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Metabolisme

Asam Amino
Learning Objective

How proteins are digested in human

How amino acids are degraded in human

How urea is made and excreted


Overview : Oxidation of Amino Acids is a
Significant Energy-Yielding Pathway

Not all organisms use amino acids as the source of


energy
About 90% of energy needs of carnivores can be met by
amino acids immediately after a meal
Only a small fraction of energy needs of herbivores are
met by amino acids
Microorganisms scavenge amino acids from their
environment for fuel
Metabolic Circumstances of Amino Acid Oxidation

Amino acids undergo oxidative


catabolism under three circumstances:

Protein amino-acid residues from Proteins in the body are broken down
normal turnover are recycled to Dietary amino acids that exceed body’s to supply amino acids for catabolism
generate energy and molecular protein synthesis needs are degraded when carbohydrates are in short supply
components (starvation, diabetes mellitus),
Dietary Proteins are Enzymatically Hydrolyzed

Pepsin cuts protein into peptides in the stomach

Trypsin and chymotrypsin cut proteins and larger


peptides into smaller peptides in the small intestine

Aminopeptidase and carboxypeptidases A and B


degrade peptides into amino acids in the small
intestine
Enzymatic
Degradation
of Dietary
Proteins

• (a) gastrin -> secretion of HCl by


parietal cells and pepsin by chief
cells
• (b) exocrine cells synthesize
zymogens
– zymogen granules fuse with plasma
membrane
– zymogens released into the lumen of
the collecting duct
– collecting ducts -> pancreatic duct ->
small intestine.
• (c) Amino acids -> villi ->
capillaries
Protein Metabolism
Protein Metabolism
Nitrogen Pool
Overview
of Amino
Acid
Catabolism
Transamination
Enzymatic Transamination
• Typically, -ketoglutarate accepts
amino groups
• L-Glutamine acts as a temporary
storage of nitrogen
• L-Glutamine can donate the
amino group when needed for
amino acid biosynthesis
• All aminotransferases rely on the
pyridoxal phosphate cofactor
Transamination
Transamination
Oxidative Deamination
Oxidative Deamination
The Amino
Group is
Removed From
All Amino
Acids First
Fates of Nitrogen in Organisms

• Plants conserve almost all the nitrogen


• Many aquatic vertebrates release ammonia to their environment
– Passive diffusion from epithelial cells
– Active transport via gills
• Many terrestrial vertebrates and sharks excrete nitrogen in the form
of urea
– Urea is far less toxic that ammonia
– Urea has very high solubility
• Some animals, such as birds and reptiles excrete nitrogen as uric acid
– Uric acid is rather insoluble
– Excretion as paste allows to conserve water
• Humans and great apes excrete both urea (from amino acids) and uric
acid (from purines)
Excretory
Forms of
Nitrogen
Ammonia in
Transported in the
Bloodstream Safely as
Glutamate

• Un-needed glutamine is
processed in intestines,
kidneys and liver
Glutamate can Donate Ammonia
to Pyruvate to Make Alanine

• Vigorously working muscles


operate nearly anaerobically and
rely on glycolysis for energy
• Glycolysis yields pyruvate that
muscles cannot metabolize
aerobically; if not eliminated lactic
acid will build up
• This pyruvate can be converted to
alanine for transport into liver
Excess Glutamate is Metabolized in the
Mitochondria of Hepatocytes
The Glutamate
Dehydrogenase Reaction

• Two-electron oxidation of
glutamate followed by
hydrolysis
• Net process is oxidative
deamination of glutamate
• Occurs in mitochondrial
matrix in mammals
• Can use either NAD+ or
NADP+ as electron acceptor
Ammonia is Re-captured via Synthesis of
Carbamoyl Phosphate

• This is the first nitrogen-acquiring reaction


Nitrogen from
Carbamoyl
Phosphate
Enters the
Urea Cycle
The Reactions in the Urea Cycle
• 1 ornithine + carbamoyl phosphate => citrulline
– (entry of the first amino group).
– citrulline passes into the cytosol.
• 2a citrulline + ATP => citrullyl-AMP + PPi
• 2b citrullyl-AMP + Aspartate => argininosuccinate + AMP
– (entry of the second amino group).
• 3 argininosuccinate => arginine + fumarate
– fumarate enters the citric acid cycle.
• 4 arginine => urea + ornithine
– Ornithine passes to the mitochondria to continue the cycle
Urea Cycle
N-2 from
Aspartate
Entry of Aspartate into the Urea Cycle

• This is the second nitrogen-acquiring reaction


Aspartate –Arginosuccinate Shunt Links Urea Cycle and
Citric Acid Cycle
Not All Amino Acids can be Synthesized
in Humans

• These amino acids must


be obtained as dietary
protein
• Consumption of a
variety of foods
(including vegetarian
only diets) well supplies
all the essential amino
acids
Fate of Individual Amino Acids
• Seven to acetyl-CoA
– Leu, Ile, Thr, Lys, Phe, Tyr, Trp
• Six to pyruvate
– Ala, Cys, Gly, Ser, Thr, Trp
• Five to -ketoglutarate
– Arg, Glu, Gln, His, Pro
• Four to succinyl-CoA
– Ile, Met, Thr, Val
• Two to fumarate
– Phe, Tyr
• Two to oxaloacetate
– Asp, Asn
Summary of
Amino Acid
Catabolism
Biotin – single C transfers as CO2

• Eg. Pyruvate
Carboxylase
Tetrahydrofolate
• Single Carbon Transfers – intermediate oxidation
state – methylene, formyl, …
S-Adenosyl Methionine
• Methyl Transfers
6 Aminon Acids -> Pyruvate

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


A third Mechanism for Glycine
Degradation
• D-Amino Acids prominent in bacterial
peptidoglycan
• Calcium Oxalate – 75% of Kidney Stones
7 AAs -> Acetyl CoA [W,K,F,Y, L]
7 AAs -> Acetyl CoA [ I , L];
T not shown
W, indole
Ring
Recycling
Metabolic Diseases – Defects of Aromatic
AA degradation
R, H, P, E,Q -> α-
ketoglutarate
I, M, T, V->
Succinyl-CoA
Branched-chain amino acids: valine, isoleucine,
and leucine.
Asp and Asn to
oxaloacetate.
Summary of
Amino Acid
Catabolism
Summary
In this chapter, we learned that:

• Amino acids from protein are an important energy source in


carnivorous animals
• Catabolism of amino acids involves transfer of the amino group via PLP-
dependent aminotransferase to a donor such as -ketoglutarate to
yield L-glutamine
• L-glutamine can be used to synthesize new amino acids, or it can
dispose of excess nitrogen as ammonia
• In most mammals, toxic ammonia is quickly recaptured into carbamoyl
phosphate and passed into the urea cycle