acids that are being metabolised. The glutamate and glutamine provides a safe way to transport nitrogen to the kidneys for disposal.

Question 37

Explain why phenylalanine is both ketogenic and glucogenic

Answer 37

The ring structure can be used to make acetyl CoA (ketogenic), while the carbon skeleton of the ‘alanine’ part can be used to make oxaloacetate (glucogenic)

Question 38

Outline the pathway for the conversion of ammonia to urea

Answer 38

The nitrogen transported via glutamine / glutamate is added to carbamoyl phosphate

It is then transported out of the mitochondria, and enters the urea cycle

A second amino group is added by aspartate in step 2 of the urea cycle

The end products of the cycle are urea and fumerate

Question 39

Explain the alanine-glucose cycle

Answer 39

In the muscle, pyruvate gets an amino group from glutamate and becomes alanine
This reaction is catalysed by alanine aminotransferase

The alanine is transferred through the blood to the liver, where the reaction occurs in reverse

The resulting pyruvate is synthesized into glucose by the liver for distribution, and the glutamate passes off the amino group into the urea cycle

Question 40

Which of the following statements are CORRECT:

1. The two nitrogens of urea are derived directly in the biosynthetic pathway from ammonia.
2. The correct sequence of intermediates in the urea cycle is: carbamoyl phosphate, citrulline, arginosuccinate, arginine, ornithine, fumarate
3. Glutamate dehydrogenase can use either NADH or tetrahydrobiopterin as reducing cofactors.
4. The decarboxylation of tryptophan produces histamine.
5. The precursors for heme biosynthesis are glycine and succinyl CoA

Answer 40

1. Incorrect; the nitrogens come from glutamate (via carbomyl phopshate) and alanine
2. Incorrect. Carbomyl phosphate adds a nitrogen gtoup to ornitine to become citrulline;
   Fumerate is a product (arginosuccinate -> fumerate + arginine)
3. Incorrect. It can use NADP, or NAD, but not tetrahydrobiopterin
4. Incorrect. Histamine comes from histidine
5. True