SlideShare une entreprise Scribd logo
1  sur  15
AMINO ACID
METABOLISM
(part 1)
OVERVIEW OF CENTRAL AMINO ACID METABOLISM
ENVIRONMENT ORGANISM
Ingested
Diatary
proteins
70-100g/d
Bio-
synthesis Body
Proteins
35-200g/d
AMINO
ACIDS
Nitrogen
(NH3)
Carbon
skeletons
(Keto- acids)
Urea
Degradation
(required)
1 2 3
a
b
Purines
Pyrimidines
Porphyrins (heme)
Niacin
Neurotansmitters
Polyamines
c c
Used for energy
pyruvate
α-ketoglutarate
succinyl-CoA
fumarate
oxaloacetate
acetoacetate
acetyl CoA
(glucogenic)
(ketogenic)
CO2
+
Water
Metabolic Classification of the Amino Acids
• Based on synthesis:
Essential and Non-essential
• Based on degradation (Fate):
Glucogenic and Ketogenic
Essential Amino Acids in Humans
• Required in diet
• Human is incapable of forming their requisite carbon skeleton
Non-essential Amino Acids in Humans
• Not required in diet
• Can be formed from α-keto acids by transamination and subsequent
reactions
• Valine
• Leucine
• Isoleucine
• Methionine
• Phenylalanine
•Tryptophan
• Threonine
•Histidine*
• Lysine
•Glycine
•Alanine
•Proline
•Tyrosine* •Serine
•Cysteine*
•Glutamine
•Asparagine
•Glutamate
•Aspartate
•Arginine*
DEGRADATION (FATE) OF THE CARBON SKELETONS
Carbon skeletons are used for energy.
Glucogenic Amino Acids: degradead to TCA cycle intermediates Oxaloacetate,
Fumarate,Succinyl CoA, α-ketoglutarate,
or pyruvate (gluconeogensis).
Ketogenic Amino Acids: degraded to acetyl CoA, acetoacetyl CoA, or
acetoacetate ( form ketone bodies).
AMINO ACID DEGRADATION INTERMEDIATESAMINO ACID DEGRADATION INTERMEDIATES
CO2
CO2
Pyruvate
Acetyl-CoA Acetoacetate
Citrate
Isocitrate
-ketoglutarate
Succinyl-CoA
Fumarate
Oxaloacetate
Citric
Acid
Cycle
CO2
Glucose
Ala Ser
Cys Thr*
Gly Trp*
Ile*
Leu•
Lys•
Thr*
Leu• Trp*
Lys• Tyr*
Phe*
Asn
Asp
Asp
Phe*
Tyr*
Ile*
Met
Val
Arg His
Glu Pro
Gln
Glucogenic
Ketogenic
* Both Glucogenic and Ketogenic
• Purely Ketogenic
PEP
Malate
Succinate
Incorporation of NH4
+
Into
Organic Compounds
1) NH4
+
+ HCO3
-
+ 2 ATP NH2CO2PO3
-2
+ 2 ADP +
Carbamoyl Phosphate Pi + 2 H+
2) NH4
+
+
Carbamoyl
Phosphate
Synthetase I
(CPS-I)
Glutamate
dehydrogenase
O
-
O2CCH2CH2CCO 2
-
-Ketoglutarate
Glutamate
NADP +NADPH +
H+
NH3
+
-
O2CCH2CH2CHCO 2
-
TCA Cycle
Incorporation of NH4
+
Into
Organic Compounds (Cont.)
NH3
+
-
O2CCH2CH2CHCO 2
- + NH4
+
+ 2 ATP
NH3
+O
H2NCCH2CH2CHCO 2
-
Glutamine
Glutamate Glutamine
Synthetase
Mg++
N of glutamine donated to other compounds
in synthesis of purines, pyrimidines,
and other amino acids
3)
Biosynthesis of Amino Acids
*Transaminations:
Amino Acid1 +α-Keto Acid2  Amino Acid2 +α-Keto Acid1
+
O
R-CCO 2
-
Glutamate
Pyridoxal phosphate (PLP)-
Dependent Aminotransferase
+
α- Ketoglutarate
Biosynthesis of Essential Amino Acids
Their -ketoacids are not common intermediates (enzymes needed to form them
are lacking) so transamination is not an option.
Biosynthesis of Non-essential Amino Acids
Transamination of -ketoacids that are available as common intermediates.
(treatment of hyperamonemia)
All (except Tyr) synthesized from the common intermediates synthesized in cell :
• Pyruvate
• Oxaloacetate
• -ketoglutarate
• 3-phosphoglycerate
NH3
+
-
O2CCH2CH2CHCO 2
-
NH2
R-CHCO 2
-
O
-
O2CCH2CH2CCO 2
-
Transamination Reactions : One Step
Pyruvate + AA  Alanine + -ketoacid
Oxaloacetate + AA Aspartate + -ketoacid
-ketoglutarate + AA Glutamate + -ketoacid
Transaminases: Equilibrate amino groups among -ketos. Require pyridoxal
phosphte (PLP).
Blood transaminases has a diagnostic value. (AST or GOT , ALT or GPT)
All AAs, except Lys and Thr, can be transaminated. Most transaminases
generate Glu or Asp.
*ATP-dependent amidation of Glu, Asp:
 GLU + ATP + NH3  GLN + ADP + Pi
By the nnzyme glutamine synthetase Where NH3 is toxic ; stored
as Gln.
Gln donates amino gps in many reactions
 ASP + ATP + GLN  ASN + AMP + PPi + GLU
By the enzyme Asparagine synthetase.
Low in some cell tumor types. ( Asparaginase treatment ) .
Transaminations
Glutamate -Ketoglutarate
+ +
Pyruvate Alanine
Glutamate -Ketoglutarate
+ +
Oxaloacetate Aspartate
Glutamate-Pyruvate
Aminotransferase
(Alanine Transferase ALT)
Glutamate-Oxaloacetate
Aminotransferase
(Aspartate Transferase AST)
Blood levels of these aminotransferases, also called transaminases,
are important indicators of liver disease
AAMMIINNOO AACCIIDD CCAATTAABBOOLLIISSMM
AA.. NNiittrrooggeenn ((NNHH3))
H2N C
O
NH2
urea
Most terrestrial land animals convert excess nitrogen to urea, prior to excreting it.
Urea is less toxic than ammonia.
The Urea Cycle occurs mainly in liver excreted by kidney.
The 2 nitrogen atoms of urea enter the Urea Cycle as NH3 (produced mainly via
Glutamate Dehydrogenase) and as the amino N of aspartate.
The NH3 and HCO3 (carbonyl C) that will be part of urea are incorporated first
into carbamoyl phosphate.
Carbamoyl Phosphate Synthetase
is the committed step of the Urea
Cycle, and is subject to regulation.
H2N C OPO3
2
O
HCO3

+ NH3 + 2 ATP
+ 2 ADP + Pi
Carbamoyl Phosphate
Synthetase
carbamoyl phosphate
N
H
C COO
CH2
CH2
COO
H
CH3C
O
N-acetylglutamate
H3N+
C COO
CH2
CH2
COO
H
glutamate (Glu)
Carbamoyl Phosphate Synthetase has
an absolute requirement for an allosteric
activator N-acetylglutamate.
This derivative of glutamate is
synthesized from acetyl-CoA &
glutamate when cellular [glutamate] is
high, signaling an excess of free amino
acids due to protein breakdown or
dietary intake.
H2N C OPO3
2
O
CH2
CH2
CH2
HC
COO
NH3
+
NH3
+
CH2
CH2
CH2
HC
COO
NH3
+
NH
CO NH2
COO
CH2
HC
COO
NH2
CH2
CH2
CH2
HC
COO
NH3
+
NH
C NH2
+
COO
CH2
HC
COO
H
N
AMP + PPi
ATP
CH2
CH2
CH2
HC
COO
NH3
+
NH
C
NH2
+
H2N
COO
HC
CH
COO

C NH2H2N
O H2O
Pi
ornithine
urea
citrulline
aspartate
arginino-
succinate
fumarate
arginine
carbamoyl
phosphate
Urea Cycle
1
2
3
4
Urea Cycle
-Enzymes in
mitochondria:
1. Ornithine
Trans-
carbamylase
-Enzymes in
cytosol:
2. Arginino-
Succinate
Synthetase
3. Arginino-
succinase
4. Arginase.
Fumarate is converted to oxaloacetate via Krebs Cycle.
Oxaloacetate is converted to aspartate via transamination
(e.g., from glutamate).
Aspartate then reenters Urea Cycle, carrying an amino group
derived from another amino acid.
aspartate -ketoglutarate oxaloacetate glutamate
Aminotransferase (Transaminase)
COO
CH2
CH2
C
COO
O
COO
CH2
HC
COO
NH3
+
COO
CH2
CH2
HC
COO
NH3
+
COO
CH2
C
COO
O+ +
Hereditary deficiency of any of the Urea Cycle enzymes leads to
hyperammonemia - elevated [ammonia] in blood.
Total lack of any Urea Cycle enzyme is lethal.
Elevated ammonia is toxic, especially to the brain.
If not treated immediately after birth, severe mental retardation results.
Postulated mechanisms for toxicity of high [ammonia]:
1. High [NH3] would drive Glutamine Synthetase:
glutamate + ATP + NH3  glutamine + ADP + Pi
This would deplete glutamate – a neurotransmitter & precursor for
synthesis of the neurotransmitter GABA (later) .
2. Depletion of glutamate & high ammonia level would drive Glutamate
Dehydrogenase reaction to reverse:
glutamate + NAD(P)+
α-ketoglutarate +
NAD(P)H + NH4
+
The resulting depletion of α-ketoglutarate, an essential Krebs Cycle
intermediate, could impair energy metabolism in the brain.
Deficiencies related to Urea Cycle
Carbamoyl Phosphate Synthetase Deficiency
and N-acetylglutamate synthetase Deficiency
Ornithine Transcarbamoylase Dificiency
Argininosuccinate Synthetase and Lyase Deficiencies
Arginase Deficiency
• Blood Urea Nitrogen (BUN)
• Normal range: 7-18 mg./dL
Elevated in ↑amino acid catabolism
↑Glutamate  ↑N-acetylglutamate 
↑CPS-1 activation
Elevated in renal insufficiency
Decreased in hepatic failure

Contenu connexe

Tendances

Lipids by Dr Ripudaman,Assistant Professor ,Anjuman Islam School of Pharmacy ...
Lipids by Dr Ripudaman,Assistant Professor ,Anjuman Islam School of Pharmacy ...Lipids by Dr Ripudaman,Assistant Professor ,Anjuman Islam School of Pharmacy ...
Lipids by Dr Ripudaman,Assistant Professor ,Anjuman Islam School of Pharmacy ...
Ripudaman Manjitsingh
 
Hexose monophosphate shunt
Hexose monophosphate shuntHexose monophosphate shunt
Hexose monophosphate shunt
Khalid Hussain
 

Tendances (20)

Lipids by Dr Ripudaman,Assistant Professor ,Anjuman Islam School of Pharmacy ...
Lipids by Dr Ripudaman,Assistant Professor ,Anjuman Islam School of Pharmacy ...Lipids by Dr Ripudaman,Assistant Professor ,Anjuman Islam School of Pharmacy ...
Lipids by Dr Ripudaman,Assistant Professor ,Anjuman Islam School of Pharmacy ...
 
Biological oxidation and oxidative phosphorylation
Biological oxidation and oxidative phosphorylationBiological oxidation and oxidative phosphorylation
Biological oxidation and oxidative phosphorylation
 
Hexose monophosphate shunt
Hexose monophosphate shuntHexose monophosphate shunt
Hexose monophosphate shunt
 
Urea cycle
Urea cycleUrea cycle
Urea cycle
 
Fatty acids
Fatty acidsFatty acids
Fatty acids
 
Heteropolysaccharides which are glycosaminoglycans and glycoconjugates
Heteropolysaccharides which are glycosaminoglycans and glycoconjugatesHeteropolysaccharides which are glycosaminoglycans and glycoconjugates
Heteropolysaccharides which are glycosaminoglycans and glycoconjugates
 
LIPID CHEMISTRY
LIPID CHEMISTRYLIPID CHEMISTRY
LIPID CHEMISTRY
 
Cholesterol
CholesterolCholesterol
Cholesterol
 
TRANSAMINATION & DEAMINATION
TRANSAMINATION & DEAMINATIONTRANSAMINATION & DEAMINATION
TRANSAMINATION & DEAMINATION
 
Pufa 2 ppt2 (6)
Pufa 2 ppt2 (6)Pufa 2 ppt2 (6)
Pufa 2 ppt2 (6)
 
Lipids - Biochemistry
 Lipids - Biochemistry  Lipids - Biochemistry
Lipids - Biochemistry
 
De Novo synthesis of fatty acids
De Novo synthesis of fatty acidsDe Novo synthesis of fatty acids
De Novo synthesis of fatty acids
 
Amino acids and Structure of Proteins
Amino acids and Structure of ProteinsAmino acids and Structure of Proteins
Amino acids and Structure of Proteins
 
Chemistry of Lipids
Chemistry of LipidsChemistry of Lipids
Chemistry of Lipids
 
VITAMIN D
VITAMIN D VITAMIN D
VITAMIN D
 
Carbohydrates
CarbohydratesCarbohydrates
Carbohydrates
 
TCA cycle- steps, regulation and significance
TCA cycle- steps, regulation and significanceTCA cycle- steps, regulation and significance
TCA cycle- steps, regulation and significance
 
Triglyceride metabolism
Triglyceride metabolismTriglyceride metabolism
Triglyceride metabolism
 
BETA-OXIDATION OF FATTY ACIDS
BETA-OXIDATION OF FATTY ACIDSBETA-OXIDATION OF FATTY ACIDS
BETA-OXIDATION OF FATTY ACIDS
 
Carbohydrate Chemistry
Carbohydrate ChemistryCarbohydrate Chemistry
Carbohydrate Chemistry
 

En vedette

Class 4 reactions of amino acid metabolism
Class 4 reactions  of  amino  acid  metabolismClass 4 reactions  of  amino  acid  metabolism
Class 4 reactions of amino acid metabolism
Dhiraj Trivedi
 
Aromatic amino acid metabolism by dr.anita verma
Aromatic amino acid metabolism by dr.anita vermaAromatic amino acid metabolism by dr.anita verma
Aromatic amino acid metabolism by dr.anita verma
sp medical coolege
 
Nitrogen Cycle
Nitrogen CycleNitrogen Cycle
Nitrogen Cycle
shabeel pn
 

En vedette (13)

Part2 dental Amino Acid Metabolism 2012-1
Part2 dental Amino Acid Metabolism 2012-1Part2 dental Amino Acid Metabolism 2012-1
Part2 dental Amino Acid Metabolism 2012-1
 
ProteinMetbolism part1
ProteinMetbolism part1ProteinMetbolism part1
ProteinMetbolism part1
 
Class 4 reactions of amino acid metabolism
Class 4 reactions  of  amino  acid  metabolismClass 4 reactions  of  amino  acid  metabolism
Class 4 reactions of amino acid metabolism
 
Metabolism of amino acids (general metabolism)
Metabolism of amino acids (general metabolism)Metabolism of amino acids (general metabolism)
Metabolism of amino acids (general metabolism)
 
Amino acids & proteins
Amino acids & proteinsAmino acids & proteins
Amino acids & proteins
 
Aromatic amino acid metabolism by dr.anita verma
Aromatic amino acid metabolism by dr.anita vermaAromatic amino acid metabolism by dr.anita verma
Aromatic amino acid metabolism by dr.anita verma
 
Protein metabolism
Protein metabolismProtein metabolism
Protein metabolism
 
Biochemistry ii protein (metabolism of amino acids) (new edition)
Biochemistry ii protein (metabolism of amino acids) (new edition)Biochemistry ii protein (metabolism of amino acids) (new edition)
Biochemistry ii protein (metabolism of amino acids) (new edition)
 
Nitrogen Cycle
Nitrogen CycleNitrogen Cycle
Nitrogen Cycle
 
Amino Acids metabolism
Amino Acids metabolismAmino Acids metabolism
Amino Acids metabolism
 
Amino acid catabolism- Part-1
Amino acid catabolism- Part-1Amino acid catabolism- Part-1
Amino acid catabolism- Part-1
 
Amino acid metabolism
Amino acid metabolismAmino acid metabolism
Amino acid metabolism
 
Amino acids metabolism new
Amino acids metabolism newAmino acids metabolism new
Amino acids metabolism new
 

Similaire à Part1 dental Amino Acid Metabolism 2012

Lec12 ureacyc
Lec12 ureacycLec12 ureacyc
Lec12 ureacyc
dream10f
 
Urea cycle for Medical students Dr veerendra
Urea cycle for Medical students  Dr veerendraUrea cycle for Medical students  Dr veerendra
Urea cycle for Medical students Dr veerendra
Veerendra Kumar Arumalla
 
Unit 8_AA oxidation and urea cycle_2023.pdf
Unit 8_AA oxidation and urea cycle_2023.pdfUnit 8_AA oxidation and urea cycle_2023.pdf
Unit 8_AA oxidation and urea cycle_2023.pdf
217208ViNgcAnh
 
Chapt08 lecture
Chapt08 lectureChapt08 lecture
Chapt08 lecture
cdobrow
 

Similaire à Part1 dental Amino Acid Metabolism 2012 (20)

Urea cycle.ppt
Urea cycle.pptUrea cycle.ppt
Urea cycle.ppt
 
Lec12 ureacyc
Lec12 ureacycLec12 ureacyc
Lec12 ureacyc
 
Amino acid metabolism
Amino acid metabolismAmino acid metabolism
Amino acid metabolism
 
Amino acid metabolism
Amino acid metabolismAmino acid metabolism
Amino acid metabolism
 
notes for amino acids nd their classification .ppt
notes for amino acids nd their classification .pptnotes for amino acids nd their classification .ppt
notes for amino acids nd their classification .ppt
 
urea- tca cycle(0).pdf
urea- tca cycle(0).pdfurea- tca cycle(0).pdf
urea- tca cycle(0).pdf
 
Urea cycle for Medical students Dr veerendra
Urea cycle for Medical students  Dr veerendraUrea cycle for Medical students  Dr veerendra
Urea cycle for Medical students Dr veerendra
 
Protein Metabolism for First BDS students.
Protein Metabolism for First BDS students.Protein Metabolism for First BDS students.
Protein Metabolism for First BDS students.
 
Mayur metabolism/certified fixed orthodontic courses by Indian dental academy
Mayur metabolism/certified fixed orthodontic courses by Indian dental academyMayur metabolism/certified fixed orthodontic courses by Indian dental academy
Mayur metabolism/certified fixed orthodontic courses by Indian dental academy
 
Unit 8_AA oxidation and urea cycle_2023.pdf
Unit 8_AA oxidation and urea cycle_2023.pdfUnit 8_AA oxidation and urea cycle_2023.pdf
Unit 8_AA oxidation and urea cycle_2023.pdf
 
Msb 206. amino acid catab and fates of cs.2014
Msb 206. amino acid catab and fates of cs.2014Msb 206. amino acid catab and fates of cs.2014
Msb 206. amino acid catab and fates of cs.2014
 
Chapt08 lecture
Chapt08 lectureChapt08 lecture
Chapt08 lecture
 
Amino acids metabolism.ppt
Amino acids                metabolism.pptAmino acids                metabolism.ppt
Amino acids metabolism.ppt
 
Urea
UreaUrea
Urea
 
Biochemistry high yield points by GIMS
Biochemistry high yield points by GIMSBiochemistry high yield points by GIMS
Biochemistry high yield points by GIMS
 
Amino Acid Metabolism
Amino Acid MetabolismAmino Acid Metabolism
Amino Acid Metabolism
 
Individual path of aminoacids
Individual path of aminoacidsIndividual path of aminoacids
Individual path of aminoacids
 
TCA cycle citric acid cycle krebs cycle.
TCA cycle citric acid cycle krebs cycle.TCA cycle citric acid cycle krebs cycle.
TCA cycle citric acid cycle krebs cycle.
 
Amino acid
Amino acidAmino acid
Amino acid
 
Urea Cycle or Ornithine Cycle- Function,Reactions,Regulation,GENERAL ABBREVIA...
Urea Cycle or Ornithine Cycle- Function,Reactions,Regulation,GENERAL ABBREVIA...Urea Cycle or Ornithine Cycle- Function,Reactions,Regulation,GENERAL ABBREVIA...
Urea Cycle or Ornithine Cycle- Function,Reactions,Regulation,GENERAL ABBREVIA...
 

Plus de IAU Dent

Plus de IAU Dent (20)

Odontogenic Infection
Odontogenic InfectionOdontogenic Infection
Odontogenic Infection
 
Odontogenic Tumors
Odontogenic TumorsOdontogenic Tumors
Odontogenic Tumors
 
Maxillofacial injuries
Maxillofacial injuriesMaxillofacial injuries
Maxillofacial injuries
 
Impacted teeth
Impacted teethImpacted teeth
Impacted teeth
 
Odontogenic Cysts
Odontogenic CystsOdontogenic Cysts
Odontogenic Cysts
 
Chronic gingivitis
Chronic gingivitisChronic gingivitis
Chronic gingivitis
 
Plaque control
Plaque controlPlaque control
Plaque control
 
8. hypotension & hypertension
8. hypotension & hypertension8. hypotension & hypertension
8. hypotension & hypertension
 
8. Prescription Writing
8. Prescription Writing8. Prescription Writing
8. Prescription Writing
 
7. Adrenocorticosteriods
7. Adrenocorticosteriods7. Adrenocorticosteriods
7. Adrenocorticosteriods
 
7.a. histamine & antihistaminics
7.a. histamine & antihistaminics7.a. histamine & antihistaminics
7.a. histamine & antihistaminics
 
8 anticancer drugs
8  anticancer drugs8  anticancer drugs
8 anticancer drugs
 
7 antibiotic-dental
7 antibiotic-dental7 antibiotic-dental
7 antibiotic-dental
 
7.b. sedative hypnotics
7.b. sedative hypnotics 7.b. sedative hypnotics
7.b. sedative hypnotics
 
6. peptic ulcer drugs 323
6. peptic ulcer drugs 3236. peptic ulcer drugs 323
6. peptic ulcer drugs 323
 
6. anti drenergic
6. anti drenergic 6. anti drenergic
6. anti drenergic
 
6 beta lactum drugs dental
6  beta lactum drugs dental6  beta lactum drugs dental
6 beta lactum drugs dental
 
4.anti colinergic
4.anti colinergic 4.anti colinergic
4.anti colinergic
 
5 aminoglycosides,macrolides, anti tb dental
5 aminoglycosides,macrolides, anti tb dental5 aminoglycosides,macrolides, anti tb dental
5 aminoglycosides,macrolides, anti tb dental
 
5. opioid analgesics
5. opioid analgesics5. opioid analgesics
5. opioid analgesics
 

Dernier

Call Girls Bhubaneswar Just Call 9907093804 Top Class Call Girl Service Avail...
Call Girls Bhubaneswar Just Call 9907093804 Top Class Call Girl Service Avail...Call Girls Bhubaneswar Just Call 9907093804 Top Class Call Girl Service Avail...
Call Girls Bhubaneswar Just Call 9907093804 Top Class Call Girl Service Avail...
Dipal Arora
 

Dernier (20)

Call Girls Service Jaipur {9521753030} ❤️VVIP RIDDHI Call Girl in Jaipur Raja...
Call Girls Service Jaipur {9521753030} ❤️VVIP RIDDHI Call Girl in Jaipur Raja...Call Girls Service Jaipur {9521753030} ❤️VVIP RIDDHI Call Girl in Jaipur Raja...
Call Girls Service Jaipur {9521753030} ❤️VVIP RIDDHI Call Girl in Jaipur Raja...
 
Call Girls Agra Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Agra Just Call 8250077686 Top Class Call Girl Service AvailableCall Girls Agra Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Agra Just Call 8250077686 Top Class Call Girl Service Available
 
Call Girls Jabalpur Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Jabalpur Just Call 8250077686 Top Class Call Girl Service AvailableCall Girls Jabalpur Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Jabalpur Just Call 8250077686 Top Class Call Girl Service Available
 
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
 
Call Girls Nagpur Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Nagpur Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Nagpur Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Nagpur Just Call 9907093804 Top Class Call Girl Service Available
 
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
 
Pondicherry Call Girls Book Now 9630942363 Top Class Pondicherry Escort Servi...
Pondicherry Call Girls Book Now 9630942363 Top Class Pondicherry Escort Servi...Pondicherry Call Girls Book Now 9630942363 Top Class Pondicherry Escort Servi...
Pondicherry Call Girls Book Now 9630942363 Top Class Pondicherry Escort Servi...
 
Call Girls Bhubaneswar Just Call 9907093804 Top Class Call Girl Service Avail...
Call Girls Bhubaneswar Just Call 9907093804 Top Class Call Girl Service Avail...Call Girls Bhubaneswar Just Call 9907093804 Top Class Call Girl Service Avail...
Call Girls Bhubaneswar Just Call 9907093804 Top Class Call Girl Service Avail...
 
Call Girls Tirupati Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Tirupati Just Call 8250077686 Top Class Call Girl Service AvailableCall Girls Tirupati Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Tirupati Just Call 8250077686 Top Class Call Girl Service Available
 
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
 
Best Rate (Guwahati ) Call Girls Guwahati ⟟ 8617370543 ⟟ High Class Call Girl...
Best Rate (Guwahati ) Call Girls Guwahati ⟟ 8617370543 ⟟ High Class Call Girl...Best Rate (Guwahati ) Call Girls Guwahati ⟟ 8617370543 ⟟ High Class Call Girl...
Best Rate (Guwahati ) Call Girls Guwahati ⟟ 8617370543 ⟟ High Class Call Girl...
 
Call Girls Guntur Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Guntur  Just Call 8250077686 Top Class Call Girl Service AvailableCall Girls Guntur  Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Guntur Just Call 8250077686 Top Class Call Girl Service Available
 
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
 
Premium Bangalore Call Girls Jigani Dail 6378878445 Escort Service For Hot Ma...
Premium Bangalore Call Girls Jigani Dail 6378878445 Escort Service For Hot Ma...Premium Bangalore Call Girls Jigani Dail 6378878445 Escort Service For Hot Ma...
Premium Bangalore Call Girls Jigani Dail 6378878445 Escort Service For Hot Ma...
 
Best Rate (Hyderabad) Call Girls Jahanuma ⟟ 8250192130 ⟟ High Class Call Girl...
Best Rate (Hyderabad) Call Girls Jahanuma ⟟ 8250192130 ⟟ High Class Call Girl...Best Rate (Hyderabad) Call Girls Jahanuma ⟟ 8250192130 ⟟ High Class Call Girl...
Best Rate (Hyderabad) Call Girls Jahanuma ⟟ 8250192130 ⟟ High Class Call Girl...
 
Call Girls Gwalior Just Call 8617370543 Top Class Call Girl Service Available
Call Girls Gwalior Just Call 8617370543 Top Class Call Girl Service AvailableCall Girls Gwalior Just Call 8617370543 Top Class Call Girl Service Available
Call Girls Gwalior Just Call 8617370543 Top Class Call Girl Service Available
 
O898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In Ahmedabad
O898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In AhmedabadO898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In Ahmedabad
O898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In Ahmedabad
 
Call Girls Kochi Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Kochi Just Call 8250077686 Top Class Call Girl Service AvailableCall Girls Kochi Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Kochi Just Call 8250077686 Top Class Call Girl Service Available
 
Top Rated Bangalore Call Girls Richmond Circle ⟟ 9332606886 ⟟ Call Me For Ge...
Top Rated Bangalore Call Girls Richmond Circle ⟟  9332606886 ⟟ Call Me For Ge...Top Rated Bangalore Call Girls Richmond Circle ⟟  9332606886 ⟟ Call Me For Ge...
Top Rated Bangalore Call Girls Richmond Circle ⟟ 9332606886 ⟟ Call Me For Ge...
 
Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...
Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...
Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...
 

Part1 dental Amino Acid Metabolism 2012

  • 2. OVERVIEW OF CENTRAL AMINO ACID METABOLISM ENVIRONMENT ORGANISM Ingested Diatary proteins 70-100g/d Bio- synthesis Body Proteins 35-200g/d AMINO ACIDS Nitrogen (NH3) Carbon skeletons (Keto- acids) Urea Degradation (required) 1 2 3 a b Purines Pyrimidines Porphyrins (heme) Niacin Neurotansmitters Polyamines c c Used for energy pyruvate α-ketoglutarate succinyl-CoA fumarate oxaloacetate acetoacetate acetyl CoA (glucogenic) (ketogenic) CO2 + Water
  • 3. Metabolic Classification of the Amino Acids • Based on synthesis: Essential and Non-essential • Based on degradation (Fate): Glucogenic and Ketogenic Essential Amino Acids in Humans • Required in diet • Human is incapable of forming their requisite carbon skeleton Non-essential Amino Acids in Humans • Not required in diet • Can be formed from α-keto acids by transamination and subsequent reactions • Valine • Leucine • Isoleucine • Methionine • Phenylalanine •Tryptophan • Threonine •Histidine* • Lysine •Glycine •Alanine •Proline •Tyrosine* •Serine •Cysteine* •Glutamine •Asparagine •Glutamate •Aspartate •Arginine*
  • 4. DEGRADATION (FATE) OF THE CARBON SKELETONS Carbon skeletons are used for energy. Glucogenic Amino Acids: degradead to TCA cycle intermediates Oxaloacetate, Fumarate,Succinyl CoA, α-ketoglutarate, or pyruvate (gluconeogensis). Ketogenic Amino Acids: degraded to acetyl CoA, acetoacetyl CoA, or acetoacetate ( form ketone bodies).
  • 5. AMINO ACID DEGRADATION INTERMEDIATESAMINO ACID DEGRADATION INTERMEDIATES CO2 CO2 Pyruvate Acetyl-CoA Acetoacetate Citrate Isocitrate -ketoglutarate Succinyl-CoA Fumarate Oxaloacetate Citric Acid Cycle CO2 Glucose Ala Ser Cys Thr* Gly Trp* Ile* Leu• Lys• Thr* Leu• Trp* Lys• Tyr* Phe* Asn Asp Asp Phe* Tyr* Ile* Met Val Arg His Glu Pro Gln Glucogenic Ketogenic * Both Glucogenic and Ketogenic • Purely Ketogenic PEP Malate Succinate
  • 6. Incorporation of NH4 + Into Organic Compounds 1) NH4 + + HCO3 - + 2 ATP NH2CO2PO3 -2 + 2 ADP + Carbamoyl Phosphate Pi + 2 H+ 2) NH4 + + Carbamoyl Phosphate Synthetase I (CPS-I) Glutamate dehydrogenase O - O2CCH2CH2CCO 2 - -Ketoglutarate Glutamate NADP +NADPH + H+ NH3 + - O2CCH2CH2CHCO 2 - TCA Cycle Incorporation of NH4 + Into Organic Compounds (Cont.) NH3 + - O2CCH2CH2CHCO 2 - + NH4 + + 2 ATP NH3 +O H2NCCH2CH2CHCO 2 - Glutamine Glutamate Glutamine Synthetase Mg++ N of glutamine donated to other compounds in synthesis of purines, pyrimidines, and other amino acids 3)
  • 7. Biosynthesis of Amino Acids *Transaminations: Amino Acid1 +α-Keto Acid2  Amino Acid2 +α-Keto Acid1 + O R-CCO 2 - Glutamate Pyridoxal phosphate (PLP)- Dependent Aminotransferase + α- Ketoglutarate Biosynthesis of Essential Amino Acids Their -ketoacids are not common intermediates (enzymes needed to form them are lacking) so transamination is not an option. Biosynthesis of Non-essential Amino Acids Transamination of -ketoacids that are available as common intermediates. (treatment of hyperamonemia) All (except Tyr) synthesized from the common intermediates synthesized in cell : • Pyruvate • Oxaloacetate • -ketoglutarate • 3-phosphoglycerate NH3 + - O2CCH2CH2CHCO 2 - NH2 R-CHCO 2 - O - O2CCH2CH2CCO 2 -
  • 8. Transamination Reactions : One Step Pyruvate + AA  Alanine + -ketoacid Oxaloacetate + AA Aspartate + -ketoacid -ketoglutarate + AA Glutamate + -ketoacid Transaminases: Equilibrate amino groups among -ketos. Require pyridoxal phosphte (PLP). Blood transaminases has a diagnostic value. (AST or GOT , ALT or GPT) All AAs, except Lys and Thr, can be transaminated. Most transaminases generate Glu or Asp. *ATP-dependent amidation of Glu, Asp:  GLU + ATP + NH3  GLN + ADP + Pi By the nnzyme glutamine synthetase Where NH3 is toxic ; stored as Gln. Gln donates amino gps in many reactions  ASP + ATP + GLN  ASN + AMP + PPi + GLU By the enzyme Asparagine synthetase. Low in some cell tumor types. ( Asparaginase treatment ) .
  • 9. Transaminations Glutamate -Ketoglutarate + + Pyruvate Alanine Glutamate -Ketoglutarate + + Oxaloacetate Aspartate Glutamate-Pyruvate Aminotransferase (Alanine Transferase ALT) Glutamate-Oxaloacetate Aminotransferase (Aspartate Transferase AST) Blood levels of these aminotransferases, also called transaminases, are important indicators of liver disease
  • 10. AAMMIINNOO AACCIIDD CCAATTAABBOOLLIISSMM AA.. NNiittrrooggeenn ((NNHH3)) H2N C O NH2 urea Most terrestrial land animals convert excess nitrogen to urea, prior to excreting it. Urea is less toxic than ammonia. The Urea Cycle occurs mainly in liver excreted by kidney. The 2 nitrogen atoms of urea enter the Urea Cycle as NH3 (produced mainly via Glutamate Dehydrogenase) and as the amino N of aspartate. The NH3 and HCO3 (carbonyl C) that will be part of urea are incorporated first into carbamoyl phosphate.
  • 11. Carbamoyl Phosphate Synthetase is the committed step of the Urea Cycle, and is subject to regulation. H2N C OPO3 2 O HCO3  + NH3 + 2 ATP + 2 ADP + Pi Carbamoyl Phosphate Synthetase carbamoyl phosphate N H C COO CH2 CH2 COO H CH3C O N-acetylglutamate H3N+ C COO CH2 CH2 COO H glutamate (Glu) Carbamoyl Phosphate Synthetase has an absolute requirement for an allosteric activator N-acetylglutamate. This derivative of glutamate is synthesized from acetyl-CoA & glutamate when cellular [glutamate] is high, signaling an excess of free amino acids due to protein breakdown or dietary intake.
  • 12. H2N C OPO3 2 O CH2 CH2 CH2 HC COO NH3 + NH3 + CH2 CH2 CH2 HC COO NH3 + NH CO NH2 COO CH2 HC COO NH2 CH2 CH2 CH2 HC COO NH3 + NH C NH2 + COO CH2 HC COO H N AMP + PPi ATP CH2 CH2 CH2 HC COO NH3 + NH C NH2 + H2N COO HC CH COO  C NH2H2N O H2O Pi ornithine urea citrulline aspartate arginino- succinate fumarate arginine carbamoyl phosphate Urea Cycle 1 2 3 4 Urea Cycle -Enzymes in mitochondria: 1. Ornithine Trans- carbamylase -Enzymes in cytosol: 2. Arginino- Succinate Synthetase 3. Arginino- succinase 4. Arginase.
  • 13. Fumarate is converted to oxaloacetate via Krebs Cycle. Oxaloacetate is converted to aspartate via transamination (e.g., from glutamate). Aspartate then reenters Urea Cycle, carrying an amino group derived from another amino acid. aspartate -ketoglutarate oxaloacetate glutamate Aminotransferase (Transaminase) COO CH2 CH2 C COO O COO CH2 HC COO NH3 + COO CH2 CH2 HC COO NH3 + COO CH2 C COO O+ +
  • 14. Hereditary deficiency of any of the Urea Cycle enzymes leads to hyperammonemia - elevated [ammonia] in blood. Total lack of any Urea Cycle enzyme is lethal. Elevated ammonia is toxic, especially to the brain. If not treated immediately after birth, severe mental retardation results. Postulated mechanisms for toxicity of high [ammonia]: 1. High [NH3] would drive Glutamine Synthetase: glutamate + ATP + NH3  glutamine + ADP + Pi This would deplete glutamate – a neurotransmitter & precursor for synthesis of the neurotransmitter GABA (later) . 2. Depletion of glutamate & high ammonia level would drive Glutamate Dehydrogenase reaction to reverse: glutamate + NAD(P)+ α-ketoglutarate + NAD(P)H + NH4 + The resulting depletion of α-ketoglutarate, an essential Krebs Cycle intermediate, could impair energy metabolism in the brain. Deficiencies related to Urea Cycle Carbamoyl Phosphate Synthetase Deficiency and N-acetylglutamate synthetase Deficiency Ornithine Transcarbamoylase Dificiency Argininosuccinate Synthetase and Lyase Deficiencies Arginase Deficiency
  • 15. • Blood Urea Nitrogen (BUN) • Normal range: 7-18 mg./dL Elevated in ↑amino acid catabolism ↑Glutamate  ↑N-acetylglutamate  ↑CPS-1 activation Elevated in renal insufficiency Decreased in hepatic failure