amino acid metabolism · nitrogen balance protein catabolism,
DESCRIPTION
Amino acid metabolism · Nitrogen balance protein catabolism, synthesis biosynthesis normal N balance: N ingested = N excreted negative N balance: N ingested < N excreted positive N balance: N ingested > N excreted. (NH 4 + . urea). - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/1.jpg)
Amino acid metabolism · Nitrogen balance
protein catabolism, synthesis biosynthesis
normal N balance: N ingested = N excreted
negative N balance: N ingested < N excreted
positive N balance: N ingested > N excreted
Dietary protein amino acid pool N excretion (NH4+. urea)
![Page 2: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/2.jpg)
Requirement for essential amino acids
![Page 3: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/3.jpg)
Amino acid catabolism · accounts for ~ 10% of energy requirement of adults · When: •· excess protein in diet (amino acids are not stored)
•· protein degradation exceeds demand for new protein
•· starvation when carbohydrates are not available
· (protein storing seeds such as beans, peas, etc.) ·
![Page 4: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/4.jpg)
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, -ketoglutarate, fumarate).
In absence of sugars, glucogenic amino acids permit
continued oxidation of fatty acids by maintaining TCA
cycle intermediates.
Also source of carbons for gluconeogenesis in liver
- ile, phe, tyr, trp
· glucogenic and ketogenic: yield both ketogenic and
glucogenic products.
- all others
![Page 5: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/5.jpg)
N catabolism General strategy:
removal of N from amino acid by transamination (generallyfirst or second step of amino acid catabolic pathways) and
collection of N in glutamic acid
deamination of glutamic acid with release of NH4+
-glutamate dehydrogenase
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.
2
1
4
![Page 6: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/6.jpg)
Pyridoxine Pyridoxal Pyridoxamine
Pyridoxal phosphate
Vitamine B6 family
See Horton: page 212 section 7.7 pyridoxal phosphate
to -amino of lysine
![Page 7: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/7.jpg)
NH
Lys-protein
R1
C-NH3+
COO-
H- +
Schiff base with enzyme
NH Lys-protein
R1
H-C-COO-
Schiff base with substrate
aminoacid-1
1. Transamination reaction see text p 537 and fig 17.7.
![Page 8: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/8.jpg)
NH Lys-protein
R1
H-C-COO-
Schiff base with substrate
NH2Lys-protein
R1
C-
COO-
H- O+
ketoacid-1
Pyradoxamine phosphate
![Page 9: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/9.jpg)
NH Lys-protein
R2
H-C-COO-
NH2Lys-protein
R2
C-
COO-
H- O+ketoacid-2
![Page 10: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/10.jpg)
NH Lys-protein
R2
H-C-COO-
NH
Lys-protein
R2
C-NH3+
COO-
H- +
amino acid-2
![Page 11: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/11.jpg)
Net reaction:
amino acid-1 + ketoacid-2
PLP
amino acid-2 + ketoacid-1
e.g. alanine + -ketoglutarate pyruvate + glutamate
![Page 12: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/12.jpg)
N catabolism General strategy:
removal of N from amino acid by transamination (generallyfirst or second step of amino acid catabolic pathways) and
collection of N in glutamic acid
deamination of glutamic acid with release of NH4+
-glutamate dehydrogenase
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.
2
1
4
![Page 13: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/13.jpg)
2. 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+
![Page 14: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/14.jpg)
3. transport of N to the liver- glutamine synthetase- glutaminase- alanine/glucose cycle
1. Glutamine synthetase
glutamate + NH4+ glutamine
ADP + PiATP
2. Glutaminaseglutamine glutamate + NH4
+
Note: glutamate can be used for glucose synthesis. How?
3. Formation of alanine by transamination: alanine/glucose cycle
![Page 15: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/15.jpg)
Alanine-glucose cycle
Muscle
Liver
glucose
2 pyruvate
2 alanine
2 -aa2 -ka
glucose 2 alanine
glucose
2 pyruvate
2 alanine2 -kG2 Glu
2 NH4+
![Page 16: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/16.jpg)
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
protein
energy
Urea
CO2
![Page 17: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/17.jpg)
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
![Page 18: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/18.jpg)
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
![Page 19: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/19.jpg)
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
+
arginosuccinate
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
![Page 20: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/20.jpg)
5. Arginase (cyto)
HNCH2
CH2CH2
CH
NH3+
COO-
C NH2
H2NNH2CH2
CH2CH2
CH
NH3+
COO-
NH2
C
NH2
O+
ornithine
urea
![Page 21: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/21.jpg)
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
![Page 22: Amino acid metabolism · Nitrogen balance protein catabolism,](https://reader035.vdocuments.net/reader035/viewer/2022070400/56813509550346895d9c5aec/html5/thumbnails/22.jpg)
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