1. AMINO ACID POOL
Free amino acids are present throughout the body, in cells, blood, and the extracellular fluids. This pool is supplied by three sources:
1. Amino acids provided by the degradation of body proteins
2. Amino acids derived from dietary protein
3. Synthesis of nonessential amino acids from simple intermediates of metabolism.
The amino pool is depleted by three routes:
1. Synthesis of body protein
2. Amino acids consumed as precursors of essential nitrogen-containing small molecules
3. Conversion of amino acids to glucose, glycogen, fatty acids, ketone bodies, or CO2 + H2O
The amino acid pool is small (about g of amino acids) in comparison with the amount of protein in the body (about 12 kg in a 70-kg man), it is conceptually at the center of whole-body nitrogen metabolism.

2. PROTEIN TURNOVER
Most proteins in the body are constantly being synthesized and then degraded, permitting the removal of abnormal or unneeded proteins.
1. Rate of turnover: In healthy adults, the total amount of protein in the body remains constant, because the rate of protein synthesis is just sufficient to replace the protein that is degraded. This process, called protein turnover, leads to the hydrolysis and resynthesis of g of body protein each day. Short-lived proteins (regulatory proteins and misfolded proteins) are rapidly degraded, in minutes or hours. Long-lived proteins, with half-lives of days to weeks, constitute the majority of proteins in the cell. Structural proteins, such as collagen, have half-lives measured in months or years.
2. Protein degradation: Two major enzyme systems responsible for degrading damaged or unneeded proteins:
- ATP-dependent ubiquitin-proteasome system of the cytosol for endogenous proteins
- ATP-independent degradative enzyme system of the lysosomes degrade primarily extracellular proteins, such as plasma proteins.
In healthy, well-fed individuals, the input to the amino acid pool is balanced by the output, that is, the amount of amino acids contained in the pool is constant. The amino acid pool is said to be in a steady state, and the individual is said to be in nitrogen balance.

3. Glucogenic and Ketogenic
GLUCOGENIC AMINO ACIDS
Leucine
Lysine
Isoleucine
Phenyl-alanine
Tryptophan
Histidine
Methionine
Threonine
Valine
Tyrosine
Alanine
Arginine
Asparagine
Aspartate
Cysteine
Glutamate
Glutamine
Glycine
Proline
Serine
Ketogenic
Glucogenic and Ketogenic
Glucogenic
Essential
Nonessential
Amino acids whose catabolism yields pyruvate or one of the intermediates of the citric acid cycle are termed glucogenic. These intermediates are substrates for gluconeogenesis and can give rise to the net formation of glucose in the liver and kidney.
Ketogenic amino acids
Amino acids whose catabolism yields either acetoacetate or one of its precursors (acetyl CoA or acetoacetyl CoA). Leucine and lysine are the only exclusively ketogenic amino acids found in proteins.

4. Origins of non-essential amino acids (i. e
Origins of non-essential amino acids (i.e. those not required in a normal diet).
Essential amino acids (i.e. those required in the diet).

5. DIETARY PROTEIN
Humans have no dietary requirement for protein. Nine of the 20 amino acids needed for the synthesis of body proteins are essential – that is, they cannot be synthesized in humans.
1. Proteins from animal sources: Proteins from animal sources (meat, poultry, milk, and fish) have a high quality because they contain all the essential amino acids in proportions similar to those required for synthesis of human tissue proteins.
2. Proteins from plant sources: Proteins from wheat, corn, rice, and beans have a lower quality than do animal proteins. However, proteins from different plant sources may be combined in such a way that the result is equivalent in nutritional value to animal protein. For example, wheat (lysine-deficient but methionine-rich) may be combined with kidney beans (methionine-poor but lysine-rich) to produce an improved biologic value. Thus, eating foods with different amino acids during the day can result in a dietary combination with a higher biologic value than either of the component proteins.
PDCAAS
Source value
Animal proteins
Egg 1.0
Milk protein 1.0
Beef/poultry/fish
Gelatin 0.08
Plant proteins
Soybean protein 1.0
Kidney Beans 0.68
Whole wheat bread 0.40

6. Protein energy (calorie) malnutrition (PEV)
Affected individuals show a variety of symptoms, including a depressed immune system with a reduced ability to resist infection. Death from secondary infection is common. Two extreme forms of PEM are kwashiorkor and marasmus.
1. Kwashiorkor: Kwashiorkor occurs when protein deprivation is relatively greater than the reduction in total calories. Kwashiorkor is frequently seen in children when their diet consists predominantly of carbohydrates. Typical symptoms include stunted growth, edema, skin lesions, depigmented hair, anorexia, enlarged fatty liver, and decreased plasma albumin concentration.
2. Marasmus: Marasmus occurs when calorie deprivation is relatively greater then the reduction in protein. Typical symptoms include arrested growth, extreme muscle wasting, weakness, and anemia. Victims of marasmus do not show the edema or changes in plasma proteins observed in kwashiorkor.
CHARACTERISTIC
KWASHIORKOR
MARASMUS
Weight for age (% expected)
60-80
<60
Weight for height
Normal of decreased
Markedly decreased
Edema
Present
Absent
Mood
Irritable when picked up; apathetic when left alone
Alert, irritable
Appetite
Poor
Good

7. DIGESTION OF DIETARY PROTEINS
Most of the nitrogen in the diet is consumed in the form of protein, typically amounting to g/day. Proteins are generally too large to be absorbed by the intestine. They must, therefore, be hydrolyzed to yield di- and tripeptides as well as individual amino acids, which can be absorbed. Proteolytic enzymes responsible for degrading proteins are produced by three different organs: the stomach, the pancreas, and the small intestine.
Digestion of proteins by gastric secretion
The digestion of proteins begins in the stomach, which secretes gastric juice – a unique solution containing hydrochloric acid and the proenzyme, pepsinogen.
1. Hydrochloric acid: Stomach acid is too dilute (pH 2-3) to hydrolyze proteins. The acid, secreted by the parietal cells, functions to denature proteins, thus making them more susceptible to subsequent hydrolysis by proteases.
2. Pepsin: This acid-stable endopeptidase is secreted by the chief cells of the stomach as an inactive zymogen (or proenzyme), pepsinogen. In general, zymogens contain extra amino acids in their sequences that prevent them from being catalytically active. Pepsinogen is activated to pepsin, either by HCI, or autocatalytically by other pepsin molecules that have already been activated. Pepsin releases peptides and a few free amino acids from dietary proteins.

8. Digestion of proteins by pancreatic enzymes
On entering the small intestine, large polypeptides are further cleaved to oligopeptides and amino acids by a group of pancreatic proteases.
1. Specificity: Each of these enzymes has a different specificity for the amino acid R-groups adjacent to the susceptible peptide bond. For example, trypsin cleaves only when the carbonyl group of the peptide bond is contributed by arginine or lysine. These enzymes, are synthesized and secreted as inactive zymogens.
2. Release of zymogens: The release and activation of the pancreatic zymogens is mediated by the secretion of cholecystokinin and secretin, two polypeptide hormones of the digestive tract.
3. Activation of zymogens: Enteropeptidase converts the pancreatic zymogen trypsinogen to trypsin by removal of a hexapeptide from the N-terminus of trypsinogen. Trypsin subsequently converts other trypsinogen molecules to trypsin by cleaving a limited number of specific peptide bonds in the zymogen. Enteropeptidase thus unleashes a cascade of proteolytic activity, because trypsin is the common activator of all the pancreatic zymogens.

9. Protein digestive enzymes
SOURCE
ZYMOGEN
ACTIVATION
SUBSTRATE
END PRODUCT
stomach
fundus
pylorus
pepsinogen A
pepsinogen B
HCl
pH 1-2
autoactivation
protein
peptides
pancreas
trypsinogen
chymotrypsinogen
proelastase
procarboxy-
peptidases
enteropeptidase trypsin
trypsin
protein, peptides
polypeptides at
-COOH end
polypeptides
dipeptides
as for trypsin
small peptides
amino acids
ENZYME
small intestine (no inactive precursor)
aminopeptidase
dipeptidases
endopeptidases
not applicable
polypeptides at –NH2
end dipeptides

10. Characteristics of the substrate-binding sites in the serine proteases chymotrypsin, trypsin, and elastase, which hydrolyse peptide bonds. In chymotrypsin a hydrophobic pocket binds aromatic amino acid residues such as phenylalanine (Phe). In trypsin, the negative charge of the aspartate residue in the active site promotes cleavage to the carboxyl side of positively charged lysine (Lys) and arginine (Arg) residues. In elastase, valine and threonine block the binding site and permit binding of amino acids with small side chains, such as glycine (Gly).

11. TRANSPORT OF AMINO ACIDS INTO CELLS
The concentration of free amino acids in the extracellular fluids is significantly lower than that within the cells of the body. This concentration gradient is maintained because active transport systems, driven by the hydrolysis of ATP, are required for movement of amino acids from the extracellular space into cells. At least seven different transport systems are known that have overlapping specificities for different amino acids. The small intestine and the proximal tubule of the kidney have common transport systems results in an inability to absorb particular amino acids into the gut and into the kidney tubules. One system is responsible for the uptake of cystine and the dibasic amino acids, ornithine, arginine, and lysine. In the inherited disorder cystinuria, this carrier system is defective, and all four amino acids appear in the urine. Cystinuria occurs at a frequency of 1 in 7,000 individuals, making it one of the most common inherited diseases, and the most common genetic error of amino acid transport. The disease expresses itself clinically by the precipitation of cystine to form kidney stones, which can block the urinary tract. Oral hydration is an important part of treatment for this disorder. Defects in the transport of tryptophan can result in Hartnup disorder and pellagra-like dermatologic and neurologic symptoms.

12. REMOVAL OF NITROGEN FROM AMINO ACIDS
Removing the α-amino group is essential for producing energy from any amino acid, and is an obligatory step in the catabolism of all amino acids. Once removed, this nitrogen can be incorporated into other compounds or excreted, with the carbon skeletons being metabolized.
Transamination: the funneling of amino groups to glutamate
The first step in the catabolism of most amino acids is the transfer of their α-amino group to α-ketoglutarate. The products are an α-keto acid and glutamate. α-Ketoglutarate plays a pivotal role in amino acid metabolism by accepting the amino groups from most amino acids. Transfer of amino groups from one carbon skeleton to another is catalyzed by a family of enzymes called aminotransferases (transaminases). All amino acids, with the exception of lysine and threonine, participate in transamination at some point in their catabolism.

13. Mechanism of action of aminotransferases
All aminotransferases require the coenzyme pyridoxal phosphate, which is covalently linked to the ε-amino group of a specific lysine residue at the active site of the enzyme. Aminotransferases act by transferring the amino group of an amino acid to the pyridoxal part of the coenzyme to generate pyridoxamine phosphate. The pyridoxamine form of the coenzyme then reacts with an α-keto acid to form an amino acid, at the same time regenerating the original aldehyde form of the coenzyme.

14. Diagnostic value of plasma aminotransferases: Aminotransferases are normally intracellular enzymes, with the low levels found in the plasma. The presence of elevated plasma levels of aminotransferases indicates damage of cells rich in these enzymes.
- Alanine aminotransferase (ALT): The enzyme catalyzes the transfer of the amino group of alanine to α-ketoglutarate, resulting in the formation of pyruvate and glutamate. The reaction is readily reversible. During amino acid catabolism, this enzyme functions in the direction of glutamate synthesis. Thus, glutamate acts as a “collector” of nitrogen from alanine.
- Aspartate aminotransferase (AST): AST is an exception to the rule that aminotransferases funnel amino groups to form glutamate. During amino acid catabolism, AST transfers amino groups from glutamate to oxaloacetate, forming aspartate, which is used as a source of nitrogen in the urea cycle.
- Liver disease: Plasma AST and ALT are elevated in nearly all liver diseases, but are particularly high in viral hepatitis, toxic injury, and prolonged circulatory collapse. ALT is more specific than AST for liver disease. Serial enzyme measurements are often useful in determining the course of liver damage.
-Nonhepatic disease: Aminotransferases may be elevated in nonhepatic disease, such as myocardial infarction and muscle disorders.

15. GLUTAMATE DEHYDROGENASE: THE OXIDATIVE DEAMINATION OF AMINO ACIDS
Oxidative deamination by glutamate dehydrogenase results in the liberation of the amino group as free ammonia (NH3). These reactions occur primarily in the liver and kidney. They provide α-keto acids that can enter the central pathway of energy metabolism, and ammonia, which is a source of nitrogen in urea synthesis.
Glutamate dehydrogenase: Glutamate is unique in that it is the only amino acid that undergoes rapid oxidative deamination – a reaction catalyzed by glutamate dehydrogenase. Therefore, the sequential action of transamination (resulting in the collection of amino groups from most amino acids onto α-ketoglutarate to produce glutamate) and the oxidative deamination of that glutamate provide a pathway whereby the amino groups of most amino acids can be released as ammonia.
- Coenzymes: Glutamate dehydrogenase is unusual in that it can use either NAD+ of NADP+ as a coenzyme (NAD+ in oxidative deamination and NADPH in reductive amination)
- Allosteric regulators: Guanosine triphosphate (GTP) is an allosteric inhibitor of glutamate dehydrogenase, whereas adenosine diphosphate (ADP) is an activator. Thus, when energy levels are low in the cell, amino acid degradation by glutamate dehydrogenase is high, facilitating energy production from the carbon skeletons derived from amino acids.