20241018_Amino_acid

The first stage of catabolism is Hydrolysis of complex molecules to their component building blocks, which includes the breakdown of Proteins into Amino acids, Carbohydrates into Monosaccharides, and Fats into Glycerol fatty acids.

The amino acid pool is connected to several metabolic pathways, including:

1. Urea Cycle - Converts ammonia (NH4+) into urea for excretion.
2. Krebs Cycle - Utilizes alpha-keto acids derived from the amino acid pool for energy production.
3. Synthesis of Biogenic Amines and Hormones - Produces important signaling molecules.
4. Synthesis of Purines and Pyrimidines - Involves carbamoyl phosphate and leads to nucleotides.
5. Creatine Pathway - Converts creatine to creatinine.
6. Porphyrin and Heme Synthesis - Involves the conversion of intermediates to heme and bilirubin.

The urea cycle converts ammonia (NH4+) into urea, which is a less toxic compound that can be excreted from the body. This process is crucial for detoxifying ammonia, a byproduct of amino acid metabolism, thus preventing toxic accumulation in the body.

Alpha-keto acids, produced from the amino acid pool, play a significant role in energy metabolism as they can enter the Krebs cycle. They are also involved in the synthesis of various biomolecules, including porphyrins, which are precursors to heme, and ultimately bilirubin.

Proteolytic enzymes and peptidases are responsible for digesting dietary proteins into amino acids in the gastrointestinal tract.

Most products of protein digestion circulate as amino acids in the body.

After a short fast, plasma amino nitrogen is approximately 5 mg/dl, while shortly after a protein-rich meal, it increases to about 8 mg/dl.

The measurement of plasma amino nitrogen is a good index of the content of amino acids in the blood.

The second stage of catabolism involves the Conversion of building blocks (Amino acids, Monosaccharides, Glycerol fatty acids) to acetyl CoA or other simple intermediates.

The third stage of catabolism focuses on the Oxidation of acetyl CoA and oxidative phosphorylation, which leads to the production of ATP and CO₂, and involves the TCA cycle.

1. Amino acids from cell breakdown
2. Amino acids from diet

• Synthesis of body proteins for cell structure, enzymes, hormones, and muscle contractile proteins.
• Energy production from amino-acid carbon skeletons, yielding on average 4 kcal/g.
• Synthesis of nonprotein nitrogen-containing compounds, such as serotonin.
• Glucose production from amino-acid carbon skeletons (in liver and kidney cells).
• Fat synthesis from amino-acid carbon skeletons (in liver cells, though generally minimal).

1. Urea synthesis occurs in the liver.
2. Excretion of urea is carried out by the kidneys.

An amino acid has a central carbon atom (α-carbon) bonded to:

• A hydrogen atom (H)
• A carboxyl group (COOH)
• An amino group (H2N)
• A side chain (R) that varies among different amino acids.

There are 20 naturally occurring amino acids found in proteins in humans.

The three groups of amino acids based on their side chain properties are:

1. Hydrophobic
2. Polar, uncharged
3. Polar, charged

The amino acids that belong to the hydrophobic group are:

1. Glycine
2. Alanine
3. Valine
4. Leucine
5. Isoleucine
6. Proline
7. Methionine
8. Phenylalanine
9. Tryptophan

The amino acids classified as polar, uncharged are:

1. Serine
2. Threonine
3. Cysteine
4. Tyrosine
5. Asparagine
6. Glutamine

The amino acids categorized as polar, charged are:

1. Aspartate
2. Glutamate
3. Lysine
4. Arginine
5. Histidine (at pH 6.0)

K

Arg

Group I amino acids have nonpolar side chains that consist of aliphatic or aromatic groups, exhibiting hydrophobic character. They are primarily found in the interior of large proteins due to their hydrocarbon nature, which results in little important chemical reactivity.

Group II amino acids possess polar, uncharged side chains at physiological pH, containing functional groups with at least one atom (N, O, or S) that can interact with water. A notable feature is the -SH group of cysteine, which can form a disulfide bond with another cysteine under oxidizing conditions, and can be reverted back to sulfhydryl groups by reducing agents.

Group III amino acids have polar, charged side chains at physiological pH, with functional groups that are either acidic (like aspartate and glutamate) or basic (like lysine, arginine, and histidine). These amino acids are hydrophilic and tend to cluster on the exterior of proteins in an aqueous environment.

An amide or peptide bond is formed when two amino acids are linked together.

• Polypeptides: Products with 10 to 100 amino acids.
• Proteins: Products with more than 100 amino acids.

Each amino acid incorporated into a polypeptide is called a residue.

Peptidases are enzymes that hydrolyze peptide bonds during the digestion of proteins in food.

Peptide sequences are written with the NH₃⁺-terminus on the left.

Amino acids can be abbreviated using either a three-letter symbol for short sequences or a one-letter symbol for long sequences.

The one-letter abbreviation for Alanine is A.

The three-letter abbreviation for Glycine is Gly.

The full name for the amino acid abbreviated as 'S' is Serine.

Cystine is formed from the oxidation of two cysteine residues, resulting in an -S-S- linkage between the two -SH groups of cysteine.

Cystine is equivalent to two molecules of cysteine, which are linked by a disulfide bond (-S-S-).

Under oxidizing conditions, two Cysteine molecules can form a Cystine molecule through the creation of a disulfide bond (S-S) between their thiol groups (SH). This reaction is reversible, meaning that under reducing conditions, Cystine can be converted back to two Cysteine molecules.

The hydroxylation of lysyl or prolyl residues is significant in the structure and function of collagen and elastin, which are essential for the integrity and elasticity of connective tissues.

Carboxylation of glutamate leads to the formation of y-carboxyglutamate, which is critical for the regulation of calcium metabolism in blood clotting.

The most common reversible modification of proteins is the phosphorylation of serine, threonine, and tyrosine residues, which can alter the enzymatic properties of the protein, thereby regulating various metabolic reactions.

Kinases are enzymes that catalyze the phosphorylation of proteins, leading to reversible modifications that regulate enzymatic reactions, such as the biosynthesis and breakdown of glycogen.

Elevated blood glucose in diabetes leads to the formation of glycosylated derivatives (HgA1c) through nonenzymatic reactions with blood proteins, contributing to the long-term pathology of the disease.

In uremic patients, the high concentration of urea in the blood results in the carbamoylation of hemoglobin at amino terminal residues, modifying its structure and function.

The two distinct ends of an amino acid chain are called the amino terminus (N-terminus) and the carboxyl terminus (C-terminus).

Peptides are conventionally written and numbered from the amino end (on the left) to the carboxyl terminus (on the right).

Small peptides like glutathione play important roles in regulating oxidation-reduction reactions and destroying deleterious free radicals in the cell.

Oxytocin and vasopressin are nonapeptides (small peptides) secreted by the pituitary gland that regulate dilation of blood vessels.

Enkephalins are peptides found in the brain and nervous system that play an important role in pain control.

The N-Terminal is the end of the peptide chain that has a free amino group (NH3+), while the C-Terminal is the end that has a free carboxyl group (COOH). This directionality is crucial for understanding protein synthesis and function.

The amino acid residues in a peptide chain are connected by amide bonds, also known as peptide bonds, which form between the carboxyl group of one amino acid and the amino group of another, releasing a molecule of water in the process.

Amino acid residues in a peptide chain are numbered sequentially from the N-Terminal (1) to the C-Terminal (5), indicating the direction of the peptide chain and the order of amino acids.

Glutathione (GSH) is composed of y-Glu, Cys, and Gly.

Reduced Glutathione (GSH) contains Cys-SH groups, while oxidized Glutathione (GSSG) contains Cys-S-S-Cys disulfide bonds.

Oxytocin is composed of the amino acids: Cys, Tyr, Ile, Gln, Asn, Pro, Leu, Gly.

Vasopressin consists of the amino acids: Cys, Tyr, Phe, Gln, Asn, Pro, Arg, Gly.

Leucine enkephalin is made up of the amino acids: Tyr, Gly, Gly, Phe, Leu.

Methionine enkephalin consists of the amino acids: Tyr, Gly, Gly, Phe, Met.

L-Aspartyl-L-phenylalanine methyl ester (aspartame) is a dipeptide composed of Aspartic acid and Phenylalanine with a methyl ester group.

Insulin is composed of two chains: A chain (21 amino acids) and B chain (30 amino acids), including amino acids such as Gly, Ala, Val, Cys, Leu, Glu, Arg, and others.

Leu-encephalin is a pentapeptide with the amino acid sequence: Tyrosine (Tyr), Glycine (Gly), Glycine (Gly), Phenylalanine (Phe), and Leucine (Leu). It is an opioid peptide that modulates the perception of pain.

A polypeptide chain consists of:

1. A constant backbone structure.
2. Variable side chains labeled as R1, R2, R3, R4, and R5, which determine the properties and functions of the polypeptide.

Proteins can be classified as monomeric (composed of a single polypeptide chain) or oligomeric (composed of two or more polypeptide chains).

Simple proteins are made up solely of amino acid residues, while conjugated proteins contain additional chemical groups, known as prosthetic groups, such as small organic molecules or metal atoms.

A protein with 250 amino acid residues has an approximate molecular weight of 27.5 kilodaltons.

The term 'multisubunit' refers to proteins that consist of multiple polypeptide chains, known as subunits, which may be identical or different.

The primary structure is the sequence of amino acid residues in a protein, derived from the sequence of nucleotide bases in DNA. It prepares the protein for the subsequent structural levels.

The secondary structure consists of localized regions of the primary structure that fold into structures such as α-helices or β-sheets.

The tertiary structure is formed when secondary structural elements interact and pack into a compact globular unit.

The primary structure of a protein is a linear chain of amino acids connected by peptide bonds. This sequence determines the protein's unique characteristics and function.

The two main types of secondary structures in proteins are:

1. Beta-pleated sheets - represented by zig-zagging strands connected by hydrogen bonds.
2. Alpha helices - depicted as a spiral ribbon with hydrogen bonds between the C=O and N-H groups within the helix.

The tertiary structure of a protein is characterized by its folded and complex 3D shape, which includes elements of both alpha helices and random loops. This structure is crucial for the protein's functionality.

The quaternary structure of a protein is defined by the assembly of multiple folded polypeptide chains that intertwine to form a larger, functional protein complex. These chains can be of different types, represented in various colors to indicate different subunits.

Enzymes act as biological catalysts that facilitate biochemical reactions to completion under mild conditions in the cell. Examples include amylase and aminotransferases.

Structural proteins provide mechanical support to cells and organisms. Examples include collagen, which is found in bone, skin, tendons, and cartilage, and keratin, found in feathers, hair, and fingernails.

Immune proteins are involved in defensive functions within the body. Examples include antibodies, snake venoms, and some toxins from plants.

Transport proteins move substrates throughout an organism for energy metabolism and the construction of cell components, such as lipoproteins. Storage proteins, like ferritin, store nutrients for future use.

Regulatory proteins, such as hormones like insulin and thyrotropin, regulate cellular and physiological activity. They include G proteins that transmit hormonal signals inside cells.

Receptor proteins are located in cell membranes and transmit regulatory messages inside the cell when small signal molecules, such as acetylcholine or epinephrine, bind to them on the surface of nerve cell membranes.

The proteins actin and myosin are the functional components of the contractile system in skeletal muscles, enabling muscle contraction and mobility.

Dynein is a protein that facilitates the movement of sperm and protozoa by their flagella and cilia, playing a crucial role in mobility.

The two main categories of proteins based on their solubility in water are globular proteins and fibrous proteins.

Globular proteins are more water soluble and play dynamic roles in transport, immune protection, and catalysis. They are dissolved in biological fluids such as blood and cytoplasm and have a relatively high content of amino acid residues with polar and charged R groups.

Fibrous proteins are water insoluble proteins, such as collagen and keratin. They contain a high content of amino acid residues with nonpolar R groups and have high tensile strength.

Globular proteins have a relatively high content of amino acid residues with polar and charged R groups, while fibrous proteins have a high content of amino acid residues with nonpolar R groups.

Phosphofructokinase is a glycolytic enzyme that catalyzes the transfer of a phosphate group from ATP to fructose 6-phosphate.

Citrate synthase combines acetyl-CoA and oxaloacetate to form citrate in the citric acid cycle.

Trypsin is a digestive enzyme that catalyzes protein hydrolysis in vertebrates.

Ribonuclease catalyzes RNA hydrolysis.

RNA polymerase catalyzes DNA-directed RNA synthesis in all organisms.

Reverse transcriptase catalyzes RNA-directed DNA synthesis, which is crucial for the replication of HIV.

Collagens are fibrous proteins that form cable networks serving as scaffolding for the support of tissues and organs in all animals.

Elastins have rubberlike properties that allow connective tissues, such as those in the lungs and large blood vessels, to stretch to several times their normal length.

Keratins are mechanically durable fibrous proteins found in vertebrates, primarily in the outer epidermal layer and its appendages like hair, nails, and feathers.

Antibodies are globular proteins produced by the immune system that participate in the destruction of biological invaders.

Interferons are proteins produced by higher animals that interfere with viral replication.

Interchain covalent cross-linkages in collagen lead to increasingly stiffer skin, blood vessels, and other tissues. This stiffness contributes to various medical problems associated with aging, such as reduced elasticity and increased fragility of tissues.

Diseases associated with the failure to form protein cross-linkages include homocystinuria, Wilson's disease, and Marfan's syndrome. These conditions highlight the importance of proper cross-linking for maintaining structural integrity in proteins.

Interchain covalent cross-linkages are not cleaved by proteolytic enzymes because they are not peptide bonds. This makes them more stable and resistant to enzymatic degradation compared to typical peptide linkages.

1. Synthesis of Body Proteins: Dietary proteins provide amino acids that are used to synthesize the body's proteins.

2. Energy Production: The carbon skeletons of amino acids can be oxidized to yield energy.

3. Synthesis of Nitrogen-Containing Metabolites: The carbon and nitrogen atoms from amino acids may be used to synthesize nitrogen-containing metabolites.

4. Source of Non-Nitrogen-Containing Substances: Dietary proteins can also serve as a source of non-nitrogen-containing substances, such as glucose.

The 'Amino Acid Pool' serves as a central reservoir for amino acids derived from dietary proteins through digestion and absorption. It facilitates the synthesis of body proteins, biogenic amines, hormones, and other metabolites. Additionally, it provides substrates for various metabolic pathways, including the Krebs cycle and urea cycle.

Dietary proteins are broken down during digestion and absorption, releasing amino acids that enter the 'Amino Acid Pool'. This process allows the body to utilize these amino acids for protein synthesis and other metabolic functions.

Kwashiorkor is characterized by:

• Swollen belly (edema)
• Emaciated body with muscle wasting
• Skin changes such as dermatitis
• Hair changes including discoloration and thinning
• Fatigue and irritability

Marasmus is characterized by:

• Severe weight loss and muscle wasting
• Visible ribs and frail limbs
• Lack of subcutaneous fat
• Growth retardation
• Weakness and lethargy

Beans are deficient in methionine. They can be replenished by consuming grains, nuts, or seeds.

Gastrin stimulates the release of pepsinogen from the stomach and also promotes the secretion of hydrochloric acid (HCl), which is necessary for the conversion of pepsinogen into pepsin.

Pepsinogen is an inactive zymogen that is converted into the active enzyme pepsin in the stomach. This conversion occurs when pepsinogen is cleaved by hydrochloric acid (HCl) at a low pH, specifically around pH 2.

The activation of pepsinogen results in the formation of pepsin and inert peptides, which are smaller protein fragments.

Secretin stimulates the secretion of a high concentration of bicarbonate in the duodenum, which helps to neutralize gastric acid and create an optimal pH for enzyme activity.

Pancreozymin, produced by the pancreas, triggers the release of zymogens such as chymotrypsinogen, trypsinogen, proelastase, and procarboxypeptidase, which are then activated into their respective endopeptidases.

Zymogens are activated through enzymatic cleavage; for example, trypsinogen is converted to trypsin by enteropeptidase, and chymotrypsinogen is converted to chymotrypsin by trypsin.

Endopeptidases, such as trypsin and chymotrypsin, cleave proteins at internal sites, while exopeptidases, like carboxypeptidases A and B, cleave amino acids from the carboxyl ends of polypeptide chains.

Trypsin cleaves at arginine and lysine bonds, while chymotrypsin cleaves at aromatic amino acid bonds.

Amino acids and small peptides are absorbed by stereospecific transport systems. Peptides are rapidly hydrolyzed by peptidases in the intestinal epithelial cells, releasing only amino acids into the portal blood. The uptake mechanisms for amino acids differ from those for peptides, with at least five stereospecific transport systems for amino acids present in the human intestine and kidney, which transport structurally similar amino acids.

Amino acid transport in the intestine often utilizes carrier-mediated transport systems that are coupled to sodium ion transport. This means that the transport of amino acids is linked to the movement of sodium ions across the intestinal membrane, facilitating the absorption process.

The neonatal intestine can absorb some milk proteins intact, including immunoglobulins from colostrum, which provide passive immunity. In contrast, normal adult intestinal mucosa can only absorb trace amounts of proteins, which may sometimes be antigenic and lead to health issues.

The initial step in the degradation of amino acids is the removal of the α-amino group from the rest of the molecule.

The major end products of nitrogen metabolism in humans are eliminated in the urine, primarily as urea. However, the immediate product of amino acid catabolism is ammonium ions (NH4+).

Ammonia is considered toxic because it is a direct product of amino acid catabolism, and its accumulation can lead to harmful effects in the body. Therefore, it must be efficiently removed from the system.

Ammonia is removed from the body through several mechanisms, primarily by converting it into less toxic substances such as urea, which is then excreted in the urine.

The general mechanism involves the oxidative deamination of glutamic acid coupled with specific aminotransferases (transaminases). The reaction can be summarized as:

amino acid₁ + keto acid₂ → keto acid₁ + amino acid₂

Glutamate dehydrogenase catalyzes the oxidative deamination of glutamic acid, regenerating α-ketoglutarate while producing ammonium ions and NADH. The reaction is represented as:

glutamate + NAD+ ↔ α-ketoglutarate + NADH + NH₄⁺

Most aminotransferases utilize glutamic acid and α-ketoglutarate as one of the common amino acid-keto acid pairs in transamination reactions.

Transamination is a biochemical process where an amino group from an amino acid is transferred to an alpha-keto acid, resulting in the formation of a new amino acid and a new alpha-keto acid. This process is crucial for amino acid metabolism and helps in the synthesis of non-essential amino acids.

a-Ketoglutarate acts as the acceptor of the amino group during the deamination process of amino acids, facilitating the conversion of amino acids into their corresponding keto acids.

The two forms of pyridoxal phosphate mentioned are Pyridoxamine phosphate and Pyridoxal phosphate, both of which are enzyme-bound forms involved in amino acid metabolism.

The deamination of amino acids with a-ketoglutarate results in the formation of keto acids and glutamate as a product of the reaction.

Transaminases facilitate the transfer of amino groups from amino acids to alpha-keto acids, resulting in the formation of corresponding alpha-keto acids and glutamate.

Glutamate dehydrogenase converts glutamate into alpha-ketoglutarate, producing NADH and NH4+ in the process, or it can convert alpha-ketoglutarate back to glutamate while consuming NAD+.

The removal of nitrogen atoms from amino acids is crucial for the detoxification of ammonia and the synthesis of urea, as well as for the production of energy and the formation of other biomolecules.

Glutamate dehydrogenase (GDH) plays a central role in the deamination of amino acids by facilitating the conversion of L-glutamate to α-ketoglutarate, producing NADH and ammonia (NH4+). It is unique as it is the only amino acid that has such an active dehydrogenase for the removal of amino groups.

The net reaction for the deamination of alanine using glutamate dehydrogenase is:

alanine + NAD+ + H2O → pyruvate + NADH + NH4+

Transamination between alanine and α-ketoglutarate occurs as follows:

alanine + α-ketoglutarate → pyruvate + glutamate

This process involves the transfer of the amino group from alanine to α-ketoglutarate, forming pyruvate and glutamate.

L-amino acid oxidases are enzymes that deaminate amino acids in the kidney and liver, although they are less important in amino acid catabolism. They have broad specificity, allowing many different amino acids to serve as substrates, but their rates of oxidation are relatively slow.

The tightly bound coenzyme of L-amino acid oxidase from the kidney is flavin mononucleotide (FMN).

D-amino acid oxidases use flavin adenine dinucleotide (FAD) as their coenzyme and are mainly present in bacteria and other microorganisms, whereas L-amino acid oxidases use FMN and are found in the kidney and liver.

The products of the reaction are alpha-Keto acids, NH4+, and H2O2. Additionally, FMN is converted to FMNH2 and then back to FMN during the process.

Catalase converts H2O2 into H2O and 1/2 O2, helping to reduce the potentially harmful effects of hydrogen peroxide produced during the reaction.

FMN acts as a cofactor in the reaction, being reduced to FMNH2 during the conversion of L-amino acids to alpha-keto acids and then regenerated back to FMN.

The three principal routes for the metabolic disposal of ammonia are:

1. Urea formation - converting ammonia to urea for excretion.
2. Glutamate synthesis - incorporating ammonia into glutamate.
3. Glutamine synthesis - converting ammonia into glutamine for transport and storage.

A fourth minor route is the formation of asparagine.

Impaired urea formation can lead to ammonia intoxication, which may occur in patients with conditions such as hepatomegaly and impaired liver function.

Ammonia is extremely toxic at high concentrations, so it must be converted to nontoxic metabolites to prevent toxicity and allow for its reuse or excretion based on the body's needs.

The primary function of the Urea Cycle is to convert toxic ammonia into urea for excretion from the body.

The two main compartments involved in the Urea Cycle are the cytosol and the mitochondrion.

Arginine is converted to Argininosuccinate, which then releases Fumarate and is further converted to Citrulline in the cytosol.

Carbamoyl phosphate is formed in the mitochondrion from Citrulline with the addition of 2 ATP, CO2, NH3, and H2O, releasing 2 ADP and Pi.

Aspartate provides an incoming amino group via transamination from glutamate, which is crucial for the conversion of Argininosuccinate to Citrulline.

The final product of the Urea Cycle is Urea, which is excreted from the body.

The defective enzyme in congenital hyperammonemia type I is carbamoyl phosphate synthetase.

Symptoms include episodic vomiting, psychomotor retardation, and stupor, which respond to a restricted protein diet.

The defective enzyme in congenital hyperammonemia type II is ornithine transcarbamoylase.

In citrullinemia, the defective enzyme acts on citrulline, and in argininosuccinic acidemia, the defective enzyme acts on argininosuccinate.

The glutamine concentration of the blood is often elevated in patients with congenital hyperammonemia.

Carbamoyl phosphate is a key component in the urea cycle that combines with L-Ornithine to form L-Citrulline, facilitating the conversion of toxic ammonia into urea.

Type I hyperammonemia results from a deficiency in the enzyme carbamoyl phosphate synthetase I, leading to the accumulation of ammonia and toxic intermediates, which can cause severe neurological damage and other health issues.

Type II hyperammonemia is caused by a deficiency in the enzyme ornithine transcarbamylase, leading to similar symptoms as Type I but with different metabolic disruptions and accumulation of specific intermediates.

L-Argininosuccinate is an intermediate in the urea cycle formed from L-Citrulline and L-Aspartate, which is then converted into L-Arginine and fumarate, playing a crucial role in the detoxification of ammonia.

Genetic disorders associated with defects in the urea cycle include Type I hyperammonemia, Type II hyperammonemia, Citrullinuria, Argininosuccinic acidemia, and Arginase deficiency, each affecting different enzymes and leading to toxic accumulation.

The carbon skeleton of amino acids can be used to produce metabolic energy. Depending on their classification, they can contribute to the formation of ketone bodies or glucose/glycogen.

The end products of glycine degradation are CO2 and NH3. The enzyme that facilitates the conversion of serine to tetrahydrofolate is serine hydroxymethyltransferase.

Phenylalanine hydroxylase converts L-Phenylalanine to L-Tyrosine and requires Tetrahydrobiopterin and O2 as cofactors, producing Dihydrobiopterin and H2O as byproducts.

The final products of L-Tyrosine degradation are Fumarate and Acetoacetate.

Acetyl CoA serves as a key entry point for several amino acids into the citric acid cycle, allowing them to be metabolized for energy production and biosynthesis.

The amino acids associated with α-Ketoglutarate include Arginine, Glutamate, Glutamine, Histidine, and Proline.

Amino acids enter the citric acid cycle at various points, contributing to the cycle's intermediates and facilitating energy production and metabolic pathways.

The amino acids that enter at Pyruvate include Alanine, Cysteine, Glycine, Serine, and Tryptophan.

The citric acid cycle is crucial for the catabolism of amino acids, allowing for the conversion of their carbon skeletons into energy and other metabolic intermediates.

Isoleucine, Methionine, Threonine, and Valine are linked to Succinyl CoA in the citric acid cycle.

Key intermediates formed in the citric acid cycle relevant to amino acid metabolism include Citrate, Isocitrate, α-Ketoglutarate, Succinyl CoA, Succinate, Fumarate, Malate, and Oxaloacetate.

Essential amino acids cannot be synthesized by humans and must be obtained from the diet.

Several nonessential amino acids are synthesized from the carbon skeletons of intermediates in metabolic pathways such as the Krebs cycle and the glycolytic pathway.

Alpha-ketoglutarate is a key intermediate in the Krebs cycle that is converted into glutamate through the action of the enzyme glutamate dehydrogenase. This conversion is crucial for the synthesis of several amino acids, including glutamine and proline.

Oxaloacetate is converted into aspartate by the enzyme aspartate transaminase (AST). Aspartate can then be further utilized to synthesize other amino acids such as asparagine and methionine.

Pyruvate is converted into alanine through the action of the enzyme alanine transaminase (ALT). This reaction is significant as it links carbohydrate metabolism to amino acid synthesis, allowing for the production of alanine from glucose-derived pyruvate.

Amino acids serve as precursors for the synthesis of important amine compounds, including neurotransmitters such as serotonin, catecholamines (epinephrine, norepinephrine, L-dopa), and histamine. The synthesis of these substances can be influenced by dietary intake, such as high levels of tryptophan increasing serotonin production, which may lead to drowsiness.

The biosynthetic pathway for Heme production involves the following steps:

1. Succinyl CoA + Glycine combine to form δ-Aminolevulinate.
2. δ-Aminolevulinate is then converted to Porphobilinogen.

Choline is synthesized through the following pathway:

1. Phosphatidylserine is converted to Phosphatidylethanolamine.
2. Phosphatidylethanolamine is then converted to Phosphatidylcholine.

The biosynthesis of Glycosamine involves:

1. Fructose 6-phosphate and Glutamine combine to form Glutamate.
2. Glutamate is then converted to Glucosamine 6-phosphate.

Nucleotide biosynthesis involves the following amino acids:

• Glycine
• Glutamine
• Aspartic acid

These amino acids contribute nitrogen to form Purine and pyrimidine nucleotides.

In protein synthesis, all amino acids are utilized to form proteins through a series of translation processes.

Biogenic amines are produced from amino acids through the following process:

• Amino acids are converted into hormones, neurotransmitters, and pharmacologic amines.

Carnitine is synthesized from:

1. Lysine and Methionine combine to form Carnitine.

The synthesis of Creatine phosphate involves:

1. Arginine, glycine, and methionine are used to produce Creatine phosphate.

The recommended daily allowance (RDA) is 0.8g of protein per kg of body weight, which is approximately 66g of protein per day for an adult weighing 75 kg.

For athletes, the recommended daily allowance (RDA) is 1.2-1.4g of protein per kg of body weight, which is necessary for muscle maintenance and training recovery.

Populations at higher risk of protein deficiency include:

1. Children in Central Africa and South Asia (up to 30% with inadequate intake)
2. Vegetarians and vegans with imbalanced diets
3. Institutionalized older adults
4. Hospitalized patients

Long-term protein deficiency can lead to:

1. Muscle wasting
2. Edema due to low serum albumin concentration, which affects oncotic pressure
3. Fatty liver from impaired lipoprotein synthesis
4. Skin, hair, and nail problems
5. Increased severity of infections

Low protein intake may:

• Increase appetite
• Promote overeating
• Contribute to the risk of obesity

1. Marasmus: Characterized by inadequate energy in all forms, including proteins. Patients are emaciated, with body weight reduced to less than 62% of normal, showing clinical signs of muscle wasting and loss of subcutaneous fat.

2. Kwashiorkor: Also known as edematous malnutrition, caused by a lack of protein in the diet despite normal energy intake. Early treatment with extra calories and proteins can lead to full recovery, while late treatment may result in stunted growth and mental and physical disabilities.

The exceptions that contain a complete set of essential amino acids are soya bean and quinoa.