Metabolism of amino acids

- exercise -

Vladimíra Kvasnicová

Choose essential amino acids

a) Asp, Glu

b) Val, Leu, Ile

c) Ala, Ser, Gly

d) Phe, Trp

Choose essential amino acids

a) Asp, Glu

b) Val, Leu, Ile

c) Ala, Ser, Gly

d) Phe, Trp

Essential amino acids

1) branched chain: Val, Leu, Ile

2) basic: His, Arg, Lys

3) aromatic: Phe (→ Tyr), Trp

4) sulfur-containing: Met (→ Cys)

5) other: Thr

„10“

Choose amino acids from which the other amino acid can be synthesized in a human body

a) valine → leucine

b) aspartate → asparagine

c) phenylalanine → tyrosine

d) methionine + serine → cysteine

Choose amino acids from which the other amino acid can be synthesized in a human body

a) valine → leucine leucine is the essential AA

b) aspartate → asparagine

c) phenylalanine → tyrosine

d) methionine + serine → cysteine

Synthesis of

ASPARAGINE

needs glutamine as

–NH2 group donor

(it is not ammonia as in the Gln synthesis)

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)

Synthesis of Tyr from Phe

The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)

Synthesis of Cys from Met and Ser

The amino acids can be formed from the citrate cycle

intermediatesin a human body

a) a-ketoglutarate → glutamate

b) succinyl-CoA → isoleucine

c) oxaloacetate → aspartate

d) malate → threonine

The amino acids can be formed from the citrate cycle

intermediatesin a human body

a) a-ketoglutarate → glutamate

b) succinyl-CoA → isoleucine Ile is the essential AA

c) oxaloacetate → aspartate

d) malate → threonine Thr is the essential AA

The figure is from http://www.tcd.ie/Biochemistry/IUBMB-Nicholson/gif/13.html (Dec 2006)

Amphibolic character

of citrate cycle

The compound(s) can be synthesized from the amino acid

a) tyrosine → serotonin

b) serine → ethanolamine

c) tryptophan → catecholamines

d) cysteine → taurine

The compound(s) can be synthesized from the amino acid

a) tyrosine → serotonin Tyr → catecholamines

b) serine → ethanolamine formed by decarboxylation

c) tryptophan → catecholamines Trp → serotonin

d) cysteine → taurine

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

taurin is used in conjugation reactions in the liver

– it is bound to hydrophobic substances to increase their solubility

(e.g. conjugation of bile acids)

If the amino acid is metabolised the substance is formed:

a) methionine gives homocysteine

b) serine gives glycine and folic acid derivative: methylene tetrahydrofolate

c) glutamine releases ammonia

d) some amino acides can be degraded to acetoacetate

If the amino acid is metabolised the substance is formed:

a) methionine gives homocysteine

b) serine gives glycine and folic acid derivative: methylene tetrahydrofolate

c) glutamine releases ammonia

d) some amino acides can be degraded to acetoacetate = one of ketone bodies

The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)

B12

Regeneration of Met

(vitamins: folate+B12)

The figure is from http://www.biocarta.com/pathfiles/GlycinePathway.asp (Jan 2007)

Synthesis of serine and glycine

glycolysis

Choose products of the transamination reactions

a) alanine → pyruvate

b) glutamate → 2-oxoglutarate

c) aspartate → oxaloacetate

d) phenylalanine → tyrosine

Choose products of the transamination reactions

a) alanine → pyruvate

b) glutamate → 2-oxoglutarate

c) aspartate → oxaloacetate

d) phenylalanine → tyrosine it is not transamination

The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)

Transamination reaction

! REVERSIBLE !

enzymes: amino transferases

coenzyme: pyridoxal phosphate (vit. B6 derivative)

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

alanine aminotransferase

(ALT = GPT)

aspartate aminotransferase

(AST = GOT)

Amino transferases important in medicine („transaminases“)

Amino nitrogen released from carbon sceletons of AAs can be transported in

blood as

a) NH4+

b) alanine

c) glutamine

d) urea

Amino nitrogen released from carbon sceletons of AAs can be transported in

blood as

a) NH4+ physiologically up to 35 µmol/l (NH3 + H + NH4

+)

b) alanine formed by transamination from pyruvate

c) glutamine the most important transport form of –NH2

d) urea it is the end product of degradation of amino nitrogen (liver → kidneys → urine)

Transport of amino nitrogen

from degraded muscle proteins

productsexcreted

with urine

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss,

Inc., New York, 1997. ISBN 0‑471‑15451‑2

Glucose-alanine cycle

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

alanine transfers both the carbon

sceleton for gluconeogenesis and –NH2 group

glutamine synthetase

GLUTAMINE

= the most important transport form af amino nitrogen in

blood

it transfers two amino groups released by degradation of AAs

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

Choose glucogenic amino acids

a) alanine

b) lysine

c) leucine

d) glutamine

Choose glucogenic amino acids

a) alanine

b) lysine

c) leucine

d) glutamine

7 degradation products of AAs

1. pyruvate Gly, Ala, Ser, Thr, Cys, Trp

2. oxaloacetate Asp, Asn

3. a-ketoglutarate Glu, Gln, Pro, Arg, His

4. succinyl-CoA Val, Ile, Met, Thr

5. fumarate Phe, Tyr

6. acetyl-CoA Ile

7. acetoacetyl-CoA Lys, Leu, Phe, Tyr, Trp

glucogenic AAs

ketogenic AAs

Glutamate dehydrogenase (GMD)

a) catalyzes conversion of Glu to oxaloacetate

b) is found in mitochondria of hepatocytes

c) produces ammonia

d) needs pyridoxal phosphate as a coenzyme

Glutamate dehydrogenase (GMD)

a) catalyzes conversion of Glu to oxaloacetate

b) is found in mitochondria of hepatocytes

c) produces ammonia

d) needs pyridoxal phosphate as a coenzyme

The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)

GLUTAMATE DEHYDROGENASE

removes amino group from carbon sceleton of Glu in the liver

1. –NH2 from AAs was transfered by transamination → Glu

2. free ammonia is released by oxidative deamination of Glu

Choose correct statement(s) about metabolism of amino acids

a) alanine aminotransferase (ALT) transforms pyruvate to alanine

b) aspartate aminotransferase (AST) transforms aspartate to a-ketoglutarate

c) glutamine synthetase transforms glutamate to glutamine

d) glutaminase catylyzes conversion of glutamine to ammonia and a-ketoglutarate

Choose correct statement(s) about metabolism of amino acids

a) alanine aminotransferase (ALT) transforms pyruvate to alanine

b) aspartate aminotransferase (AST) transforms aspartate to a-ketoglutarate

c) glutamine synthetase transforms glutamate to glutamine

d) glutaminase catylyzes conversion of glutamine to ammonia and a-ketoglutarate

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

alanine aminotransferase

(ALT = GPT)

aspartate aminotransferase

(AST = GOT)

Amino transferases important in medicine („transaminases“)

Glutamine is principaltransport form of amino nitrogen

The figure is from http://www.sbuniv.edu/~ggray/CHE3364/b1c25out.html (Dec 2006)

The amino acids can enter the citrate cycle as the molecules

a) alanine → → acetyl-CoA

b) aspartate → oxaloacetate

c) valine → → succinyl-CoA

d) glutamine → → a-ketoglutarate

The amino acids can enter the citrate cycle as the molecules

a) alanine → → acetyl-CoA

b) aspartate → oxaloacetate

c) valine → → succinyl-CoA

d) glutamine → → a-ketoglutarate

The figure is from http://www.biocarta.com/pathfiles/glucogenicPathway.asp (Jan 2007)

The entrance of amino acids into the citrate cycle

Ornithine cycle

a) proceeds only in the liver

b) produces uric acid

c) includes arginine as an intermediate

d) produces energy in a form of ATP

Ornithine cycle

a) proceeds only in the liver

b) produces uric acid

c) includes arginine as an intermediate

d) produces energy in a form of ATP

The figure is from http://www.biocarta.com/pathfiles/ureacyclePathway.asp (Jan 2007)

Detoxication of ammonia in the liver

The figure is from http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch18_TCA-Urea_link.jpg

(Jan 2007)

Interconnection of the urea cycle with the citrate cycle

In the urea synthesis

a) ammonia reacts with ornithine → citrulline

b) carbamoyl phosphate synthetase I (= mitochondrial) regulates the cycle

c) aspartate is used as a –NH2 group donor

d) urea is formed – it can be used as an energy substrate for extrahepatic tissues

In the urea synthesis

a) ammonia reacts with ornithine → citrulline

b) carbamoyl phosphate synthetase I (= mitochondrial) regulates the cycle

c) aspartate is used as a –NH2 group donor

d) urea is formed – it can be used as an energy substrate for extrahepatic tissues

regulatory enzyme activation inhibition

carbamoyl phosphatesynthetase I(= mitochondrial)

N-acetylglutamate

N-acetylglutamatesynthetase

arginine

Regulation of urea cycle

allosteric regulation + enzyme induction by protein rich diet or by metabolic changes during starvation

Urea synthesis is inhibited by acidosis– HCO3

- is saved