SlideShare a Scribd company logo
1 of 71
CHAPTER 19 
Amino Acid Oxidation 
Production of Urea 
Key topics: 
– How proteins are digested in animals 
– How amino acids are degraded in animals 
– How urea is made and excreted
Oxidation of Amino Acids is a Significant 
Energy-Yielding Pathway in Carnivores 
• Not all organisms use amino acids as the source 
of energy 
• About 90% of energy needs of carnivores can be 
met by amino acids immediately after a meal 
• Only a small fraction of energy needs of 
herbivores are met by amino acids 
• Microorganisms scavenge amino acids from their 
environment for fuel
Sources and Uses of Amino Acids 
Sources 
1.Proteins in the diet provide both essential and non-essential 
amino acids in contrast to microorganisms that 
for the most part synthesize their own. 
2.Turnover of endogenous proteins 
3.de novo biosynthesis (non-essential amino acids) 
Uses 
1.Protein synthesis 
2.Nitrogen and carbon source of general and special 
product biosynthesis 
3.Energy source 
a.glucogenic (those that can be used for the synthesis of glucose) 
b.ketogenic (those whose metabolism leads to ketone bodies)
Metabolic Circumstances of 
Amino Acid Oxidation 
Amino acids undergo oxidative catabolism 
under three circumstances: 
– Protein amino-acid residues from normal turnover 
are recycled to generate energy and molecular 
components 
– Dietary amino acids that exceed body’s protein 
synthesis needs are degraded 
– Proteins in the body are broken down to supply 
amino acids for catabolism when carbohydrates 
are in short supply (starvation, diabetes mellitus),
Protein Turnover and Nitrogen 
Balance 
Protein Degradation: 
• Endogenous proteins degrade continuously 
- Damaged 
- Mis-folded 
- Un-needed 
• Dietary protein intake - mostly degraded 
Nitrogen Balance - expresses the patient’s current 
status - are they gaining or losing net Nitrogen?
Dietary Proteins are 
Enzymatically Hydrolyzed 
• Pepsin cuts protein into peptides in the stomach 
• Trypsin and chymotrypsin cut proteins and larger 
peptides into smaller peptides in the small 
intestine 
• Aminopeptidase and carboxypeptidases A and B 
degrade peptides into amino acids in the small 
intestine
stomach pancreas to 
small intestine 
intestinal 
wall 
pepsin Trypsin 
Chymotrypsin 
carboxypeptidase A 
carboxypeptidase B 
elastase 
dipeptidases
Enzymatic 
Degradation of 
Dietary Proteins 
• (a) gastrin -> secretion of 
HCl by parietal cells and 
pepsin by chief cells 
• (b) exocrine cells synthesize 
zymogens 
– zymogen granules fuse with 
plasma membrane 
– zymogens released into the 
lumen of the collecting duct 
– collecting ducts -> pancreatic 
duct -> small intestine. 
• (c) Amino acids -> villi -> 
capillaries
Overview 
of Amino 
Acid 
Catabolism
OVERVIEW OF AMINO ACID METABOLISM 
ENVIRONMENT ORGANISM 
Ingested 
protein 
Bio-synthesis 
Protein 
1 2 3 
AMINO 
ACIDS 
Nitrogen Carbon 
skeletons 
Urea 
Degradation 
(required) 
a 
b 
Purines 
Pyrimidines 
Porphyrins 
c c 
(ketogenic) (glucogenic) 
Used for 
energy pyruvate 
α-ketoglutarate 
succinyl-CoA 
fumarate 
oxaloacetate 
acetoacetate 
acetyl CoA
Degradation of amino acids to one of 
seven common metabolic intermediates.
Amino acid metabolism 
• Metabolism of amino acids differs, but 3 
common reactions: 
– Transamination 
– Deamination 
– Formation of urea
Typical first transamination reaction: 
The usual AA acceptor is α-ketoglutarate, producing 
GLUTAMATE and the new a-keto acid. 
Transamination is a reaction between an amino acid and 
a keto-acid in which the amino group is transferred from 
the donor amino acid onto the acceptor keto-acid.
TRANSAMINATION
Enzymatic Transamination 
• Typically, a-ketoglutarate 
accepts amino groups 
• L-Glutamine acts as a 
temporary storage of nitrogen 
• L-Glutamine can donate the 
amino group when needed for 
amino acid biosynthesis 
• All aminotransferases rely on 
the pyridoxal phosphate (PLP) 
cofactor
Structure of Pyridoxal Phosphate 
and Pyridoxamine Phosphate 
• Intermediate, enzyme-bound 
carrier of 
amino groups 
• Aldehyde form can 
react reversibly with 
amino groups 
• Aminated form can 
react reversibly with 
carbonyl groups
A small number of amino acids undergo 
oxidative or non-oxidative deamination
18 
Urea Formation 
• Occurs primarily in liver; excreted by kidney 
• Principal method for removing ammonia 
• Hyperammonemia: 
• Defects in urea cycle enzymes 
• Severe neurological defects in neonates
Treatment of deficiency of Urea Cycle enzymes (depends 
on which enzyme is deficient): 
 limiting protein intake to the amount barely adequate 
to supply amino acids for growth, while adding to the 
diet the a-keto acid analogs of essential amino acids. 
 Liver transplantation has also been used, since liver 
is the organ that carries out Urea Cycle. 
 Dialysis 
 Increase ammonia excretion: Na benzoate, Na 
phenylbutyrate, L-arginine, L-citrulline
Postulated mechanisms for toxicity of high 
[ammonia]: 
1. High [NH3] would drive Glutamine Synthase: 
glutamate + ATP + NH3  glutamine + ADP + Pi 
This would deplete glutamate – a neurotransmitter & 
precursor for synthesis of the neurotransmitter GABA. 
2. Depletion of glutamate & high ammonia level would drive 
Glutamate Dehydrogenase reaction to reverse: 
glutamate + NAD(P)+ a-ketoglutarate + 
NAD(P)H + NH4 
+ 
The resulting depletion of a-ketoglutarate, an essential 
Krebs Cycle intermediate, could impair energy metabolism 
in the brain.
21 
GABA Formation 
NH3 
+ 
-O2CCH2CH2CHCO2 
- 
NH3 
+ 
-O2CCH2CH2CH2 
Glutamate 
decarboxylase 
Glutamate Gamma-aminobutyrate 
(GABA) 
CO2 
GABA is an important inhibitory neurotransmitter in the brain 
Drugs (e.g., benzodiazepines) that enhance the effects 
of GABA are useful in treating epilepsy
• Glutamate is the precursor of free GABA in GABAergic terminals and 
comes from two different sources (Kreb's cycle in glia cells and 
glutamine in nerve terminals). Next, the enzyme glutamic acid 
decarboxylase (GAD) forms GABA from glutamate. After being 
released into the synapses, GABA is inactivated by reuptake mediated 
by GABA transporters (GATs) into presynaptic terminals or into glia 
cells where it is metabolized by GABA-transaminase (GABA-T).
NN bbaallaannccee == NNiinn -- NNoouutt 
1 Major dietary source of N is Protein (>95%), since the 
diet has very few free amino acids (AA) 
2 AA are used for Protein Synthesis & N containing 
compounds 
3 AA in excess are degraded (used for energy) 
N is disposed of in urea (80%), ammonia, uric acid or 
creatinine in urine with small amounts in fecal matter 
(undigested)
Nitrogen Acquisition 
• Nitrogen Fixation 
• Nitrate Assimilation 
• Ammonium Assimilation
N2 is converted to metabolically 
useful forms (is "fixed") only by a 
few species of prokaryotes, called 
Diazotrophs. 
Diazotrophs of the genus 
Rhizobium live symbiotically in the 
root nodules of legumes, where 
they convert N2 to NH3 (ammonia) 
in a process called 
NITROGEN FIXATION: 
NITROGENASE 
N2 + 8 H+ + 8 e- + 16 ATP + 16 H2O → 2 NH3 + H2 + 16 ADP + 16 Pi
* But, less than 1% of N entering the biosphere comes from N 
fixation. 
Another oxidized form of nitrogen, NO3 
- (nitrate ion) is also 
found in the soils and oceans. 
It is converted to NH4 
+ through NITRATE ASSIMILATION: 
* The reduction of NO3 
- to NH4 
+ (ammonium ion) occurs in 
green plants, various fungi, and certain bacteria in a two-step 
p(1a) tThhew 2a-eyl:ectron reduction of nitrate to nitrite: 
NO3 
- + 2 H+ + 2 e- → NO2 
- + H2O ( catalyzed by nitrate reductase) 
(2) This is followed by the 6-electron reduction of nitrite to ammonium: 
NO2 
- + 8 H+ + 6 e- → NH4 
+ + 2 H2O ( catalyzed by nitrite reductase) 
*NH3/NH4 
+ can be incorporated into the amino acids glutamate 
by glutamate dehydrogenase (and glutamine by glutamine 
synthetase.
Nitrate Assimilation 
(Green plants, some fungi and bacteria) 
NO3 
– + NADH + H+ NO2 
– + H2O + NAD+ 
Nitrate Reductase 
NO2 
– + 8H+ + 6e– NH4 
+ + 2H2O 
Nitrite Reductase
Ammonium Assimilation 
(Carbamoyl Phosphate Synthetase) 
O 
H2N C 
OP 
2ATP 2ADP+Pi 
– 
NH3 + HCO3 
(Biosynthetic Glutamate Dehydrogenase) 
and/or 
(Glutamine Synthetase) 
NH3 Glutamate 
NH3 
Glutamine
No animals are capable of either N-fixation or 
nitrate assimilation, so animals are totally 
dependent on plants and microorganisms for 
the synthesis of organic nitrogenous 
compounds, such as amino acids and proteins, 
to provide this essential nutrient.
Nitrogen balance 
• Protein content of adult body remains remarkably constant 
– Protein constitutes 10-15% of diet 
• Equivalent amount of amino acids must be lost each day 
Nitrogen balance = nitrogen ingested - nitrogen excreted 
(primarily as protein) (primarily as urea) 
Nitrogen balance = 0 (nitrogen equilibrium) 
protein synthesis = protein degradation 
Positive nitrogen balance 
protein synthesis > protein degradation 
Negative nitrogen balance 
protein synthesis < protein degradation
Fates of Nitrogen in Organisms 
• Plants conserve almost all the nitrogen 
• Many aquatic vertebrates release ammonia to their 
environment 
– Passive diffusion from epithelial cells 
– Active transport via gills 
• Many terrestrial vertebrates and sharks excrete nitrogen 
in the form of urea 
– Urea is far less toxic that ammonia 
– Urea has very high solubility 
• Some animals, such as birds and reptiles excrete 
nitrogen as uric acid 
– Uric acid is rather insoluble 
– Excretion as paste allows to conserve water 
• Humans and great apes excrete both urea (from amino 
acids) and uric acid (from purines)
Excretory 
Forms of 
Nitrogen
The Amino 
Group is 
Removed From 
All Amino Acids 
First
Glutamate can Donate 
Ammonia to Pyruvate to 
Make Alanine 
• Vigorously working muscles 
operate nearly anaerobically 
and rely on glycolysis for 
energy 
• Glycolysis yields pyruvate that 
muscles cannot metabolize 
aerobically; if not eliminated 
lactic acid will build up 
• This pyruvate can be 
converted to alanine for 
transport into liver
Ammonia in 
Transported in the 
Bloodstream Safely 
as Glutamate 
• Un-needed glutamine 
is processed in 
intestines, kidneys 
and liver
Excess Glutamate is Metabolized in 
the Mitochondria of Hepatocytes
The Glutamate 
Dehydrogenase 
Reaction 
• Two-electron oxidation 
of glutamate followed 
by hydrolysis 
• Net process is 
oxidative deamination 
of glutamate 
• Occurs in mitochondrial 
matrix in mammals 
• Can use either NAD+ or 
NADP+ as electron 
acceptor
Nitrogen 
from 
Carbamoyl 
Phosphate 
Enters the 
Urea Cycle
Urea Cycle 
• UUrreeaa iiss pprroodduucceedd iinn tthhee lliivveerr 
• FFrroomm tthhee lliivveerr,, iitt iiss ttrraannssppoorrtteedd iinn tthhee bblloooodd ttoo tthhee kkiiddnneeyyss ffoorr 
eexxccrreettiioonn iinn uurriinnee 
UUrreeaa iiss ccoommppoosseedd ooff:: 
TTwwoo nniittrrooggeenn aattoommss 
• First nitrogen atom is from ffrreeee aammmmoonniiaa 
• Second nitrogen atom is from aassppaarrttaattee 
CCaarrbboonn && ooxxyyggeenn aattoommss aarree ffrroomm CCOO22
The Reactions in the Urea Cycle 
• 1 ornithine + carbamoyl phosphate => citrulline 
– (entry of the first amino group). 
– citrulline passes into the cytosol. 
• 2a citrulline + ATP => citrullyl-AMP + PPi 
• 2b citrullyl-AMP + Aspartate => argininosuccinate + AMP 
– (entry of the second amino group). 
• 3 argininosuccinate => arginine + fumarate 
– fumarate enters the citric acid cycle. 
• 4 arginine => urea + ornithine 
– Ornithine passes to the mitochondria to continue the cycle
Urea 
Cycle N-2 
from 
Aspartate
Ammonia is Re-captured via 
Synthesis of Carbamoyl Phosphate 
• This is the first nitrogen-acquiring reaction
Entry of Aspartate into the Urea 
Cycle 
• This is the second nitrogen-acquiring reaction
Aspartate –Argininosuccinate Shunt 
Links Urea Cycle and Citric Acid Cycle
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.
FFaattee ooff UUrreeaa 
UUrreeaa 
((ssyynntthheessiizzeedd iinn tthhee lliivveerr)) 
BBlloooodd 
KKiiddnneeyy intestine 
Urine cleaved by bacterial urease 
AAmmmmoonniiaa CO2 
In stool Reabsorbed in blood
Disposal of Ammonia 
1- UUrreeaa 
iinn tthhee lliivveerr 
• is quantitatively the mmoosstt iimmppoorrttaanntt disposal route for 
ammonia 
• Urea is formed in the lliivveerr from ammonia (urea cycle) 
• UUrreeaa travels in the blood from the liver to the kkiiddnneeyyss 
where it is filtered to appear in uurriinnee
Disposal of Ammonia 
2- GGlluuttaammiinnee 
iinn mmoosstt ppeerriipphheerraall ttiissssuueess eessppeecciiaallllyy bbrraaiinn,, SSkkeelleettaall MMuusscclleess 
&& lliivveerr 
• In most peripheral tissues, glutamate binds with aammmmoonniiaa by action of 
gglluuttaammiinnee ssyynntthhaassee 
• in the bbrraaiinn, it is the major mechanism of removal of ammonia from the 
brain 
• This structure provides a nnoonnttooxxiicc ssttoorraaggee && ttrraannssppoorrtt ffoorrmm ooff aammmmoonniiaa 
• Glutamine is transported to blood to other organs esp. liver & kidneys 
• In the liver & Kidney, glutamine is converted to ammonia & glutamate 
by the enzyme gglluuttaammiinnaassee.
Disposal of Ammonia 
3- AAllaanniinnee 
iinn sskkeelleettaall mmuusscclleess 
• AAmmmmoonniiaa + Pyruvate form aallaanniinnee in skeletal muscles 
• Alanine is transported in blood to liver 
• In liver, alanine is converted to pyruvate & aammmmoonniiaa 
• Pyruvate can be converted to gglluuccoossee (by gluconeogenesis) 
• GGlluuccoossee can enter the blood to be used by skeletal muscles 
((GGLLUUCCOOSSEE -- AALLAANNIINNEE PPAATTHHWWAAYY))
Disposal of Ammonia 
GGlluuttaammiinnee 
iinn MMoosstt TTiissssuueess 
EEsspp.. bbrraaiinn && KKiiddnneeyyss 
UUrreeaa 
iinn LLiivveerr 
AAllaanniinnee 
iinn SSkkeelleettaall MMuusscclleess
Not All Amino Acids can be 
Synthesized in Humans 
• These amino acids 
must be obtained 
as dietary protein 
• Consumption of a 
variety of foods 
(including 
vegetarian only 
diets) well supplies 
all the essential 
amino acids
Essential amino acids 
Mammalian cells lack enzymes to synthesize their carbon 
skeletons (a-keto acids). 
Isoleucine, leucine, & valine 
Lysine 
Threonine 
Tryptophan 
Phenylalanine (Tyr can be made from Phe.) 
Methionine (Cys can be made from Met.) 
Histidine (Essential for infants.)
54 
•One way to remember the 9 essential amino acids is with the 
mnemonic VF WITH MLK (Very Full With Milk): 
V Valine 
F Phenylalanine 
W Tryptophan 
I Isoleucine 
T Threonine 
H Histidine 
M Methionine 
L Leucine 
K Lysine
Fates of carbon 
skeleton of 
amino acids
Fate of Individual Amino Acids 
• Seven to acetyl-CoA 
– Leu, Ile, Thr, Lys, Phe, Tyr, Trp 
• Six to pyruvate 
– Ala, Cys, Gly, Ser, Thr, Trp 
• Five to a-ketoglutarate 
– Arg, Glu, Gln, His, Pro 
• Four to succinyl-CoA 
– Ile, Met, Thr, Val 
• Two to fumarate 
– Phe, Tyr 
• Two to oxaloacetate 
– Asp, Asn
Glucogenic vs ketogenic amino acids 
• Glucogenic amino acids 
(are degraded to pyruvate or 
citric acid cycle 
intermediates) - can supply 
gluconeogenesis pathway 
• Ketogenic amino acids (are 
degraded to acetyl CoA or 
acetoacetyl CoA) - can 
contribute to synthesis of 
fatty acids or ketone bodies 
• Some amino acids are both 
glucogenic and ketogenic
Summary of 
Amino Acid 
Catabolism
6 Amino Acids -> 
Pyruvate 
Ala, Gly, Ser, 
Cys,Trp,Thr.
7 AAs -> Acetyl CoA [W,K,F,Y, L]
I, M, T, V-> 
Succinyl-CoA
Albinism – 
genetically determined 
lack or deficit of enzyme 
tyrosinase 
Tyrosinase in 
melanocytes oxidases 
tyrosine to DOPA and 
DOPA-chinone 
tyrosinase 
Phenylalanine 
Tyrosine Tyroxine 
Melanin 
DOPA 
Dopamine 
Norepinephrine 
Epinephrine
The pathways for the biosynthesis of amino acids are diverse 
Common feature: carbon skeletons come from 
intermediates of 
 glycolysis, 
 pentose phosphate pathway, 
 citric acid cycle. 
All amino acids 
are grouped 
into families 
according to the 
intermediates 
that they are 
made from
Summary 
• Amino acids from protein are an important energy source 
in carnivorous animals 
• Catabolism of amino acids involves transfer of the amino 
group via PLP-dependent aminotransferase to a donor 
such as a-ketoglutarate to yield L-glutamine 
• L-glutamine can be used to synthesize new amino acids, 
or it can dispose of excess nitrogen as ammonia 
• In most mammals, toxic ammonia is quickly recaptured 
into carbamoyl phosphate and passed into the urea cycle
Sample question 
• The site of amino acid catabolism is the: 
A. Stomach 
B. Small intestine 
C. Large intestine 
D. Liver
Sample question 
• The first step in the catabolism of most amino 
acids is 
• A. Removal of carboxylate groups 
• B. Enzymatic hydrolysis of peptide bonds 
• C. Removal of the amino group 
• D. Zymogen cleavage
Sample question 
Which of the following is true of urea? 
• A. more toxic to human cells than ammonia 
• B. the primary nitrogenous waste products of 
humans. 
• C. insoluble in water 
• D. the primary nitrogenous waste product of 
most aquatic invertebrates
Sample question 
A glucogenic amino acid is one which is 
degraded to 
• A. keto-sugars 
• B. either acetyl CoA or acetoacetyl CoA 
• C. pyruvate or citric acid cycle 
intermediates 
• D. none of the above
Sample question 
Transamination is the process where 
• A. carboxyl group is transferred from amino 
acid 
• B. α-amino group is removed from the amino 
acid 
• C. polymerization of amino acid takes place 
• D. none of the above
Sample question 
Transamination is the transfer of an amino 
• A. acid to a carboxylic acid plus ammonia 
• B. group from an amino acid to a keto acid 
• C. acid to a keto acid plus ammonia 
• D. group from an amino acid to a carboxylic 
acid

More Related Content

What's hot

What's hot (20)

De novo and salvage pathway of purines
De novo and salvage pathway of purinesDe novo and salvage pathway of purines
De novo and salvage pathway of purines
 
Amino acid catabolism
Amino acid catabolismAmino acid catabolism
Amino acid catabolism
 
De novo and salvage pathway of nucleotides synthesis.pptx
De novo and salvage pathway of nucleotides synthesis.pptxDe novo and salvage pathway of nucleotides synthesis.pptx
De novo and salvage pathway of nucleotides synthesis.pptx
 
Purine and Pyrimidine biosynthesis
Purine and Pyrimidine biosynthesisPurine and Pyrimidine biosynthesis
Purine and Pyrimidine biosynthesis
 
Determination of primary structure of proteins
Determination of primary structure of proteinsDetermination of primary structure of proteins
Determination of primary structure of proteins
 
TCA Cycle
TCA CycleTCA Cycle
TCA Cycle
 
Biosynthesis of amino acid (essential and non essential)
Biosynthesis of amino acid (essential and non essential)Biosynthesis of amino acid (essential and non essential)
Biosynthesis of amino acid (essential and non essential)
 
Oxidation of fatty acids
Oxidation of fatty acidsOxidation of fatty acids
Oxidation of fatty acids
 
Amino acid metabolism
Amino acid metabolismAmino acid metabolism
Amino acid metabolism
 
High energy compounds
High energy compoundsHigh energy compounds
High energy compounds
 
Amino acids metabolism new
Amino acids metabolism newAmino acids metabolism new
Amino acids metabolism new
 
BIOSYNTHESIS OF FATTY ACIDS
BIOSYNTHESIS OF FATTY ACIDSBIOSYNTHESIS OF FATTY ACIDS
BIOSYNTHESIS OF FATTY ACIDS
 
Atp synthesis
Atp synthesisAtp synthesis
Atp synthesis
 
Pyrimidine Synthesis and Degradation
Pyrimidine Synthesis and DegradationPyrimidine Synthesis and Degradation
Pyrimidine Synthesis and Degradation
 
Metabolism of amino acids
Metabolism of amino acidsMetabolism of amino acids
Metabolism of amino acids
 
Biosynthesis of Purine Ribonucleotide, Gout
Biosynthesis of Purine Ribonucleotide, GoutBiosynthesis of Purine Ribonucleotide, Gout
Biosynthesis of Purine Ribonucleotide, Gout
 
Amino acid metabolism | Transamination | Deamination |
Amino acid metabolism | Transamination | Deamination |Amino acid metabolism | Transamination | Deamination |
Amino acid metabolism | Transamination | Deamination |
 
3.TRANSAMINATION.pptx
3.TRANSAMINATION.pptx3.TRANSAMINATION.pptx
3.TRANSAMINATION.pptx
 
Biosynthesis of Phospholipids
Biosynthesis of PhospholipidsBiosynthesis of Phospholipids
Biosynthesis of Phospholipids
 
PYRIMIDINE SYNTHESIS
PYRIMIDINE SYNTHESISPYRIMIDINE SYNTHESIS
PYRIMIDINE SYNTHESIS
 

Similar to Biochemistry _ amino acid oxidation

Lec12 ureacyc
Lec12 ureacycLec12 ureacyc
Lec12 ureacyc
dream10f
 

Similar to Biochemistry _ amino acid oxidation (20)

Metabolism of amino acid
Metabolism of amino acid Metabolism of amino acid
Metabolism of amino acid
 
Beta oxidation & protein catabolism
Beta oxidation & protein catabolismBeta oxidation & protein catabolism
Beta oxidation & protein catabolism
 
Nitrogen metabolism (metabolic fate of amino acid, catabolism of amino acid, ...
Nitrogen metabolism (metabolic fate of amino acid, catabolism of amino acid, ...Nitrogen metabolism (metabolic fate of amino acid, catabolism of amino acid, ...
Nitrogen metabolism (metabolic fate of amino acid, catabolism of amino acid, ...
 
Amino acid metabolism
Amino acid metabolismAmino acid metabolism
Amino acid metabolism
 
Chapters 18 - Amino acid Oxidation , production of urea Biochemistry
Chapters 18 - Amino acid Oxidation , production of urea Biochemistry Chapters 18 - Amino acid Oxidation , production of urea Biochemistry
Chapters 18 - Amino acid Oxidation , production of urea Biochemistry
 
Chapters 18 , 22 - Biochemistry
Chapters 18 , 22 - BiochemistryChapters 18 , 22 - Biochemistry
Chapters 18 , 22 - Biochemistry
 
Urea cycle.. lgis
Urea cycle.. lgisUrea cycle.. lgis
Urea cycle.. lgis
 
urea- tca cycle(0).pdf
urea- tca cycle(0).pdfurea- tca cycle(0).pdf
urea- tca cycle(0).pdf
 
AMINO ACID power presentation that describes amino acids
AMINO ACID power presentation that describes amino acidsAMINO ACID power presentation that describes amino acids
AMINO ACID power presentation that describes amino acids
 
image (1).pdf
image (1).pdfimage (1).pdf
image (1).pdf
 
Amino acid meatbolism and Urea cycle-1.pptx
Amino acid meatbolism and Urea cycle-1.pptxAmino acid meatbolism and Urea cycle-1.pptx
Amino acid meatbolism and Urea cycle-1.pptx
 
Amino acid meatbolism and urea cycle(1)
Amino acid meatbolism and urea cycle(1)Amino acid meatbolism and urea cycle(1)
Amino acid meatbolism and urea cycle(1)
 
Amino acid meatbolism and urea cycle
Amino acid meatbolism and urea cycleAmino acid meatbolism and urea cycle
Amino acid meatbolism and urea cycle
 
Unit 5.ppt
Unit 5.pptUnit 5.ppt
Unit 5.ppt
 
Catabolism of proteins and amino acids
Catabolism of proteins and amino acidsCatabolism of proteins and amino acids
Catabolism of proteins and amino acids
 
Lec12 ureacyc
Lec12 ureacycLec12 ureacyc
Lec12 ureacyc
 
Nitrogen Disposal
Nitrogen DisposalNitrogen Disposal
Nitrogen Disposal
 
Metabolism of Protein and Amino Acids
Metabolism of Protein and Amino AcidsMetabolism of Protein and Amino Acids
Metabolism of Protein and Amino Acids
 
Protein Metabolism .ppt
Protein Metabolism .pptProtein Metabolism .ppt
Protein Metabolism .ppt
 
Protein metabolism.ppt
Protein metabolism.pptProtein metabolism.ppt
Protein metabolism.ppt
 

More from Prabesh Raj Jamkatel

16 zoonoses [zoʊ'ɒnəsɪs] pathogens
16 zoonoses [zoʊ'ɒnəsɪs] pathogens16 zoonoses [zoʊ'ɒnəsɪs] pathogens
16 zoonoses [zoʊ'ɒnəsɪs] pathogens
Prabesh Raj Jamkatel
 
7 prevetion of pathogenic microbial infection
7 prevetion of  pathogenic microbial infection7 prevetion of  pathogenic microbial infection
7 prevetion of pathogenic microbial infection
Prabesh Raj Jamkatel
 

More from Prabesh Raj Jamkatel (20)

18 mycoplasm,chlmydia,rickettsia
18 mycoplasm,chlmydia,rickettsia18 mycoplasm,chlmydia,rickettsia
18 mycoplasm,chlmydia,rickettsia
 
17 spirochetes
17  spirochetes17  spirochetes
17 spirochetes
 
16 zoonoses pathogens
16 zoonoses pathogens16 zoonoses pathogens
16 zoonoses pathogens
 
16 zoonoses [zoʊ'ɒnəsɪs] pathogens
16 zoonoses [zoʊ'ɒnəsɪs] pathogens16 zoonoses [zoʊ'ɒnəsɪs] pathogens
16 zoonoses [zoʊ'ɒnəsɪs] pathogens
 
15 corynebacterium diphtheriae
15 corynebacterium diphtheriae15 corynebacterium diphtheriae
15 corynebacterium diphtheriae
 
14 mycobacteria
14 mycobacteria14 mycobacteria
14 mycobacteria
 
13 anaerobic bacteria
13 anaerobic bacteria13 anaerobic bacteria
13 anaerobic bacteria
 
12 campylobacter helicobacter
12 campylobacter helicobacter12 campylobacter helicobacter
12 campylobacter helicobacter
 
11 vibrios
11 vibrios11 vibrios
11 vibrios
 
10 enterobacteriaceae
10 enterobacteriaceae10 enterobacteriaceae
10 enterobacteriaceae
 
9 cocci
9 cocci9 cocci
9 cocci
 
8 drug resistance
8 drug resistance8 drug resistance
8 drug resistance
 
7 prevetion of pathogenic microbial infection
7 prevetion of  pathogenic microbial infection7 prevetion of  pathogenic microbial infection
7 prevetion of pathogenic microbial infection
 
6 laboratory diagnosis of bacterial infection
6 laboratory diagnosis  of bacterial infection6 laboratory diagnosis  of bacterial infection
6 laboratory diagnosis of bacterial infection
 
5 immune defense against bacterial pathogens
5 immune defense against bacterial  pathogens5 immune defense against bacterial  pathogens
5 immune defense against bacterial pathogens
 
4 bacterial infection and pathogenesis
4  bacterial infection and pathogenesis4  bacterial infection and pathogenesis
4 bacterial infection and pathogenesis
 
3 heredity and variation of bacteria
3 heredity and variation of bacteria3 heredity and variation of bacteria
3 heredity and variation of bacteria
 
2 biosafety
2 biosafety2 biosafety
2 biosafety
 
0 introdution to Medical Microbiology
0  introdution to Medical Microbiology0  introdution to Medical Microbiology
0 introdution to Medical Microbiology
 
1 basic characters of bacteria
1 basic characters of bacteria1 basic characters of bacteria
1 basic characters of bacteria
 

Recently uploaded

SPLICE Working Group: Reusable Code Examples
SPLICE Working Group:Reusable Code ExamplesSPLICE Working Group:Reusable Code Examples
SPLICE Working Group: Reusable Code Examples
Peter Brusilovsky
 
Orientation Canvas Course Presentation.pdf
Orientation Canvas Course Presentation.pdfOrientation Canvas Course Presentation.pdf
Orientation Canvas Course Presentation.pdf
Elizabeth Walsh
 

Recently uploaded (20)

What is 3 Way Matching Process in Odoo 17.pptx
What is 3 Way Matching Process in Odoo 17.pptxWhat is 3 Way Matching Process in Odoo 17.pptx
What is 3 Way Matching Process in Odoo 17.pptx
 
Pharmaceutical Biotechnology VI semester.pdf
Pharmaceutical Biotechnology VI semester.pdfPharmaceutical Biotechnology VI semester.pdf
Pharmaceutical Biotechnology VI semester.pdf
 
TỔNG HỢP HƠN 100 ĐỀ THI THỬ TỐT NGHIỆP THPT TOÁN 2024 - TỪ CÁC TRƯỜNG, TRƯỜNG...
TỔNG HỢP HƠN 100 ĐỀ THI THỬ TỐT NGHIỆP THPT TOÁN 2024 - TỪ CÁC TRƯỜNG, TRƯỜNG...TỔNG HỢP HƠN 100 ĐỀ THI THỬ TỐT NGHIỆP THPT TOÁN 2024 - TỪ CÁC TRƯỜNG, TRƯỜNG...
TỔNG HỢP HƠN 100 ĐỀ THI THỬ TỐT NGHIỆP THPT TOÁN 2024 - TỪ CÁC TRƯỜNG, TRƯỜNG...
 
SPLICE Working Group: Reusable Code Examples
SPLICE Working Group:Reusable Code ExamplesSPLICE Working Group:Reusable Code Examples
SPLICE Working Group: Reusable Code Examples
 
Orientation Canvas Course Presentation.pdf
Orientation Canvas Course Presentation.pdfOrientation Canvas Course Presentation.pdf
Orientation Canvas Course Presentation.pdf
 
Play hard learn harder: The Serious Business of Play
Play hard learn harder:  The Serious Business of PlayPlay hard learn harder:  The Serious Business of Play
Play hard learn harder: The Serious Business of Play
 
FICTIONAL SALESMAN/SALESMAN SNSW 2024.pdf
FICTIONAL SALESMAN/SALESMAN SNSW 2024.pdfFICTIONAL SALESMAN/SALESMAN SNSW 2024.pdf
FICTIONAL SALESMAN/SALESMAN SNSW 2024.pdf
 
Diuretic, Hypoglycemic and Limit test of Heavy metals and Arsenic.-1.pdf
Diuretic, Hypoglycemic and Limit test of Heavy metals and Arsenic.-1.pdfDiuretic, Hypoglycemic and Limit test of Heavy metals and Arsenic.-1.pdf
Diuretic, Hypoglycemic and Limit test of Heavy metals and Arsenic.-1.pdf
 
Including Mental Health Support in Project Delivery, 14 May.pdf
Including Mental Health Support in Project Delivery, 14 May.pdfIncluding Mental Health Support in Project Delivery, 14 May.pdf
Including Mental Health Support in Project Delivery, 14 May.pdf
 
8 Tips for Effective Working Capital Management
8 Tips for Effective Working Capital Management8 Tips for Effective Working Capital Management
8 Tips for Effective Working Capital Management
 
Graduate Outcomes Presentation Slides - English
Graduate Outcomes Presentation Slides - EnglishGraduate Outcomes Presentation Slides - English
Graduate Outcomes Presentation Slides - English
 
Andreas Schleicher presents at the launch of What does child empowerment mean...
Andreas Schleicher presents at the launch of What does child empowerment mean...Andreas Schleicher presents at the launch of What does child empowerment mean...
Andreas Schleicher presents at the launch of What does child empowerment mean...
 
Graduate Outcomes Presentation Slides - English (v3).pptx
Graduate Outcomes Presentation Slides - English (v3).pptxGraduate Outcomes Presentation Slides - English (v3).pptx
Graduate Outcomes Presentation Slides - English (v3).pptx
 
UGC NET Paper 1 Unit 7 DATA INTERPRETATION.pdf
UGC NET Paper 1 Unit 7 DATA INTERPRETATION.pdfUGC NET Paper 1 Unit 7 DATA INTERPRETATION.pdf
UGC NET Paper 1 Unit 7 DATA INTERPRETATION.pdf
 
OSCM Unit 2_Operations Processes & Systems
OSCM Unit 2_Operations Processes & SystemsOSCM Unit 2_Operations Processes & Systems
OSCM Unit 2_Operations Processes & Systems
 
HMCS Max Bernays Pre-Deployment Brief (May 2024).pptx
HMCS Max Bernays Pre-Deployment Brief (May 2024).pptxHMCS Max Bernays Pre-Deployment Brief (May 2024).pptx
HMCS Max Bernays Pre-Deployment Brief (May 2024).pptx
 
dusjagr & nano talk on open tools for agriculture research and learning
dusjagr & nano talk on open tools for agriculture research and learningdusjagr & nano talk on open tools for agriculture research and learning
dusjagr & nano talk on open tools for agriculture research and learning
 
HMCS Vancouver Pre-Deployment Brief - May 2024 (Web Version).pptx
HMCS Vancouver Pre-Deployment Brief - May 2024 (Web Version).pptxHMCS Vancouver Pre-Deployment Brief - May 2024 (Web Version).pptx
HMCS Vancouver Pre-Deployment Brief - May 2024 (Web Version).pptx
 
Michaelis Menten Equation and Estimation Of Vmax and Tmax.pptx
Michaelis Menten Equation and Estimation Of Vmax and Tmax.pptxMichaelis Menten Equation and Estimation Of Vmax and Tmax.pptx
Michaelis Menten Equation and Estimation Of Vmax and Tmax.pptx
 
VAMOS CUIDAR DO NOSSO PLANETA! .
VAMOS CUIDAR DO NOSSO PLANETA!                    .VAMOS CUIDAR DO NOSSO PLANETA!                    .
VAMOS CUIDAR DO NOSSO PLANETA! .
 

Biochemistry _ amino acid oxidation

  • 1. CHAPTER 19 Amino Acid Oxidation Production of Urea Key topics: – How proteins are digested in animals – How amino acids are degraded in animals – How urea is made and excreted
  • 2. Oxidation of Amino Acids is a Significant Energy-Yielding Pathway in Carnivores • Not all organisms use amino acids as the source of energy • About 90% of energy needs of carnivores can be met by amino acids immediately after a meal • Only a small fraction of energy needs of herbivores are met by amino acids • Microorganisms scavenge amino acids from their environment for fuel
  • 3. Sources and Uses of Amino Acids Sources 1.Proteins in the diet provide both essential and non-essential amino acids in contrast to microorganisms that for the most part synthesize their own. 2.Turnover of endogenous proteins 3.de novo biosynthesis (non-essential amino acids) Uses 1.Protein synthesis 2.Nitrogen and carbon source of general and special product biosynthesis 3.Energy source a.glucogenic (those that can be used for the synthesis of glucose) b.ketogenic (those whose metabolism leads to ketone bodies)
  • 4. Metabolic Circumstances of Amino Acid Oxidation Amino acids undergo oxidative catabolism under three circumstances: – Protein amino-acid residues from normal turnover are recycled to generate energy and molecular components – Dietary amino acids that exceed body’s protein synthesis needs are degraded – Proteins in the body are broken down to supply amino acids for catabolism when carbohydrates are in short supply (starvation, diabetes mellitus),
  • 5. Protein Turnover and Nitrogen Balance Protein Degradation: • Endogenous proteins degrade continuously - Damaged - Mis-folded - Un-needed • Dietary protein intake - mostly degraded Nitrogen Balance - expresses the patient’s current status - are they gaining or losing net Nitrogen?
  • 6. Dietary Proteins are Enzymatically Hydrolyzed • Pepsin cuts protein into peptides in the stomach • Trypsin and chymotrypsin cut proteins and larger peptides into smaller peptides in the small intestine • Aminopeptidase and carboxypeptidases A and B degrade peptides into amino acids in the small intestine
  • 7. stomach pancreas to small intestine intestinal wall pepsin Trypsin Chymotrypsin carboxypeptidase A carboxypeptidase B elastase dipeptidases
  • 8. Enzymatic Degradation of Dietary Proteins • (a) gastrin -> secretion of HCl by parietal cells and pepsin by chief cells • (b) exocrine cells synthesize zymogens – zymogen granules fuse with plasma membrane – zymogens released into the lumen of the collecting duct – collecting ducts -> pancreatic duct -> small intestine. • (c) Amino acids -> villi -> capillaries
  • 9. Overview of Amino Acid Catabolism
  • 10. OVERVIEW OF AMINO ACID METABOLISM ENVIRONMENT ORGANISM Ingested protein Bio-synthesis Protein 1 2 3 AMINO ACIDS Nitrogen Carbon skeletons Urea Degradation (required) a b Purines Pyrimidines Porphyrins c c (ketogenic) (glucogenic) Used for energy pyruvate α-ketoglutarate succinyl-CoA fumarate oxaloacetate acetoacetate acetyl CoA
  • 11. Degradation of amino acids to one of seven common metabolic intermediates.
  • 12. Amino acid metabolism • Metabolism of amino acids differs, but 3 common reactions: – Transamination – Deamination – Formation of urea
  • 13. Typical first transamination reaction: The usual AA acceptor is α-ketoglutarate, producing GLUTAMATE and the new a-keto acid. Transamination is a reaction between an amino acid and a keto-acid in which the amino group is transferred from the donor amino acid onto the acceptor keto-acid.
  • 15. Enzymatic Transamination • Typically, a-ketoglutarate accepts amino groups • L-Glutamine acts as a temporary storage of nitrogen • L-Glutamine can donate the amino group when needed for amino acid biosynthesis • All aminotransferases rely on the pyridoxal phosphate (PLP) cofactor
  • 16. Structure of Pyridoxal Phosphate and Pyridoxamine Phosphate • Intermediate, enzyme-bound carrier of amino groups • Aldehyde form can react reversibly with amino groups • Aminated form can react reversibly with carbonyl groups
  • 17. A small number of amino acids undergo oxidative or non-oxidative deamination
  • 18. 18 Urea Formation • Occurs primarily in liver; excreted by kidney • Principal method for removing ammonia • Hyperammonemia: • Defects in urea cycle enzymes • Severe neurological defects in neonates
  • 19. Treatment of deficiency of Urea Cycle enzymes (depends on which enzyme is deficient):  limiting protein intake to the amount barely adequate to supply amino acids for growth, while adding to the diet the a-keto acid analogs of essential amino acids.  Liver transplantation has also been used, since liver is the organ that carries out Urea Cycle.  Dialysis  Increase ammonia excretion: Na benzoate, Na phenylbutyrate, L-arginine, L-citrulline
  • 20. Postulated mechanisms for toxicity of high [ammonia]: 1. High [NH3] would drive Glutamine Synthase: glutamate + ATP + NH3  glutamine + ADP + Pi This would deplete glutamate – a neurotransmitter & precursor for synthesis of the neurotransmitter GABA. 2. Depletion of glutamate & high ammonia level would drive Glutamate Dehydrogenase reaction to reverse: glutamate + NAD(P)+ a-ketoglutarate + NAD(P)H + NH4 + The resulting depletion of a-ketoglutarate, an essential Krebs Cycle intermediate, could impair energy metabolism in the brain.
  • 21. 21 GABA Formation NH3 + -O2CCH2CH2CHCO2 - NH3 + -O2CCH2CH2CH2 Glutamate decarboxylase Glutamate Gamma-aminobutyrate (GABA) CO2 GABA is an important inhibitory neurotransmitter in the brain Drugs (e.g., benzodiazepines) that enhance the effects of GABA are useful in treating epilepsy
  • 22. • Glutamate is the precursor of free GABA in GABAergic terminals and comes from two different sources (Kreb's cycle in glia cells and glutamine in nerve terminals). Next, the enzyme glutamic acid decarboxylase (GAD) forms GABA from glutamate. After being released into the synapses, GABA is inactivated by reuptake mediated by GABA transporters (GATs) into presynaptic terminals or into glia cells where it is metabolized by GABA-transaminase (GABA-T).
  • 23. NN bbaallaannccee == NNiinn -- NNoouutt 1 Major dietary source of N is Protein (>95%), since the diet has very few free amino acids (AA) 2 AA are used for Protein Synthesis & N containing compounds 3 AA in excess are degraded (used for energy) N is disposed of in urea (80%), ammonia, uric acid or creatinine in urine with small amounts in fecal matter (undigested)
  • 24. Nitrogen Acquisition • Nitrogen Fixation • Nitrate Assimilation • Ammonium Assimilation
  • 25. N2 is converted to metabolically useful forms (is "fixed") only by a few species of prokaryotes, called Diazotrophs. Diazotrophs of the genus Rhizobium live symbiotically in the root nodules of legumes, where they convert N2 to NH3 (ammonia) in a process called NITROGEN FIXATION: NITROGENASE N2 + 8 H+ + 8 e- + 16 ATP + 16 H2O → 2 NH3 + H2 + 16 ADP + 16 Pi
  • 26. * But, less than 1% of N entering the biosphere comes from N fixation. Another oxidized form of nitrogen, NO3 - (nitrate ion) is also found in the soils and oceans. It is converted to NH4 + through NITRATE ASSIMILATION: * The reduction of NO3 - to NH4 + (ammonium ion) occurs in green plants, various fungi, and certain bacteria in a two-step p(1a) tThhew 2a-eyl:ectron reduction of nitrate to nitrite: NO3 - + 2 H+ + 2 e- → NO2 - + H2O ( catalyzed by nitrate reductase) (2) This is followed by the 6-electron reduction of nitrite to ammonium: NO2 - + 8 H+ + 6 e- → NH4 + + 2 H2O ( catalyzed by nitrite reductase) *NH3/NH4 + can be incorporated into the amino acids glutamate by glutamate dehydrogenase (and glutamine by glutamine synthetase.
  • 27. Nitrate Assimilation (Green plants, some fungi and bacteria) NO3 – + NADH + H+ NO2 – + H2O + NAD+ Nitrate Reductase NO2 – + 8H+ + 6e– NH4 + + 2H2O Nitrite Reductase
  • 28. Ammonium Assimilation (Carbamoyl Phosphate Synthetase) O H2N C OP 2ATP 2ADP+Pi – NH3 + HCO3 (Biosynthetic Glutamate Dehydrogenase) and/or (Glutamine Synthetase) NH3 Glutamate NH3 Glutamine
  • 29. No animals are capable of either N-fixation or nitrate assimilation, so animals are totally dependent on plants and microorganisms for the synthesis of organic nitrogenous compounds, such as amino acids and proteins, to provide this essential nutrient.
  • 30. Nitrogen balance • Protein content of adult body remains remarkably constant – Protein constitutes 10-15% of diet • Equivalent amount of amino acids must be lost each day Nitrogen balance = nitrogen ingested - nitrogen excreted (primarily as protein) (primarily as urea) Nitrogen balance = 0 (nitrogen equilibrium) protein synthesis = protein degradation Positive nitrogen balance protein synthesis > protein degradation Negative nitrogen balance protein synthesis < protein degradation
  • 31. Fates of Nitrogen in Organisms • Plants conserve almost all the nitrogen • Many aquatic vertebrates release ammonia to their environment – Passive diffusion from epithelial cells – Active transport via gills • Many terrestrial vertebrates and sharks excrete nitrogen in the form of urea – Urea is far less toxic that ammonia – Urea has very high solubility • Some animals, such as birds and reptiles excrete nitrogen as uric acid – Uric acid is rather insoluble – Excretion as paste allows to conserve water • Humans and great apes excrete both urea (from amino acids) and uric acid (from purines)
  • 32. Excretory Forms of Nitrogen
  • 33. The Amino Group is Removed From All Amino Acids First
  • 34. Glutamate can Donate Ammonia to Pyruvate to Make Alanine • Vigorously working muscles operate nearly anaerobically and rely on glycolysis for energy • Glycolysis yields pyruvate that muscles cannot metabolize aerobically; if not eliminated lactic acid will build up • This pyruvate can be converted to alanine for transport into liver
  • 35. Ammonia in Transported in the Bloodstream Safely as Glutamate • Un-needed glutamine is processed in intestines, kidneys and liver
  • 36. Excess Glutamate is Metabolized in the Mitochondria of Hepatocytes
  • 37. The Glutamate Dehydrogenase Reaction • Two-electron oxidation of glutamate followed by hydrolysis • Net process is oxidative deamination of glutamate • Occurs in mitochondrial matrix in mammals • Can use either NAD+ or NADP+ as electron acceptor
  • 38. Nitrogen from Carbamoyl Phosphate Enters the Urea Cycle
  • 39. Urea Cycle • UUrreeaa iiss pprroodduucceedd iinn tthhee lliivveerr • FFrroomm tthhee lliivveerr,, iitt iiss ttrraannssppoorrtteedd iinn tthhee bblloooodd ttoo tthhee kkiiddnneeyyss ffoorr eexxccrreettiioonn iinn uurriinnee UUrreeaa iiss ccoommppoosseedd ooff:: TTwwoo nniittrrooggeenn aattoommss • First nitrogen atom is from ffrreeee aammmmoonniiaa • Second nitrogen atom is from aassppaarrttaattee CCaarrbboonn && ooxxyyggeenn aattoommss aarree ffrroomm CCOO22
  • 40. The Reactions in the Urea Cycle • 1 ornithine + carbamoyl phosphate => citrulline – (entry of the first amino group). – citrulline passes into the cytosol. • 2a citrulline + ATP => citrullyl-AMP + PPi • 2b citrullyl-AMP + Aspartate => argininosuccinate + AMP – (entry of the second amino group). • 3 argininosuccinate => arginine + fumarate – fumarate enters the citric acid cycle. • 4 arginine => urea + ornithine – Ornithine passes to the mitochondria to continue the cycle
  • 41. Urea Cycle N-2 from Aspartate
  • 42. Ammonia is Re-captured via Synthesis of Carbamoyl Phosphate • This is the first nitrogen-acquiring reaction
  • 43. Entry of Aspartate into the Urea Cycle • This is the second nitrogen-acquiring reaction
  • 44. Aspartate –Argininosuccinate Shunt Links Urea Cycle and Citric Acid Cycle
  • 45. 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.
  • 46. FFaattee ooff UUrreeaa UUrreeaa ((ssyynntthheessiizzeedd iinn tthhee lliivveerr)) BBlloooodd KKiiddnneeyy intestine Urine cleaved by bacterial urease AAmmmmoonniiaa CO2 In stool Reabsorbed in blood
  • 47.
  • 48. Disposal of Ammonia 1- UUrreeaa iinn tthhee lliivveerr • is quantitatively the mmoosstt iimmppoorrttaanntt disposal route for ammonia • Urea is formed in the lliivveerr from ammonia (urea cycle) • UUrreeaa travels in the blood from the liver to the kkiiddnneeyyss where it is filtered to appear in uurriinnee
  • 49. Disposal of Ammonia 2- GGlluuttaammiinnee iinn mmoosstt ppeerriipphheerraall ttiissssuueess eessppeecciiaallllyy bbrraaiinn,, SSkkeelleettaall MMuusscclleess && lliivveerr • In most peripheral tissues, glutamate binds with aammmmoonniiaa by action of gglluuttaammiinnee ssyynntthhaassee • in the bbrraaiinn, it is the major mechanism of removal of ammonia from the brain • This structure provides a nnoonnttooxxiicc ssttoorraaggee && ttrraannssppoorrtt ffoorrmm ooff aammmmoonniiaa • Glutamine is transported to blood to other organs esp. liver & kidneys • In the liver & Kidney, glutamine is converted to ammonia & glutamate by the enzyme gglluuttaammiinnaassee.
  • 50. Disposal of Ammonia 3- AAllaanniinnee iinn sskkeelleettaall mmuusscclleess • AAmmmmoonniiaa + Pyruvate form aallaanniinnee in skeletal muscles • Alanine is transported in blood to liver • In liver, alanine is converted to pyruvate & aammmmoonniiaa • Pyruvate can be converted to gglluuccoossee (by gluconeogenesis) • GGlluuccoossee can enter the blood to be used by skeletal muscles ((GGLLUUCCOOSSEE -- AALLAANNIINNEE PPAATTHHWWAAYY))
  • 51. Disposal of Ammonia GGlluuttaammiinnee iinn MMoosstt TTiissssuueess EEsspp.. bbrraaiinn && KKiiddnneeyyss UUrreeaa iinn LLiivveerr AAllaanniinnee iinn SSkkeelleettaall MMuusscclleess
  • 52. Not All Amino Acids can be Synthesized in Humans • These amino acids must be obtained as dietary protein • Consumption of a variety of foods (including vegetarian only diets) well supplies all the essential amino acids
  • 53. Essential amino acids Mammalian cells lack enzymes to synthesize their carbon skeletons (a-keto acids). Isoleucine, leucine, & valine Lysine Threonine Tryptophan Phenylalanine (Tyr can be made from Phe.) Methionine (Cys can be made from Met.) Histidine (Essential for infants.)
  • 54. 54 •One way to remember the 9 essential amino acids is with the mnemonic VF WITH MLK (Very Full With Milk): V Valine F Phenylalanine W Tryptophan I Isoleucine T Threonine H Histidine M Methionine L Leucine K Lysine
  • 55. Fates of carbon skeleton of amino acids
  • 56. Fate of Individual Amino Acids • Seven to acetyl-CoA – Leu, Ile, Thr, Lys, Phe, Tyr, Trp • Six to pyruvate – Ala, Cys, Gly, Ser, Thr, Trp • Five to a-ketoglutarate – Arg, Glu, Gln, His, Pro • Four to succinyl-CoA – Ile, Met, Thr, Val • Two to fumarate – Phe, Tyr • Two to oxaloacetate – Asp, Asn
  • 57. Glucogenic vs ketogenic amino acids • Glucogenic amino acids (are degraded to pyruvate or citric acid cycle intermediates) - can supply gluconeogenesis pathway • Ketogenic amino acids (are degraded to acetyl CoA or acetoacetyl CoA) - can contribute to synthesis of fatty acids or ketone bodies • Some amino acids are both glucogenic and ketogenic
  • 58. Summary of Amino Acid Catabolism
  • 59. 6 Amino Acids -> Pyruvate Ala, Gly, Ser, Cys,Trp,Thr.
  • 60. 7 AAs -> Acetyl CoA [W,K,F,Y, L]
  • 61. I, M, T, V-> Succinyl-CoA
  • 62. Albinism – genetically determined lack or deficit of enzyme tyrosinase Tyrosinase in melanocytes oxidases tyrosine to DOPA and DOPA-chinone tyrosinase Phenylalanine Tyrosine Tyroxine Melanin DOPA Dopamine Norepinephrine Epinephrine
  • 63. The pathways for the biosynthesis of amino acids are diverse Common feature: carbon skeletons come from intermediates of  glycolysis,  pentose phosphate pathway,  citric acid cycle. All amino acids are grouped into families according to the intermediates that they are made from
  • 64.
  • 65. Summary • Amino acids from protein are an important energy source in carnivorous animals • Catabolism of amino acids involves transfer of the amino group via PLP-dependent aminotransferase to a donor such as a-ketoglutarate to yield L-glutamine • L-glutamine can be used to synthesize new amino acids, or it can dispose of excess nitrogen as ammonia • In most mammals, toxic ammonia is quickly recaptured into carbamoyl phosphate and passed into the urea cycle
  • 66. Sample question • The site of amino acid catabolism is the: A. Stomach B. Small intestine C. Large intestine D. Liver
  • 67. Sample question • The first step in the catabolism of most amino acids is • A. Removal of carboxylate groups • B. Enzymatic hydrolysis of peptide bonds • C. Removal of the amino group • D. Zymogen cleavage
  • 68. Sample question Which of the following is true of urea? • A. more toxic to human cells than ammonia • B. the primary nitrogenous waste products of humans. • C. insoluble in water • D. the primary nitrogenous waste product of most aquatic invertebrates
  • 69. Sample question A glucogenic amino acid is one which is degraded to • A. keto-sugars • B. either acetyl CoA or acetoacetyl CoA • C. pyruvate or citric acid cycle intermediates • D. none of the above
  • 70. Sample question Transamination is the process where • A. carboxyl group is transferred from amino acid • B. α-amino group is removed from the amino acid • C. polymerization of amino acid takes place • D. none of the above
  • 71. Sample question Transamination is the transfer of an amino • A. acid to a carboxylic acid plus ammonia • B. group from an amino acid to a keto acid • C. acid to a keto acid plus ammonia • D. group from an amino acid to a carboxylic acid

Editor's Notes

  1. Part of the human digestive (gastrointestinal) tract. (a) The parietal cells and chief cells of the gastric glands secrete their products in response to the hormone gastrin. Pepsin begins the process of protein degradation in the stomach. (b) The cytoplasm of exocrine cells is completely filled with rough endoplasmic reticulum, the site of synthesis of the zymogens of many digestive enzymes. The zymogens are concentrated in membrane-enclosed transport particles called zymogen granules. When an exocrine cell is stimulated, its plasma membrane fuses with the zymogen granule membrane and zymogens are released into the lumen of the collecting duct by exocytosis. The collecting ducts ultimately lead to the pancreatic duct and thence to the small intestine. (c) Amino acids are absorbed through the epithelial cell layer (intestinal mucosa) of the villi and enter the capillaries. Recall that the products of lipid hydrolysis in the small intestine enter the lymphatic system after their absorption by the intestinal mucosa.
  2. Urea cycle and reactions that feed amino groups into the cycle. The enzymes catalyzing these reactions are distributed between the mitochondrial matrix and the cytosol. One amino group enters the urea cycle as carbamoyl phosphate, formed in the matrix; the other enters as aspartate, formed in the matrix by transamination of oxaloacetate and glutamate, catalyzed by aspartate aminotransferase. The urea cycle consists of four steps. 1 Formation of citrulline from ornithine and carbamoyl phosphate (entry of the first amino group); the citrulline passes into the cytosol. 2 Formation of argininosuccinate through a citrullyl-AMP intermediate (entry of the second amino group). 3 Formation of arginine from argininosuccinate; this reaction releases fumarate, which enters the citric acid cycle. 4 Formation of urea; this reaction also regenerates ornithine.
  3. Links between the urea cycle and citric acid cycle. The interconnected cycles have been called the &amp;quot;Krebs bicycle.&amp;quot; The pathways linking the citric acid and urea cycles are known as the aspartate-argininosuccinate shunt; these effectively link the fates of the amino groups and the carbon skeletons of amino acids. The interconnections are even more elaborate than the arrows suggest. For example, some citric acid cycle enzymes, such as fumarase and malate dehydrogenase, have both cytosolic and mitochondrial isozymes. Fumarate produced in the cytosol—whether by the urea cycle, purine biosynthesis, or other processes—can be converted to cytosolic malate, which is used in the cytosol or transported into mitochondria (via the malate aspartate shuttle) to enter the citric acid cycle.
  4. Summary of amino acid catabolism. Amino acids are grouped according to their major degradative end product. Some amino acids are listed more than once because different parts of their carbon skeletons are degraded to different end products. The figure shows the most important catabolic pathways in vertebrates, but there are minor variations among vertebrate species. Threonine, for instance, is degraded via at least two different pathways, and the importance of a given pathway can vary with the organism and its metabolic conditions. The glucogenic and ketogenic amino acids are also delineated in the figure, by color shading. Notice that five of the amino acids are both glucogenic and ketogenic. The amino acids degraded to pyruvate are also potentially ketogenic. Only two amino acids, leucine and lysine, are exclusively ketogenic.
  5. Catabolic pathways for alanine, glycine, serine, cysteine, tryptophan, and threonine. The pathway for threonine degradation shown here accounts for only about a third of threonine catabolism. Several pathways for cysteine degradation lead to pyruvate. The sulfur of cysteine has several alternative fates. Carbon atoms here and in subsequent figures are color-coded as necessary to trace their fates.
  6. Catabolic pathways for tryptophan, lysine, phenylalanine, tyrosine, leucine, and isoleucine. These amino acids donate some of their carbons (red) to acetyl-CoA. Tryptophan, phenylalanine, tyrosine, and isoleucine also contribute carbons (blue) to pyruvate or citric acid cycle intermediates. The fate of nitrogen atoms is not traced in this scheme; in most cases they are transferred to α-ketoglutarate to form glutamate.
  7. Catabolic pathways for methionine, isoleucine, threonine, and valine. These amino acids are converted to succinyl-CoA; isoleucine also contributes two of its carbon atoms to acetyl-CoA. The pathway of threonine degradation shown here occurs in humans.