Faculdade de Desporto, Universidade do Porto, 1º Ciclo, 1º Ano

202_2013

BIOQUÍMICA E BIOLOGIA CELULAR

António Ascensão, José Magalhães

Metabolism of proteins and amino acids

Humans degradation of ingested proteins

Nonessential and essential amino acids

Nonessential – synthesized by body; usually nonessential in diet!Essential – not synthesized by body; essential in diet!

General amino acid structure and peptide linkage …

Lateral chain

Amino acid structure (some examples …)

Glutamate Lysine Histidine Valine

Amino group

Carboxil group

α carbon

Lateral Chain

(R)

Polypeptide and primary protein structure

Body´s amino acid pool

Leave the body

Enter the body

Amino acids undergo oxidative degradation …

1.  … during normal cellular protein “turnover” (synthesis and degradation of proteins), when amino acids that are released from protein breakdown are not needed for new proteins synthesis

2.  … when a diet is rich in proteins and the ingested amino acids exceed the body's needs for protein synthesis (amino acids cannot be stored)

3.  … during starvation, prolonged intense exercise or uncontrolled diabetes when carbohydrates are either unavailable or not properly utilized (amino acids are used as fuel)

Overview of amino acid catabolism in mammals

Amino acid energetic-related catabolism

Removal of amina group from amino acids (transamination)

The effect of transamination is to collect the amino groups from many different amino acids in the form of Glutamate.

Glutamate then functions as an amino donor for biosynthetic pathways

or for excretion pathways eliminating nitrogenous waste products

Transamination and oxidative deamination

Transamination

Oxidative deamination (only in mitochondria)

Transamination and oxidative deamination

Transamination and oxidative deamination

Transamination

Oxidative deamination (only in mitochondria)

α- ketoglutarate

+

α- Ketoglutarate

…

+

α- Keto acids

+

(ready for metabolism ex. krebs cycle)

(ready for metabolism in krebs cycle or glucose synthesis)

(excretion as NH4

+, uric acid or urea)

Common transamination reactions

TGO Transaminase

Glutâmico-Oxaloacética

Transaminase Glutâmico-Pirúvica

TGP

(Amino groups acceptor)

(Amino groups acceptor)

Oxidative Deamination (in mitochondria)

Occurs essentially in liver mitochondrial matrix

Involves NAD+ as the oxidizing agent

Reaction catalyzed by glutamate dehydrogenase

Glutamate dehydrogenase

Biosynthesis Urea cycle

Glutamate, glutamine and alanine (special cases …)

1.  … in the cytosol of hepatocytes amino groups are transferred to α-ketoglutarate to form glutamate which enters mitochondria and gives up its amino group to form ammonium (NH4

+) (used in biosynthesis of other amino acids, nucleotides or excreted);

2.  … excess ammonia (toxic compound that must be converted in a non-toxic before exported to liver trough bloodstream) in most other extrahepatic tissues is converted into glutamine and transported to the liver, then into liver mitochondria;

3.  … in skeletal muscle amino groups are transferred to pyruvate to form alanine which transports them to the liver.

Glutamine-related NH4+ transport from extrahepatic tissues

Extr

ahep

atic

tiss

ues

Live

r

Glutamine- Glucose cycle

Liver kidneys

Extrahepatic Tissues

Glutamate

Amino Acids (NH4

+)

Glutamine

Alanine - glucose cycle (skeletal muscle - liver)

(TGP)

(TGP)

Overview of amino acids metabolization in the liver …

TGP

Glutamato dehydrogenase

Transaminases (aminotransferases)

Glu

tam

inas

e

Urea cycle and reactions that feed amino groups into cycle

(TGO)

Metabolic fate of amonium (NH4+) in liver mitochondria …

Oxidative Deamination

Liver urea (2 amino groups) is produced in 5 steps …

Bloodstream until kidneys and excreted in urine" Into"

Krebs cycle"

1"

5" 4"

3"2"

First amino group" Second"amino group"

Two amino groups"

From mitochondria TGO reaction"

(see next slide)"

Links between the urea and krebs cycles (Krebs bicycle !)

Oxaloacetate (TGO)

Oxidative Deamination

Red

uces

the

ener

getic

cos

t of u

rea

synt

hesi

s (r

egen

erat

ion

of o

xalo

acet

ate

via

aspa

rtat

e)

(↓ 2 ATP)

(↓ 1 ATP)

(↑ 2.5 ATP)

Summary of amino acid catabolism