amino acid catabolism

Question 1

what are the intracellular stages of metabolism

Answer 1

…

Question 2

amino acid degradation

Answer 2

> amino acids which are not used as building blocks are degraded - there is no storage for amino acids
liver is the major site of amino acid degradation
absorption
protein turnover

Question 3

absorption

Answer 3

proteolytic enzymes in stomach and intestine produce single amino acids and di and ti peptides , these are then absorbed into intestinal cells and released into blood for absorption by other tissues

Question 4

protein turnover

Answer 4

tightly regulated
takes place at different rates
-important for rapid changes
-damaged proteins have to be removed

Question 5

amino acids contain nitrogen

Answer 5

some also contain nitrogen in the side chain
>amino acid breakdown produces ammonia and ammonium ions
>ammonium ions are toxic at high concentrations
>build up of these can lead to severe problems
>need a safe way of excreting excess nitrogen

Question 6

what are some of the major nitrogen-containing excretory molecules

Answer 6

urea
uric acid
creatinine
ammonium ions

Question 7

describe the synthesis of urea

Answer 7

there are three steps -
transamination
de-amination
urea cycle

Question 8

transamination

Answer 8

aminotransferase move the amino group from alpha amino acids to alpha keto acids
-usually an alpha hetoglutarate - a TCA intermediate, gives glutamate, occurs in all tissues
>for transport to the liver … the amino group of glutamate is transferred to pyruvate, giving alanine or glutamine synthase adds ammonium ions to glutamate giving glutamine
>alanine and glutamine are major carriers of nitrogen in the blood to liver

Question 9

deamination/urea cycle

Answer 9

> occurs in the liver
amino group of glutamate is converted to free ammonium ion
urea is synthesised in a complex series of reactions
-urea/ornithine cycle
-one nitrogen from free ammonium, the other from aspartic acid
-carbon from carbon dioxide

Question 10

synthesis of urea

Answer 10

simplified image

Question 11

urea cycle stoichiometry

Answer 11

CO2 + NH4+ + 3 ATP + aspartate + 2 H2O
»»» urea + 2 ADP + 2 Pi + AMP + PPi + fumarate

Fumarate is generated as an end-product in the cytosol.

Its conversion to malate enables its carbon to be transported back to the mitochondrial matrix via the malate-aspartate shuttle.

Question 12

degradation of carbon skeletons

Answer 12

after removal of alpha amino group the remaining carbon skeletons are converted into major metabolic intermediates
Can be converted to glucose or oxidised in the TCA cycle
>Ketogenic amino acids:
degraded to acetyl-CoA or acetoacetyl-CoA
can give rise to ketone bodies or fatty acids
>Glucogenic amino acids:
degraded to pyruvate or TCA cycle intermediates
can be converted into phosphoenolpyruvate and then into glucose

Question 13

glucogenic and ketogenic amino acids

Answer 13

… this slide again

Question 14

inherited disorders and amino acid degradation

Answer 14

alcaptonuria
maple syrup urine disease
phenylketonuria

Question 15

alcaptonuria

Answer 15

degradation of phenylalanine and tyrosine is blocked

Question 16

maple syrup urine disease

Answer 16

degradation of valine, isoleucine and leucine is blocked

• urine smells like maple syrup
• mental and physical retardation
• prevented by appropriate diet

Question 17

phenylketonuria

Answer 17

phenylalanine accumulates in all body fluids

• leads to severe mental retardation if untreated
• therapy - low phenylalanine diet

Question 18

urea cycle disorders

Answer 18

defect in a urea cycle enzyme …
so there could be an accumulation of urea cycle intermediates which leads to increased levels of glutamine levels in the circulation, alpha-ketoglurarate is no longer regenerated,
alpha-ketoglurarate levels become too low to fix more free ammonium ion
…and elevated levels of ammonium in the blood are toxic for the nervous system

> treatment is with low protein diet and drugs which remove nitrogen
ie forming complexes with amino acids which are excreted - gene therapy in hepatocytes