Amino oke akhirnua

selesai Acid Metabolism

Chem 4220
IAUPR Barranquitas
JA Negrón
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 Summary
• Introduction to protein metabolism
• Ubiquitin and protein degradation
• Amino acid pool
• Transamination
• Urea cycle
• Ketogenic and glucogenic amino acids

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JA Negrón, Ph.D.
 Introduction to Protein Metabolism
• Anabolism
– Biosynthesis of Proteins
• Catabolism
– Urea cycle
– Amino acid catabolic pathways
– The destruction of proteins is as important as their
synthesis for the maintenance of protein homeostasis
in cells.
– In eukaryotes, the ubiquitin–proteasome system
(Nobel Prize in Chemistry 2004) is responsible for
most of this protein degradation.

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JA Negrón, Ph.D.
 Ubiquitin–proteasome system
• It is known that ubiquitin-mediated
destruction plays a crucial part in cell-cycle
regulation, DNA repair, cell growth and
immune function, as well as in hormone-
mediated signalling in plants.
• Ubiquitin has been shown to have numerous
non-proteolytic functions.

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JA Negrón, Ph.D.
 UBIQUITIN
● 76 Amino Acid polypeptide
● Highly conserved in evolution: 3 Amino
acid differences between yeast and human
homologues

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JA Negrón, Ph.D.
 The Ubiquitin Pathway
Ub
Ub Ub

E1 E2 E3

Target
Ub
Ub
Ub
Ub

26s proteosome degradation

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JA Negrón, Ph.D.
Ubiquitin Pathway

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JA Negrón, Ph.D.
ATP consuming process

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 Nitrogen
• Natural occurring nitrogen, N2, is not usable in
biological systems.

• Only a few organisms can convert N2 to NH3,

which is usable by biological systems.

• Most organisms guard NH3 very closely, however,

because of the routine intake of NH3 containing
compounds we need a way to rid of it.
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JA Negrón, Ph.D.
 N2 balance

2 2

• Protein-major dietary source of N2

• Amino acids
– Protein synthesis
– N2 containing compounds
– Excess disposed through urea (80%), ammonia, uric
acid, creatinine in urine (very small amount in fecal
matter) 10
JA Negrón, Ph.D.
 Amino Acid Pool
Dietary Proteins
↓ Digestion
Plasma Anabolism
Amino Acid Tissue Proteins
Proteins pool Catabolism

Deamination

Amino
acid α –ketoacid residues (from Excretion
derivatives carbon skeletons of amino acids
↓ Urea, ammonia in the
Energy metabolism in pathways urine
of glucose or fatty acid
metabolism
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JA Negrón, Ph.D.
Amino Acid Pool, more details

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JA Negrón, Ph.D.
 Essential and Non-essential AAs
• Essential AAs-Humans (mammals)
cannot synthesize their carbon skeletons
de novo. Some EAA are considered
essential because we cannot synthesize
enough, especially for growth (children).
• Non-essential AAs-Synthesized from
intermediates of glucose/TCA cycle
except TYR (cannot make aromatic ring).
• Conditionally essential
– Arg: Not enough
– His: Essential for growth in children
– Phe: Necessary to produce Tyr
– Tyr: Made from Phe (phenylketonuria)
– Cys: Produce from Met
– Pro: Made from Glu and ornithine (urea)
– Gln: critically ill, stress (fuel for proliferative
tissues)

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JA Negrón, Ph.D.
 Amino Acid Degradation
Amino
Acids

NH3
↓
↓
↓
CO2 + H2O
Urea
Cycle
Acetyl
CoA

Acetoacetyl
CoA 14
JA
 Catabolism of amino acids

• Amino acid catabolism takes place in the liver.

• The first step is the removal of the α-amino

group by enzymes called amino-transferases or
transaminases.

• The amino group is transferred to α-

ketoglutarate to make glutamate.
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JA Negrón, Ph.D.
 Glutamate

• Amino acid catabolism takes

place in the liver.
• The receiver of the amino
group from amino acids in the
liver is α-ketoglutarate and
its product is glutamate.
• The enzyme is an amino-
transferases or
transaminases.
• Pyridoxal phosphate (PLP) or
the active form of Vitamin B-
6 is required by the amino
transferase. 16
JA Negrón, Ph.D.
• Glutamate releases
its amino group as
ammonia in the
mitochondria of liver
cells by glutamate
dehydrogenase
GluDesh
(GluDesh), the only
enzyme that can use
either NAD+ or
NADP+ as reducing
equivalent receivers.

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JA Negrón, Ph.D.
 Major Functions of Amino Acids
Oxidation
Derived
Glycogenic from
amino acids: --BloodDietary Protein
glucose--Energy
Ketogenic amino acids: -Acetyl CoA-Stored fat-Energy
Biosynthesis of nitrogen-containing metabolites
Heme Blood cell
Choline PL
Glycosamine Sugar
Nucleotides DNA
Protein synthesis Protein
Biogenic amines Neurotransmitters
Carnitine Heart
Creatine phosphate « Energy »

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JA Negrón, Ph.D.
The different forms of excreted nitrogen

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 Urea Cycle
• Urea is the major end
product of nitrogen
metabolism in humans and
mammals.
• Ammonia, the product of
oxidative deamination
reactions, is toxic in even small
amounts and must be
removed from the body.
• The urea cycle or the ornithine
cycle describes the conversion
reactions of ammonia into
urea.
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JA Negrón, Ph.D.
 Urea
• If not used in the production of new amino acids
or other nitrogenous compounds, amino groups
are transferred to the liver and converted to urea.

• Urea is produced in the cytosol via the urea cycle.

• Almost all urea is produced in the liver.

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JA Negrón, Ph.D.
 Urea
• Urea produced in liver cells then passes into the
bloodstream.

• It then finds its way to the kidneys to be excreted

in the urine.

• Urea is very soluble in water - about 10.5 M at

25° C.

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JA Negrón, Ph.D.
 The Urea Cycle
• A five step process.

• The first two steps take place within the

mitochondrion.

• The remaining three of which take place in the

cytosol.

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JA Negrón, Ph.D.
The enzymes catalyzing
the urea cycle
reactions
1. ornithine
transcarbamoylase

2. argininosuccinate
synthetase

3. argininosuccinase

4. arginase

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