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Amino Acids

Metabolism
1. Amino Acids Biosynthesis
2. Amino Acids Breakdown
-Deamination
-Urea Cycle
DR. AIRIANAH
airianah@ukm.edu.my

Amino Acids Biosynthesis

Essential and nonessential amino


acids in human

*
Essential
in
juveniles

Essential

Nonessential

Arginine*

Alanine

Histidine*

Asparagine

Isoleucine

Aspartate

Leucine

Cycteine

Lysine

Glutamate

Methionine

Glutamnine

Phenylalanine

Glycine

Threonine

Proline

Tryptophan

Serine

valine

Tyrosine

Reff-slide: Dr. Nik Marzuki

Amino Acids Biosynthesis

Biosynthetic Families
Metabolic Precursors
Pyruvate/
Pyruvate Family

Amino Acids
Alanine
Valine
Leucine
Isoleucine

Oxaloacetate/
Aspartate Family

Aspartate
Asparagine
Methionine
Threonine
Lysine

Amino Acids Biosynthesis

Metabolic Precursors
-ketoglutarate/
Glutamate Family

Amino Acids
Glutamate
Glutamine
Proline
Arginine

3-Phophoglycerate/
Serine Family

Serine
Glycine
Cysteine

Amino Acids Biosynthesis

Metabolic Precursors
Phosphoenolpyruvate/
erythrose 4-P (Chorismate)

Amino Acids
Tryptophan
Phenlyalanine
Tyrosine

Ribose 5-phosphate/PRPP

Histidine

Amino Acids Biosynthesis-nonessential

Amino Acids Biosynthesis-essential

Amino Acids Biosynthesis

Rib-5-P

Gluc-6-P

Ery-4-P

PRPP
ATP

F-6-P

HIS
F-1,6-P2

LYS

Shikimate

LEU

SER

3-PGA
DA-Pim

VAL

CYS

-KIV

Chorismate

Prephenate

GLY

PHE

TYR

PEP

DH-Pic

ALA

TRP
Pyruvate

ASN
-AspCHO

AcetylCoA

ASP

Homoserin

OAA

Citrate

Malate

Isocitr

MET

THR

ILE

Fumarate

Succinate

-KG

SuccCoA

PRO
GLU

GLN
Ornithin

ARG

Aspartate family

Serine family

Glutamate family

Pyruvate family

PRPP/Histidine

Aromatic family

AMINO ACID BREAKDOWN


proteins are continually synthesised and degraded
proteins have half-lives that range from minutes to weeks
rate of protein degradation also influence by metabolic requirement
excess amino acid neither stored nor excreted
levels of amino acids are tightly regulated
Amino acids (20) are degraded to compounds that can be metabolised to CO2 and
H2O OR gluconeogenesis
degradation of AAs produce only NH4+ and carbon skeletons
10% of the metabolic energy comes from carbon skeletons of AA
20 AA are degraded to JUST 7 metabolite: acetyl-CoA, succinyl-CoA, pyruvate, ketoglutarate, fumarate, oxaloacetate, acetoacetate
intermediates Succinyl-CoA, pyruvate, -KG, fumarate and OAA can serve as

precursor for glucose synthesis (gluconeogenesis). Therefore, AA giving rise


to these intermediate are called glucogenic
AA degraded to acetyl-CoA and acetoacetate are ketogenic

Amino Acids Breakdown

Amino Acids Deamination

Amino Acids Deamination

Amino Acids Deamination

Urea Cycle

N excretion occurs by 3 different products


i. NH3 aquatic animals (ammonotelic)
ii. Urea most terrestrial vertebrates (ureotelic)
iii. Uric acid birds and reptiles (uricotelic)
N from muscle is transported to liver as alanine
N from other tissues are transported to liver as their respective amino acids

Urea Cycle

1- ornithine
transcarbamoylase
2- orgininosuccinate
synthetase
3- argininosuccinase
4- arginase

Urea Cycle

The fate of fumarate? (Converted to malat OAA)


i. Intermediate for TCA cycle
ii. Gluconeogenesis
iii. Re-converted to argininosuccinate (intermediate
for urea cycle)

Reff-slide: Dr. Nik Marzuki

Urea Cycle

Krebs Bicycle

Krebs Bicycle

Reff-slide: Dr. Nik Marzuki

Regulation of urea cycle


the reaction that catalysed by CPS1 is the rate
limiting step
CPS1 is allosterically activate by N-acetylglutamate
Glu + Acetyl-CoA

N-acetylglutamate
synthase

N-acetylglutamate

high rate of AA degradation results in increasing


level of glu
glu, N-acetylglutamate, CP, urea cycle, excess
N excreted
other enzymes are controlled by their substrate

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Overview of amino acid catabolism

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