Protein and Amino Acid Metabolism
Protein and Amino Acid Metabolism
Protein and Amino Acid Metabolism
Metabolism
Example
Overall Reaction
Amino Acid Keto acid + NH3
Enzymes involved
1. Glutamate dehydrogenase
COOH H 2O
COOH COOH
(CH2)2 + NAD+ (CH2)2 (CH2)2
CH-COOH NH=C-COOH O=C-COOH
NH2
-Iminoglutaric -Ketoglutarate
acid + NH4 + NADH2
Glutamate
Oxidative Deamination (continued)
NH O
Imino acid Keto acid
Regeneration
FP. H2 + O2 FP + H2O2
NH2 NH2 NH
Imino acid
Serine Intermediate
±H2O
NH3 + CH3 -C-COOH
O
Pyruvic acid
Non-Oxidative Deamination (continued)
2. Amino acid desulfhydrases
Requires B6PO4 as cofactor
Sulfur-containing amino acids (cysteine,
homocysteine)
-H2S
S-CH2-CH-COOH CH2=C-COOH CH3-C-COOH
NH2 NH2 NH
Cysteine Imino acid
O
Pyruvic acid
Ways of Detoxifying Ammonia
2. Glutamine formation
Glutamine
Glutamic acid + NH3 Glutamine
Synthetase
3. Urea formation
4. Asparagine formation
Aspartic acid + NH3 Asparagine
Urea Cycle
Enzymes
1. Carbamoyl PO4
Synthetase
2. Ornithine
Transcarbamoylase
3. Argininosuccinate
synthetase
4. Argininosuccinase
5. Arginase
UREA CYCLE
Urea – major disposal form of amino
groups from amino acids.
- accounts for 90% of N-ctg.
components of urine.
- produced in the liver; excreted in
the urine.
UREA CYCLE
Sources of Nitrogen of Urea:
1. free NH3 2. Aspartate
1. Synthetic pathway
-Ketoacid + NH3 -amino acid
2. Glucogenic pathway
3. Ketogenic pathway
4. Miscellaneous pathways
O2 NH3
Metabolic Pathways for Glycine
Heme synthesis
Synthesis of purines forms positions 4, 5, 7 of
the purine ring
Constituent of glutathione
Conjugates with cholic acid to form glycocholic
acid
Conjugates with benzoic acid to form hippuric
acid
Synthesis of creatine
Two Principal Catabolic Pathways of
Cysteine
1. Direct oxidative pathway-
Cysteine sulfinate pathway
2. Transamination pathway-
3-Mercaptopyruvate pathway
1. Cystinuria (Cystine-Lysinuria)
Considered to be due to a renal transport
defect affecting renal reabsorptive
mechanisms for 4 amino acids – cystine,
lysine, arginine and ornithine
Manifested by increased urinary excretion of
cystine, lysine, arginine and ornithine
Cystine is insoluble may precipitate in
kidney tubules and form cystine calculi
Inborn Errors (continued)
Aldehyde DH
Acetaldehyde Acetyl CoA
Enzymes
1. Phenylalanine
monooxygenase
or phenylalanine
oxidase
or phenylalanine
hydroxylase
2. Homogentisate
1,2-dioxygenase
3. Tyrosinase
AAs converted to Succinyl CoA
1. Methionine
2. Valine & Ile
3. Threonine alpha-ketobutyrate
propionyl CoA succinyl CoA or to
pyruvate
AAs converted to succinyl CoA
Methionine
Inborn Errors
1. Homocystinuria
Deficiency to
cystathionine
synthetase
2. Cystathioninuria
Deficiency to
cystathionase
-KG
Transamination
Glu
-Ketoisovaleric acid
CoA, NAD+
-Ketoisovaleric acid
dehyrogenase NADH, CO2
Isobutyryl CoA
Acyl CoA DH
Methylacrylyl CoA
Propionyl CoA
Succinyl CoA
HMG-CoA
obligatory intermediate in cholesterol
biosynthesis and ketogenesis
-Methylacetoacetyl CoA
Propionyl CoA
Methylmalonyl CoA
Succinyl CoA
AAs converted to Acetyl CoA or
Acetoacetyl CoA
1. Leucine
2. Ile
3. Lys Alpha-aminoadipate-semialdehyde
Acetoacetyl CoA
4. Tryptophan
Leucine -KG
Transaminase
Glu
-Ketoisocaproic acid
CoA, NAD+
-Ketoisocaproic
dehyrogenase NADH, CO2
Isovaleryl CoA
Acyl CoA DH
ß-Methylcrotonyl CoA
ß-Hydroxy-ß-methyl
Glutaryl CoA (HMG-CoA)
-Aminoadipic acid
-Ketoadipic acid
Glutaryl CoA
Crotonyl CoA
Acetoacetyl CoA
Glucose – Alanine Cycle
Functions of Glucose – Alanine Cycle
Tissue
Protein
Nitrogen Balance