Amino acid metabolism · Nitrogen balance protein catabolism,
description
Transcript of Amino acid metabolism · Nitrogen balance protein catabolism,
Amino acid metabolism · Nitrogen balance
protein catabolism, synthesis biosynthesis
normal N balance: N ingested = N excretednegative N balance: N ingested < N excretedpositive N balance: N ingested > N excreted
Dietary protein amino acid pool N excretion(NH4
+. urea)
Amino acid catabolism · accounts for ~ 10% of energy requirement of adults · When: · excess protein in diet· protein degradation exceeds demand for new protein· starvation when carbohydrates are not available· protein storing seeds such as beans, peas, etc. · Glucogenic vs ketogenic amino acids
· ketogenic: yield AcCoA or AcAc as end products of catabolism - leu, lys
· glucogenic: are degraded to pyruvate or a member of the TCA cycle (succinylCoA, OAA, a-ketoglutarate, fumarate). In absence of sugars, glucogenic amino acids permit continued oxidation of fatty acids by maintaining TCA cycle intermediates. - ile, phe, tyr, trp
· glucogenic and ketogenic: yield both ketogenic and glucogenic products. - all others
N catabolism General strategy:
1. removal of N from amino acid by transamination (generally first or second step of amino acid catabolic pathways) and collection of N in glutamic acid
deamination of glutamic acid with release of NH4+
-glutamate dehydrogenase2.
3. Collection of N in glutamine or alanine for delivery to liver
removal of NH4+ by : i. secretion; or ii. conversion to
urea or other less toxic form.4.
Pyridoxine Pyridoxal Pyridoxamine
Pyridoxal phosphate
Vitamine B6 family
See Horton: page 212 section 7.7 pyridoxal phosphate
to -amino of lysine
NH Lys-protein
NH
Lys-protein
R1
C-NH3+
COO-
H- +
R1
H-C-COO-
Schiff base with enzyme
Schiff base with substrate
aminoacid-1
Transamination reaction see text p 537 and fig 17.7.
NH Lys-protein
R1
H-C-COO-
Schiff base with substrate
NH2Lys-protein
R1
C-
COO-
H- O+
ketoacid-1
NH Lys-protein
R2
H-C-COO-
Schiff base with substrate
NH2Lys-protein
R2
C-
COO-
H- O+
-keto acid
ketoacid-2
NH Lys-protein
NH
Lys-protein
R2
C-NH3+
COO-
H- +
R2
H-C-COO-
Schiff base with enzyme
Schiff base with substrate
amino acid-2
Net reaction:
amino acid-1 + ketoacid-2
PLP
amino acid-2 + ketoacid-1
e.g. alanine + -ketoglutarate pyruvate + glutamate
Alanine-glucose cycle
Muscle
Liver
glucose
2 pyruvate
2 alanine
2 -aa
2 -ka
glucose 2 alanine
glucose
2 pyruvate
2 alanine2 -kG
2 Glu
2 NH4+
glutamate dehydrogenase (see p 533 for reaction)
• - release or capture of NH4+
· - located in mitochondria
· - operates near equilibrium
glutamate + H2O -ketoglutarate + NH4+
NAD NADH
NADPHNADP
amino acid + -ketoglutar keto acid + glutamate
glutamate + NAD + H2O -ketoglutar +NADH + H+ + NH4+
amino acid + NAD + H2O -keto acid +NADH + H+ + NH4+
3. transport of N to the liver- glutamine synthetase- glutaminase- alanine/glucose cycle
1. Glutamine synthetase
2. Glutaminase
glutamate + NH4+ glutamine
ADP + PiATP
glutamine glutamate + NH4+
Note: glutamate can be used for glucose synthesis. How?
Glu
KGaa
ka Pyr
Ala
Glu’NH2NH4
+
KG Glu
Ala Pyr
NH4+
Glu’NH2
Glucose
Glucose
LIVER
2Glu’NH22GluKG
Glucose
2NH4+ 2NH4
+
4CO2
CO2HCO3 + H+H2CO3
H2O
KIDNEY
MUSCLE
Urea
Urea cycle
Where: Liver: mito/cyto
Why: disposal of N
Immediate source of N: glutamate dehydrogenaseglutaminase
Fate of urea:liver kidney urine
How much: ~ 30g urea / day
Reactions of urea cycle
1. Carbamyl phosphate synthetase I (mito)
NH4+ + HCO3
- + 2 ATP H2N-C-OPO3-2 + Pi + 2 ADP
O
carbamyl phosphate
• committed step
• by N’Ac glutamate
2. Ornithine transcarbamylase (mito)
NH2CH2
CH2CH2
CH
NH3+
COO-
HNCH2
CH2CH2
CH
NH3+
COO-
CNH2
ONH2
COPO3
-2O+
Pi
ornithinecitrulline
carbamylphosphate
3. Arginosuccinate synthetase (cyto)
HNCH2
CH2CH2
CH
NH3+
COO-
CNH2
OCOO-
CH2CH
COO-
NH3+
HNCH2
CH2CH2
CH
NH3+
COO-
C NH
COO-
CHCH2
COO-
H2N
ATP AMP+
PPi
+
4. Arginosuccinate lyase (cyto)
HNCH2
CH2CH2
CH
NH3+
COO-
C NH
COO-
CHCH2
COO-
H2N
HNCH2
CH2CH2
CH
NH3+
COO-
C NH2 COO-
CHCH
COO-
H2N
+
arginine
fumarate
arginosuccinate
5. Arginase (cyto)
HNCH2
CH2CH2
CH
NH3+
COO-
C NH2
H2NNH2CH2
CH2CH2
CH
NH3+
COO-
NH2
C
NH2
O+
ornithine
urea
NH2CH2
CH2CH2
CH
NH3+
COO-
+
NH2
COPO3
-2O
HNCH2
CH2CH2
CH
NH3+
COO-
CNH2
O
HNCH2
CH2CH2
CH
NH3+
COO-
C NH
COO-
CHCH2
COO-
H2N
HNCH2
CH2CH2
CH
NH3+
COO-
C NH2
H2N
NH2
C
NH2
O
ornithine
ornithine
fumarate
asparate
glutamate
KG
citrulline
asparate
glutamate
NAD
NADH + H+
HCO3
2ATP2ADP +Pi
ATP
AMP + PPi
MITO
CYTO
See fig 17.26
Glu’NH2Glu’NH2
cittruline
cittruline
Arginine
creatine
ArginineArg
Ornithine
Ureacycle
Glu’NH2
creatine
P-creatine
creatinine Severalsteps
Severalsteps
Severalsteps
Urea
To urine
Epithelial cells of intestine
Kidney
Muscle
Liver
glutamate
2steps
Adapted from Devlin, Biochemistry with Clinical Corrleation4th ed.
Interorgan relationships in N metabolism