B.Sc. Zoology — Biochemistry & Molecular Biology
Catabolism of Amino Acids:
Transamination and Deamination
Level: Undergraduate University & Competitive Examinations
Key Topics: Amino Acid Catabolism • Transamination • Deamination • PLP • Urea Cycle
Prepared by: Dr Bhabesh Nath, Assistant Professor, Department of Zoology
B N College (A) Dhubri
1. Introduction
▶ 1.1 Definition of Amino Acid Catabolism
Amino acid catabolism refers to the metabolic processes by which amino acids are broken down (degraded) in living organisms to yield energy, carbon skeletons for biosynthesis, and nitrogenous waste products. Unlike carbohydrates and fats, the body does not have a dedicated storage form for amino acids. Therefore, excess amino acids — particularly those derived from dietary protein digestion or from the normal turnover of cellular proteins — must be either converted into other useful molecules or completely oxidized to release energy.
The catabolism of amino acids is not a single pathway but rather a complex network of reactions. All 20 standard amino acids, despite their diverse chemical structures, share a common initial fate: the removal of the amino group (–NH₂). The remaining carbon skeleton, called the α-keto acid, then enters one of several central metabolic pathways such as the citric acid cycle (Krebs cycle), gluconeogenesis, or ketogenesis.
▶ 1.2 Importance of Amino Acid Breakdown in Metabolism
The catabolism of amino acids serves several crucial physiological roles:
• Energy Production: During prolonged starvation, intense exercise, or low-carbohydrate states, amino acids serve as an important fuel source. Their carbon skeletons are fed into the citric acid cycle to produce ATP.
• Nitrogen Excretion: Animals must excrete the nitrogen released from amino acids. In mammals, this nitrogen is converted to urea via the urea cycle — a critical detoxification process.
• Gluconeogenesis and Ketogenesis: Many amino acids contribute carbon skeletons that are used to synthesize glucose (glucogenic amino acids) or ketone bodies (ketogenic amino acids), or both — helping maintain blood glucose levels.
• Biosynthesis of Other Molecules: Degradation intermediates serve as precursors for nucleotides, porphyrins, neurotransmitters, and other vital biomolecules.
• Protein Turnover: The continuous breakdown and re-synthesis of proteins allows cells to remove damaged or misfolded proteins and respond to changing metabolic demands.
2. Overview of Amino Acid Catabolism
Amino acid catabolism can be broadly divided into two major stages:
Two Stages of Amino Acid Catabolism |
Stage 1 — Removal of the α-Amino Group: The amino group is removed from the α-carbon by transamination and/or deamination and is eventually converted to ammonia (NH₃) and then to urea for excretion. |
Stage 2 — Fate of the Carbon Skeleton (α-Keto Acid): The resulting carbon skeleton (α-keto acid) is degraded into one of seven metabolic intermediates: pyruvate, acetyl-CoA, acetoacetyl-CoA, α-ketoglutarate, succinyl-CoA, fumarate, or oxaloacetate — all of which feed into the citric acid cycle. |
2.1 Removal of the Amino Group
The first step in catabolism is almost always the transfer or removal of the α-amino group. Two key reactions accomplish this:
• Transamination: The amino group is transferred to α-ketoglutarate, forming glutamate. This is the most common initial reaction for most amino acids.
• Oxidative Deamination: Glutamate undergoes oxidative deamination by glutamate dehydrogenase to release free ammonia (NH₃) and regenerate α-ketoglutarate.
• Other Deamination Types: Some amino acids undergo non-oxidative or hydrolytic deamination (e.g., serine, threonine, asparagine, glutamine).
2.2 Fate of the Carbon Skeleton
After nitrogen removal, the resulting α-keto acids enter central metabolic pathways. Based on their metabolic fate, amino acids are classified into two broad categories:
Classification | Definition | Examples of Amino Acids | End Products |
Glucogenic Amino Acids | Their carbon skeletons yield pyruvate or citric acid cycle intermediates that can be converted to glucose | Alanine, Aspartate, Glutamate, Methionine, Valine | Pyruvate, OAA, α-KG, Fumarate, Succinyl-CoA → Glucose |
Ketogenic Amino Acids | Their catabolism produces acetyl-CoA or acetoacetyl-CoA, which cannot be used to synthesize glucose but form ketone bodies | Leucine, Lysine | Acetyl-CoA, Acetoacetyl-CoA → Ketone bodies |
Both Glucogenic & Ketogenic | Their carbon skeletons can yield both gluconeogenic and ketogenic products | Isoleucine, Phenylalanine, Tyrosine, Tryptophan, Threonine | Both glucose and ketone bodies |
3. Transamination
3.1 Definition
Transamination (also called aminotransfer) is a reversible biochemical reaction in which the α-amino group of an amino acid is transferred to the keto group of an α-keto acid, typically α-ketoglutarate (2-oxoglutarate). This reaction produces a new amino acid and a new α-keto acid (corresponding to the original amino acid), without any free ammonia being released.
Key Point to Remember |
Transamination does NOT release free ammonia. It is merely a transfer of the amino group from one molecule to another. The amino group is ultimately channelled to glutamate, from where it is released as ammonia by a separate deamination reaction. |
3.2 General Reaction of Transamination
The general equation for transamination is:
Amino acid₁ + α-Ketoglutarate ⇌ α-Keto acid₁ + L-Glutamate
In this reaction, the α-amino group of amino acid₁ is transferred to α-ketoglutarate, producing L-glutamate, while amino acid₁ becomes its corresponding α-keto acid. This reaction is catalysed by enzymes called aminotransferases (transaminases), which require pyridoxal phosphate (PLP) as a coenzyme.
3.3 Mechanism of Transamination
The mechanism of transamination is a two-stage (ping-pong) reaction, also known as the double-displacement mechanism, involving the coenzyme pyridoxal phosphate (PLP). The following steps outline the mechanism:
Step 1: Formation of Schiff Base (External Aldimine)
PLP is initially covalently bound to the enzyme (specifically to the ε-amino group of a lysine residue at the active site) via a Schiff base linkage (internal aldimine). When the amino acid substrate enters, it displaces the lysine and forms an external aldimine with PLP — a new Schiff base between the amino group of the substrate amino acid and the aldehyde group of PLP.
Step 2: Tautomeric Shift — Formation of Ketimine
The external aldimine undergoes a tautomeric shift (proton shift from the α-carbon to the nitrogen of PLP). This produces a ketimine intermediate, which upon hydrolysis yields pyridoxamine phosphate (PMP) and the corresponding α-keto acid (derived from the original amino acid).
Step 3: Reaction with α-Ketoglutarate
The PMP (which now carries the amino group) reacts with α-ketoglutarate in the reverse sequence: PMP condenses with α-ketoglutarate to form a ketimine, which rearranges to an aldimine, which then hydrolyses to release L-glutamate and regenerate PLP. The enzyme is now ready for another round of catalysis.
Summary of the Two Half-Reactions |
Half-Reaction 1 (Reductive Amination of PLP): Amino Acid + PLP-Enzyme → α-Keto Acid + PMP-Enzyme |
Half-Reaction 2 (Transamination to α-Ketoglutarate): PMP-Enzyme + α-Ketoglutarate → PLP-Enzyme + L-Glutamate |
Overall: Amino Acid + α-Ketoglutarate ⇌ α-Keto Acid + L-Glutamate |
3.4 Role of Aminotransferase (Transaminase) Enzymes
Aminotransferases are a large family of enzymes that catalyse transamination reactions. Each aminotransferase is specific for a particular amino acid–keto acid pair. However, almost all of them use α-ketoglutarate as the amino group acceptor and L-glutamate as the amino group donor. The two most physiologically significant and clinically important aminotransferases are:
Property | Alanine Aminotransferase (ALT) | Aspartate Aminotransferase (AST) |
Also known as | Glutamate Pyruvate Transaminase (GPT) | Glutamate Oxaloacetate Transaminase (GOT) |
Reaction catalysed | L-Alanine + α-Ketoglutarate ⇌ Pyruvate + L-Glutamate | L-Aspartate + α-Ketoglutarate ⇌ Oxaloacetate + L-Glutamate |
Primary location | Liver (most abundant); also in kidney | Liver, heart, skeletal muscle, kidney, red blood cells |
Coenzyme required | Pyridoxal Phosphate (PLP) | Pyridoxal Phosphate (PLP) |
Clinical significance | Most specific marker for liver cell damage | Elevated in liver disease and heart attack (myocardial infarction) |
3.5 Importance of Pyridoxal Phosphate (PLP)
Pyridoxal phosphate (PLP) is the active, phosphorylated form of Vitamin B₆ (pyridoxine). It is an indispensable coenzyme for aminotransferase enzymes and indeed for the vast majority of reactions involving amino acids. Understanding its role is critical:
Structure of PLP
PLP is a derivative of pyridine (a six-membered aromatic ring with nitrogen). It contains a hydroxymethyl group, a formyl group (aldehyde group, –CHO), a methyl group, and a phosphate group. The key functional component is the aldehyde group, which forms the Schiff base linkage with amino acids.
Functions of PLP in Transamination
• Electrophilic Catalyst: The pyridine nitrogen of PLP acts as an electron sink, stabilising carbanion intermediates during catalysis.
• Schiff Base Formation: The aldehyde group of PLP forms a Schiff base (C=N linkage) first with the lysine residue of the enzyme (internal aldimine) and then with the incoming substrate amino acid (external aldimine).
• Transfer of Amino Group: PLP oscillates between its aldehyde form (PLP) and its amine form (pyridoxamine phosphate, PMP), effectively shuttling the amino group from the substrate to the product.
• Versatility: PLP is not only required for transamination but also for decarboxylation, racemisation, and elimination reactions of amino acids. This makes it one of the most versatile coenzymes in biochemistry.
Vitamin B₆ Deficiency |
A deficiency of Vitamin B₆ (pyridoxine) impairs the activity of all PLP-dependent enzymes, disrupting amino acid metabolism, neurotransmitter synthesis (serotonin, dopamine, GABA), and porphyrin biosynthesis. Clinical features include peripheral neuropathy, dermatitis, glossitis, and anaemia. |
3.6 Examples of Important Transamination Reactions
Example 1: Alanine Aminotransferase (ALT) Reaction
L-Alanine + α-Ketoglutarate ⇌ Pyruvate + L-Glutamate
Significance: This reaction links amino acid catabolism with carbohydrate metabolism. Pyruvate produced here can enter the citric acid cycle (via acetyl-CoA) or be used for gluconeogenesis. This pathway is the basis of the glucose-alanine cycle between muscles and the liver.
Example 2: Aspartate Aminotransferase (AST) Reaction
L-Aspartate + α-Ketoglutarate ⇌ Oxaloacetate + L-Glutamate
Significance: This reaction is crucial for both the urea cycle (aspartate donates the second nitrogen atom in urea biosynthesis) and the malate-aspartate shuttle (which transfers reducing equivalents across the mitochondrial membrane).
Example 3: Branched-Chain Amino Acid Transamination
L-Leucine/Isoleucine/Valine + α-Ketoglutarate ⇌ Branched-chain α-Keto Acid + L-Glutamate
Significance: Branched-chain amino acids (BCAAs) — leucine, isoleucine, and valine — are primarily catabolised in skeletal muscle (not the liver). The carbon skeletons ultimately enter the citric acid cycle as acetyl-CoA and succinyl-CoA.
3.7 Biological Significance of Transamination
• Central Role in Amino Acid Catabolism: Transamination is the first and primary step in the degradation of most amino acids, funnelling nitrogen from multiple amino acids into glutamate.
• Funnelling of Nitrogen: By converging the amino groups of various amino acids onto α-ketoglutarate to form glutamate, transamination simplifies nitrogen metabolism. Glutamate then serves as the major nitrogen donor for the urea cycle.
• Linking Catabolism with Central Metabolism: The α-keto acids produced by transamination (pyruvate, oxaloacetate, α-ketoglutarate, etc.) are intermediates of glycolysis and the citric acid cycle, directly linking protein catabolism with energy metabolism.
• Biosynthesis of Non-Essential Amino Acids: Transamination operates in reverse for the synthesis of non-essential amino acids (e.g., alanine, aspartate, glutamate) from their corresponding keto acids, as long as nitrogen (in the form of glutamate) is available.
• Glucose–Alanine Cycle: During muscle activity, alanine produced by transamination of pyruvate in muscle is transported to the liver. In the liver, ALT catalyses the reverse reaction, regenerating pyruvate (for gluconeogenesis) and glutamate (for urea cycle), maintaining blood glucose and removing nitrogenous waste.
4. Deamination
4.1 Definition
Deamination is the biochemical process by which an amino group (–NH₂) is removed from an amino acid (or other nitrogen-containing compound), leading to the direct release of free ammonia (NH₃). Unlike transamination, which merely transfers the amino group, deamination results in the actual liberation of nitrogen as ammonia.
Deamination can occur by different mechanisms, broadly classified into three types: oxidative deamination, non-oxidative deamination, and hydrolytic deamination.
4.2 Types of Deamination
Type 1: Oxidative Deamination
In oxidative deamination, the amino acid is oxidised (loses electrons) while simultaneously losing its amino group as free ammonia. This process requires a coenzyme (NAD⁺ or NADP⁺) that accepts the electrons. The most important example is the oxidative deamination of L-glutamate by glutamate dehydrogenase. This is the primary mechanism by which nitrogen is converted into free ammonia in the body.
Amino Acid + NAD⁺ + H₂O → α-Keto Acid + NH₃ + NADH + H⁺
Type 2: Non-Oxidative Deamination
Some amino acids with hydroxyl (–OH), thiol (–SH), or imino groups can undergo deamination without any oxidation. These reactions are catalysed by lyases (elimination enzymes) and involve the elimination of water or hydrogen sulphide. PLP is generally required as a coenzyme.
• Serine dehydratase: Catalyses the dehydration-deamination of L-serine to produce pyruvate and NH₃.
L-Serine → [Serine dehydratase, PLP] → Pyruvate + NH₃
• Threonine dehydratase: Similarly converts L-threonine to α-ketobutyrate and NH₃.
L-Threonine → [Threonine dehydratase, PLP] → α-Ketobutyrate + NH₃
• Cysteine desulphydrase: Converts L-cysteine to pyruvate, NH₃, and H₂S.
L-Cysteine → Pyruvate + NH₃ + H₂S
• Histidine ammonia-lyase (histidase): Converts histidine to urocanate and NH₃.
Type 3: Hydrolytic Deamination
Certain amino acids with amide side chains (asparagine and glutamine) undergo hydrolytic deamination, in which water is added across the amide bond, cleaving it and releasing free ammonia. These reactions are catalysed by amidases — specifically asparaginase and glutaminase.
L-Asparagine + H₂O → [Asparaginase] → L-Aspartate + NH₃
L-Glutamine + H₂O → [Glutaminase] → L-Glutamate + NH₃
Note: Glutamine is the primary carrier of amino groups in the bloodstream. Hydrolytic deamination of glutamine in the kidney releases ammonia directly into the urine, which serves as an important buffering mechanism during acidosis.
4.3 Oxidative Deamination of Glutamate — The Central Reaction
Among all deamination reactions, the oxidative deamination of L-glutamate is by far the most physiologically significant and metabolically central. It represents the principal gateway through which amino group nitrogen exits the amino acid pool and enters the pathway of nitrogen excretion (urea cycle).
This reaction links transamination with deamination in what is called the 'transamination-deamination couple' or 'transdeamination':
Overall Equation
L-Glutamate + NAD⁺ (or NADP⁺) + H₂O ⇌ α-Ketoglutarate + NH₃ + NADH (or NADPH) + H⁺
Steps of Oxidative Deamination of Glutamate
The reaction proceeds in two discrete steps, both catalysed by the enzyme glutamate dehydrogenase:
• Step 1 — Oxidation (Dehydrogenation): NAD⁺ (or NADP⁺) accepts a hydride ion from the α-carbon of glutamate. This produces an imine intermediate called α-iminoglutarate (or glutamate-γ-semialdehyde-like intermediate) and NADH (or NADPH).
L-Glutamate + NAD⁺ → α-Iminoglutarate + NADH + H⁺
• Step 2 — Hydrolysis: Water hydrolyses the C=N double bond of α-iminoglutarate, releasing free ammonia (NH₃) and regenerating α-ketoglutarate.
α-Iminoglutarate + H₂O → α-Ketoglutarate + NH₃
The Transdeamination Couple |
Transamination + Oxidative Deamination together form the 'transdeamination' system, which is the predominant mechanism for nitrogen excretion from most amino acids: |
Step 1 (Transamination): Any Amino Acid + α-Ketoglutarate ⇌ Corresponding Keto Acid + Glutamate |
Step 2 (Oxidative Deamination): L-Glutamate + NAD⁺ + H₂O → α-Ketoglutarate + NH₃ + NADH + H⁺ |
Net Result: The amino group from any amino acid is converted to free NH₃, while α-ketoglutarate is regenerated (catalytic role) and NADH is produced (energy). |
4.4 Role of Glutamate Dehydrogenase (GDH)
Glutamate dehydrogenase (GDH) is a mitochondrial enzyme of extraordinary regulatory importance. It is the key enzyme linking the catabolism of amino acids with the citric acid cycle and the urea cycle. Key features of GDH include:
Location
GDH is found in the mitochondrial matrix of hepatocytes (liver cells), kidney cells, and brain cells. Its mitochondrial location ensures that the NH₃ produced is immediately available for carbamoyl phosphate synthetase I (the first enzyme of the urea cycle, also in mitochondria).
Coenzyme Duality
GDH can use either NAD⁺ or NADP⁺ as its electron acceptor, making it unique. In the catabolic direction (deamination), NAD⁺ is preferred; in the anabolic direction (reductive amination of α-ketoglutarate to form glutamate), NADPH is preferred.
Allosteric Regulation
Effector | Type | Metabolic Signal | Effect on Reaction |
ADP | Allosteric Activator | Low energy (ATP depleted) | Promotes deamination → more NADH, more NH₃ for urea cycle |
GTP / ATP | Allosteric Inhibitor | High energy state | Inhibits deamination → conserves amino acids |
Leucine | Allosteric Activator | Amino acid availability | Promotes deamination of glutamate |
NADH | Allosteric Inhibitor | High reducing power | Product inhibition — slows the reaction |
This elegant allosteric regulation ensures that GDH is active when energy is needed (low ADP:ATP ratio → deaminate amino acids for energy) and is inhibited when the cell is well-supplied with energy.
4.5 Formation and Fate of Ammonia
Ammonia (NH₃) is the primary nitrogenous waste product from amino acid deamination. It is produced from multiple sources in the body:
• Oxidative deamination of glutamate (primary source in the liver)
• Hydrolytic deamination of glutamine by glutaminase (especially in kidney and intestine)
• Purine nucleotide degradation (AMP → IMP + NH₃)
• Action of intestinal bacteria on dietary proteins
• Non-oxidative deamination of amino acids (serine, threonine)
Ammonia is highly toxic, especially to the central nervous system. Even at low concentrations, it can cause cerebral dysfunction, coma, and death (a condition called hepatic encephalopathy when arising from liver failure). Therefore, the body has evolved efficient mechanisms to:
• Transport ammonia safely in blood: Incorporated into glutamine (by glutamine synthetase in muscle and brain) — glutamine is the major non-toxic transport form of ammonia.
• Excrete nitrogen: In mammals (including humans), most ammonia is converted to urea in the liver via the urea cycle, which is then excreted by the kidney. In fish, ammonia is excreted directly (ammonotelic organisms). In birds and reptiles, it is excreted as uric acid (uricotelic organisms).
NH₃ + Glutamate + ATP → [Glutamine Synthetase] → Glutamine + ADP + Pi
(This reaction detoxifies ammonia in muscles and brain by incorporating it into glutamine for transport to the liver and kidney.)
5. Differences Between Transamination and Deamination
The following table provides a comprehensive comparison of transamination and deamination, which is frequently asked in university and competitive examinations:
Feature | Transamination | Deamination |
Definition | Transfer of amino group from an amino acid to a keto acid | Removal of amino group from an amino acid, releasing free NH₃ |
Free Ammonia Released? | NO — amino group is transferred, not released | YES — free ammonia (NH₃) is directly produced |
Reversibility | Fully reversible (equilibrium reaction) | Generally irreversible (especially oxidative deamination) |
Enzymes Involved | Aminotransferases / Transaminases (e.g., ALT, AST) | Oxidative: Glutamate dehydrogenase; Others: Serine dehydratase, Glutaminase, Asparaginase |
Coenzyme Required | Pyridoxal Phosphate (PLP) — always | NAD⁺ or NADP⁺ (oxidative type); PLP (non-oxidative type); none (hydrolytic) |
Substrates Used | Any amino acid + α-Ketoglutarate | Specific amino acids (glutamate, serine, threonine, asparagine, glutamine) |
Products Formed | New amino acid (glutamate) + new α-keto acid | α-Keto acid + NH₃ (+ NADH in oxidative type) |
Energy Change | No net oxidation; no energy change | Oxidative type produces NADH (energy yield: ~2.5 ATP/NADH) |
Types | One major type (amino group transfer) | Three types: Oxidative, Non-oxidative, Hydrolytic |
Primary Location | Cytoplasm and mitochondria (various tissues) | Mainly mitochondria of liver and kidney cells |
Role in Nitrogen Metabolism | Funnels nitrogen from various AAs into glutamate | Final release of nitrogen from glutamate as NH₃ for excretion |
Anabolic Role | YES — can synthesise non-essential amino acids | Limited — not primarily anabolic |
Link to Urea Cycle | Provides aspartate (2nd N source) and glutamate for urea cycle | Directly provides NH₃ (1st N source) for carbamoyl phosphate synthesis |
Key Example | L-Alanine + α-KG ⇌ Pyruvate + L-Glutamate (ALT reaction) | L-Glutamate + NAD⁺ + H₂O → α-KG + NH₃ + NADH (GDH reaction) |
6. Physiological Significance
6.1 Role in Energy Production
Amino acids contribute to energy production in a significant way, particularly during fasting, starvation, and prolonged aerobic exercise. The carbon skeletons resulting from transamination and deamination enter the citric acid cycle at specific points:
Entry Point into TCA Cycle | Amino Acids Entering Here | Direct Product |
Pyruvate | Alanine, Glycine, Serine, Cysteine, Threonine | Acetyl-CoA → 10 ATP |
Oxaloacetate (OAA) | Aspartate, Asparagine | Enter TCA directly → ~20 ATP/cycle turn |
α-Ketoglutarate | Glutamate, Glutamine, Proline, Histidine, Arginine | Enter TCA at step 3 → NADH, FADH₂ |
Succinyl-CoA | Methionine, Threonine, Valine, Isoleucine | GTP + FADH₂ + NADH production |
Fumarate | Phenylalanine, Tyrosine, Aspartate | Converted to Malate → OAA |
Acetyl-CoA | Leucine, Lysine, Tryptophan (ketogenic) | Complete oxidation via TCA → 10 ATP |
Each molecule of NADH generated by oxidative deamination yields approximately 2.5 ATP via oxidative phosphorylation, further underscoring the energetic contribution of amino acid catabolism.
6.2 Link with the Urea Cycle
The urea cycle (ornithine cycle) is the primary pathway for nitrogen excretion in terrestrial mammals. Transamination and deamination provide both nitrogen atoms that appear in the urea molecule:
• First Nitrogen of Urea: Comes from free NH₃ produced by oxidative deamination of glutamate by GDH. This NH₃ reacts with CO₂ and 2 ATP to form carbamoyl phosphate — the first committed step of the urea cycle, catalysed by Carbamoyl Phosphate Synthetase I (CPS-I) in liver mitochondria.
• Second Nitrogen of Urea: Comes from aspartate, which is produced by transamination of oxaloacetate with glutamate (via AST). Aspartate donates its amino group to argininosuccinate in the cytoplasmic portion of the urea cycle.
• Connection: This demonstrates an elegant coordination — transamination generates glutamate (nitrogen collector), deamination liberates NH₃ from glutamate (direct nitrogen for urea), and a second transamination produces aspartate (second nitrogen for urea). The urea cycle and citric acid cycle are also inter-linked through fumarate (formed in the urea cycle and entering the TCA cycle), forming the 'Krebs bicycle.'
6.3 Importance in Nitrogen Metabolism
• Nitrogen Balance: In healthy adults, nitrogen intake (from dietary protein) equals nitrogen excretion (as urea, creatinine, and other nitrogenous compounds) — a state called nitrogen equilibrium. Transamination and deamination are central to maintaining this balance.
• Positive Nitrogen Balance: During growth, pregnancy, and recovery from illness, more nitrogen is retained than excreted. Amino acid catabolism is reduced relative to protein synthesis.
• Negative Nitrogen Balance: During starvation, trauma, and severe illness, protein catabolism exceeds synthesis. More amino acids are degraded (via transamination and deamination), leading to muscle wasting and increased urea excretion.
• Amino Acid Pool Maintenance: Transamination, being reversible, helps maintain the pools of non-essential amino acids in the body by synthesising them from abundant keto acid precursors, thereby conserving essential amino acids.
• Neurotransmitter Metabolism: PLP-dependent transamination reactions are critical for the synthesis of neurotransmitters such as GABA (from glutamate), dopamine (from tyrosine), and serotonin (from tryptophan).
7. Clinical Importance
7.1 Liver Disorders and Aminotransferases
The liver is the primary organ for amino acid catabolism. It receives amino acids from the portal circulation (derived from intestinal protein digestion) and is responsible for most transamination, deamination, and urea cycle activities. Any hepatic injury disrupts these processes profoundly.
Hepatic Encephalopathy |
In severe liver disease (cirrhosis, acute hepatic failure), the liver's capacity for urea synthesis is diminished. Ammonia produced by transdeamination and by intestinal bacteria accumulates in the blood (hyperammonaemia). Ammonia crosses the blood-brain barrier, causing astrocyte swelling, glutamate depletion, altered neurotransmitter balance, and ultimately cerebral dysfunction — a condition called hepatic encephalopathy. Symptoms range from confusion and personality changes to deep coma and death. |
Treatment includes: dietary protein restriction, lactulose (traps NH₃ in colon), rifaximin (antibiotic to reduce intestinal ammonia-producing bacteria), and in severe cases, liver transplantation. |
7.2 Diagnostic Significance of Transaminase Enzymes (Liver Function Tests)
Under normal physiological conditions, aminotransferases (ALT and AST) are found predominantly within cells — their concentrations in the blood plasma are very low. When cells are damaged or destroyed (by disease, toxins, or infection), these intracellular enzymes leak into the bloodstream, causing a measurable rise in serum levels. This forms the basis of some of the most widely used clinical diagnostic tests:
Parameter | ALT (SGPT) | AST (SGOT) |
Full Name | Serum Glutamate Pyruvate Transaminase | Serum Glutamate Oxaloacetate Transaminase |
Normal Range (Adults) | 7–56 U/L | 10–40 U/L |
Tissue Specificity | Highly specific for liver | Less specific (liver, heart, muscle, kidney) |
Elevated in Liver Disease | Markedly elevated (most sensitive liver marker) | Elevated, but also rises in other conditions |
Elevated in Heart Attack | Minimally elevated | Markedly elevated (along with troponin, CK-MB) |
Clinical Use | Diagnosis of hepatitis (viral, alcoholic, drug-induced), cirrhosis, fatty liver | Diagnosis of hepatitis, myocardial infarction, muscle diseases |
AST:ALT Ratio (De Ritis Ratio) | Ratio < 1 suggests viral hepatitis | Ratio > 2 strongly suggests alcoholic hepatitis or cirrhosis |
Specific Clinical Conditions Where Aminotransferases are Elevated
• Viral Hepatitis (A, B, C, E): ALT and AST can rise to 10–100 times the upper normal limit. ALT > AST is characteristic.
• Alcoholic Liver Disease: AST:ALT ratio > 2:1 is a hallmark. Elevated γ-GT along with AST is suggestive.
• Drug-Induced Liver Injury (DILI): Paracetamol (acetaminophen) overdose causes dramatic elevation of both ALT and AST (can exceed 10,000 U/L in severe toxicity).
• Non-Alcoholic Fatty Liver Disease (NAFLD): Mild to moderate elevation, typically ALT > AST.
• Myocardial Infarction (Heart Attack): AST elevation along with troponin I/T and CK-MB confirms cardiac muscle damage.
• Muscle Diseases: Polymyositis, rhabdomyolysis — high AST and CK (creatine kinase).
7.3 Inborn Errors of Amino Acid Catabolism
Genetic defects in enzymes of amino acid catabolism lead to serious inherited metabolic diseases:
• Phenylketonuria (PKU): Deficiency of phenylalanine hydroxylase → accumulation of phenylalanine → intellectual disability.
• Maple Syrup Urine Disease (MSUD): Deficiency of branched-chain α-keto acid dehydrogenase → accumulation of branched-chain amino acids (leucine, isoleucine, valine) → CNS damage.
• Homocystinuria: Deficiency of cystathionine β-synthase (PLP-dependent) → accumulation of homocysteine → thrombosis, lens dislocation, intellectual disability.
• Hyperammonaemia: Deficiency of urea cycle enzymes (e.g., OTC deficiency) → ammonia accumulation → encephalopathy.
8. Conclusion
Amino acid catabolism is a fundamental and indispensable aspect of nitrogen metabolism in living organisms. The two key processes — transamination and deamination — work in an elegant, coordinated manner to efficiently remove amino groups from amino acids, channel nitrogen towards safe excretion, and provide carbon skeletons for energy generation and biosynthetic purposes.
Transamination, catalysed by PLP-dependent aminotransferases (notably ALT and AST), collects amino groups from diverse amino acids and concentrates them in glutamate. Deamination — predominantly the oxidative deamination of glutamate by glutamate dehydrogenase — then releases free ammonia, which enters the urea cycle for safe excretion as urea. The carbon skeletons produced enter the citric acid cycle, contributing to the cell's energy economy.
From a clinical perspective, aminotransferases have become invaluable diagnostic markers for liver and cardiac pathologies. Their elevation in serum reflects cellular injury and constitutes the foundation of liver function tests in modern clinical medicine.
In summary, understanding transamination and deamination provides the biochemical basis for comprehending nitrogen balance, protein metabolism, energy homeostasis, liver function, and the pathophysiology of numerous metabolic and hepatic disorders — making it one of the most important topics in biochemistry for life sciences students.
Key Points for Examination |
1. Transamination = amino group TRANSFER (no free NH₃ released); Deamination = amino group REMOVAL (free NH₃ produced). |
2. Pyridoxal Phosphate (PLP) = coenzyme for ALL aminotransferases and most amino acid reactions. |
3. Glutamate is the central amino group collector; Glutamate dehydrogenase (GDH) is the key enzyme for oxidative deamination. |
4. Transdeamination = Transamination + Oxidative Deamination of glutamate = the principal pathway for nitrogen excretion. |
5. ALT (GPT) is the most specific liver enzyme; AST (GOT) is elevated in both liver disease and myocardial infarction. |
6. AST:ALT ratio > 2 suggests alcoholic liver disease; ratio < 1 suggests viral hepatitis. |
7. GDH is activated by ADP (low energy) and inhibited by GTP/ATP (high energy) — allosteric regulation. |
8. Both nitrogen atoms of urea come from amino acid catabolism: 1st N from NH₃ (via GDH); 2nd N from aspartate (via AST transamination). |
MCQs (with Answers)
- Transamination requires:a) Vitamin Cb) PLP (Vitamin B₆) ✅c) Vitamin Dd) Iron
- Main amino group collector:a) Alanineb) Glutamate ✅c) Glycined) Serine
- Deamination releases:a) CO₂b) NH₃ ✅c) O₂d) ATP
- Enzyme for oxidative deamination:a) Hexokinaseb) Glutamate dehydrogenase ✅c) Amylased) Lipase
- ALT is used to detect:a) Kidney diseaseb) Liver damage ✅c) Heart attackd) Diabetes
- Transamination is:a) Irreversibleb) Reversible ✅c) One-wayd) Slow
- Toxic product of deamination:a) Ureab) Ammonia ✅c) Glucosed) Lactate
- Urea cycle occurs in:a) Kidneyb) Liver ✅c) Heartd) Brain
- AST acts on:a) Alanineb) Aspartate ✅c) Glycined) Proline
- Transdeamination involves:a) Only transaminationb) Only deaminationc) Both processes ✅d) Glycolysis
Exam Oriented Questions
- Define transamination
- Explain role of PLP
- Differentiate oxidative and non-oxidative deamination
- What is ammonia toxicity?
- Explain transdeamination
FAQs
References
• Lehninger, A.L., Nelson, D.L., & Cox, M.M. (2021). Lehninger Principles of Biochemistry (8th Edition). W.H. Freeman and Company, New York. [Chapters 18 & 19 — Amino Acid Oxidation and the Urea Cycle]
• Stryer, L., Berg, J.M., Tymoczko, J.L., & Gatto, G.J. (2019). Biochemistry (9th Edition). W.H. Freeman and Company, New York. [Chapter 23 — Protein Turnover and Amino Acid Catabolism]
• Harper, D.L., Murray, R.K., Granner, D.K., Mayes, P.A., & Rodwell, V.W. (2018). Harper's Illustrated Biochemistry (31st Edition). McGraw-Hill Education, New York. [Chapters 28 & 29 — Catabolism of Proteins and Amino Acid Nitrogen]
• Voet, D. & Voet, J.G. (2011). Biochemistry (4th Edition). John Wiley & Sons, New York. [Chapter 26 — Amino Acid Metabolism]
• Devlin, T.M. (Ed.) (2011). Textbook of Biochemistry with Clinical Correlations (7th Edition). John Wiley & Sons. [Chapter 11 — Amino Acid and Nitrogen Metabolism]
• Satyanarayana, U. & Chakrapani, U. (2013). Biochemistry (4th Edition). Books and Allied (P) Ltd., Kolkata. [Chapter 15 — Catabolism of Amino Acids]
• Moran, L.A., Horton, H.R., Scrimgeour, K.G., & Perry, M.D. (2012). Principles of Biochemistry (5th Edition). Pearson Education. [Chapter 17 — Amino Acid Metabolism]
• Garrett, R.H. & Grisham, C.M. (2012). Biochemistry (5th Edition). Brooks/Cole, Cengage Learning. [Chapter 26 — Nitrogen Acquisition and Amino Acid Metabolism]
• Braunwald, E. et al. (Eds.) (2022). Harrison's Principles of Internal Medicine (21st Edition). McGraw-Hill. [For clinical correlations of liver function tests and hepatic encephalopathy]
• Meister, A. (1962). Amino Acid Metabolism. Annual Review of Biochemistry, 31, 99–142. [Classic reference on transamination and deamination mechanisms]
• Cooper, A.J.L. & Plum, F. (1987). Biochemistry and physiology of brain ammonia. Physiological Reviews, 67(2), 440–519. [For clinical correlations of ammonia toxicity]
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