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Protein Metabolism

From: Protein Data Bank PDB ID: 1B0E 1


Kalus, W., Zweckstetter, M., Renner, C., Sanchez, Y., Georgescu, J., Grol, M., Demuth, D., Schumacher, R., Dony, C., Lang, K., Holak, T. A.: structure of the IGF-binding
domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions. EMBO J 17 pp. 6558 (1998)
Nitrogen balance

Protein content of adult body


remains remarkably constant
Protein constitutes 10-15% of diet
Equivalent amount of amino acids must
be lost each day

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Protein Catabolism
Breakdown of protein into amino acids
Liver cells convert amino acids into
substances that can enter the Krebs cycle
deamination removes the amino group
(NH2)
converts it to ammonia (NH3) & then
urea
urea excreted in the urine

Converted substances enter the Krebs cycle


to produce ATP
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Protein Catabolism

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Protein Anabolism
Production of new proteins by
formation of peptide bonds
between amino acids
10 essential amino acids are
ones we must eat because we
can not synthesize them
nonessential amino acids can be
synthesized by transamination
(transfer of an amino group to a
substance to create an amino
acid)
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Protein Anabolism
Occurs on ribosomes in almost every
cell
Stimulated by insulinlike growth
factor, thyroid hormone, insulin,
estrogen & testosterone
Large amounts of protein in the diet
do not cause the growth of muscle,
only weight-bearing exercise

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Amino acid pool
No storage facility for amino acids
Amino acids incorporated into functional
proteins
Amino acids in blood and extracellular
fluid represent an amino acid pool
Amino acids move through this pool
Average 60 kg woman
10 kg protein
170 g free amino acids in pool
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Fate of amino acids
If not required for protein synthesis amino
groups removed
For most amino acids occurs primarily in liver
For certain amino acids (leucine, isoleucine, valine)
occurs primarily in skeletal muscle)
amino groups transferred to form alanine and taken to
liver for disposal via glucose-alanine cycle
Carbon skeletons used for:
Gluconeogenesis (in liver)
Oxidised in Krebs Cycle
Amino groups used for:
Synthesis of nonprotein nitrogen compounds
Disposed of via Urea Cycle
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GLUCOSE-ALANINE CYCLE

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FATE OF AMINO ACIDS

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Amino acid metabolism

Metabolism of amino acids differs,

but 3 common reactions:

Transamination

Deamination

Formation of urea

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Transamination reactions
Amino group removed from one amino acid and
transferred to another
Catalysed by aminotransferase enzymes

Nearly all transaminations transfer amino group to


-ketoglutarate
Forms new ketoacid and glutamate (amino acid)

Amino acids transaminations in skeletal muscle


usually result in formation of alanine (via
glutamate)
Released from muscle

Allows amino groups from amino acids to move


from skeletal muscle to liver for disposal

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Deamination reactions
Amino group (and H) removed
Forms ammonia (NH3)
Carbon skeleton left can be
oxidised in Krebs Cycle
used for gluconeogenesis

converted to fatty acid

18 amino acids glucogenic/ketogenic


Leucine and lysine purely ketogenic

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Amino Acid Biosynthesis
Plants and microorganisms can make all 20
amino acids and all other organisms need N
metabolites
In these organisms, glutamate is the source
of N, via transamination (aminotransferase)
reactions
Mammals can make only 10 of the 20 amino
acids
The others are classed as "essential" amino
acids and must be obtained in the diet
All amino acids are grouped into families
according to the intermediates that they are
made from
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The -Ketoglutarate Family

Glu, Gln, Pro, Arg, and sometimes


Lys

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The glutamate synthase reaction

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Glutamate-dependent transamination - primary mechanism for
amino acid synthesis

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Proline biosynthesis from glutamate

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Synthesis of ornithine from glutamate - a step in
arginine biosynthesis

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The Aspartate Family
Asp, Asn, Lys, Met, Thr, Ile

Transamination of oxaloacetate gives


Asp
Amidation of Asp gives Asn
Thr, Met, and Lys are made from Asp

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Asp + Gln --> Asn + Glu

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Transamination of oxaloacetate yields
aspartate

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The Pyruvate Family
Ala, Val, Leu

Transamination of pyruvate gives Ala


Val is derived from pyruvate
Leu synthesis, like that of Ile and Val,
begins with an -keto acid
Transaminations from Glu complete each
of these pathways

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ALANINE BIOSYNTHESIS

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3-Phosphoglycerate Family
Ser, Gly, Cys
3-Phosphoglycerate dehydrogenase
diverts 3-PG from glycolysis to amino
acid paths
Transamination by Glu gives 3-P- serine
Phosphatase yields serine
A piridoxal phosphate-dependent
enzyme makes Cys

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Biosynthesis of
serine from 3-
phosphoglycerate

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Glycine biosynthesis from serine

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Cysteine biosynthesis

Sulfhydration of serine by sulfide

Sulfhydration of O-acetylserine

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The Phosphoenolpyruvate Family

Phe, Tyr, Trp

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BIOSYNTHESIS TYROSINE

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Degradation of Amino Acids

The 20 amino acids are


degraded to produce TCA and
glycolytic intermediates

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Degradation of
amino acids

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Degradation of Ala,
Ser, Cys, Gly and Trp
and Thr to pyruvate

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Urea cycle
Ammonia is toxic
Readily ionises to ammonium ion NH4+
NH4+ converted to urea in liver (urea
cycle)
Urea contains 2 x NH2
One from NH4+
One from aspartate
Urea excreted in urine
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UREA CYCLE

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Urea Cycle

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