INTRODUCTION

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A Partial Roadmap For Amino Acid Metabolism
 

Summary

Blood Provides A Pool Of Amino Acids For Use By Cells
 

Summary AA Equilibrium

There are no storage molecules for amino acids as there are for carbohydrates, i.e., glucose in glycogen, or for fatty acids, as in triacylglycerols (fats). The body maintains a relatively large free amino acid pool in the blood (approximately 35-65 mg/deciLiter), even during fasting; cells and tissues have continuous access to individual amino acids for the synthesis of proteins and essential amino acid derivatives. The blood concentrations of two amino acids, alanine and glutamine, which serve special purposes, are higher than those of the other amino acids.

Processes That Use Amino Acids
Protein Synthesis

Summary AA Use Protein Synthesis

Proteins in the body are constantly synthesized and degraded, partially draining and refilling the cellular amino acid pools. In a well fed, healthy human adult, approximately 300 - 600 grams of new protein are synthesized each day. Growth factors, hormones, including insulin, and cytokines stimulate protein synthesis.

Processes That Use Amino Acids
Synthesis Of Other Nitrogen-Containing Molecules

Summary AA Use Protein Synthesis

All the useful nitrogen in the body is supplied by amino acids. All nitrogen-containing compounds synthesized in the body derive their nitrogen from amino acids — cellular proteins, hormones (e.g., thyroxine, epinephrine, insulin), neurotransmitters, creatine phosphate, heme in hemoglobin and cytochromes, melanin, purine and pyrimidine bases. This is only a partial list of all the nitrogen-containing compounds that derive their nitrogen from amino acids.

Synthesis Of Other Nitrogen-Containing Molecules
An Example — Creatinine

Creatinine Synthesis 1

Creatinine is a nitrogen-containing molecule synthesized predominantly in muscles. Creatine is synthesized first from argining, glycine and S-adenosyl methionine (SAM).

Synthesis Of Other Nitrogen-Containing Molecules
An Example — Creatinine

Creatinine Synthesis 1

Creatine (phospho) kinase converts creatine to creatine phosphate, which accumulates in muscle cells as an energy buffer when ATP is aboundant. Its phosphate group is readily donated to ADP, thereby boosting the ATP content of the muscle celln as they hydrolyse ATP for energy to derive muscle contraction.

Synthesis Of Other Nitrogen-Containing Molecules
An Example — Creatinine

Creatinine Synthesis 1

Creatine phosphate is spontaneously (non-enzymatically) dephosphorylated, resulting in the cyclization of the dephosphorylated molecule to yield creatinine, which ...

Synthesis Of Other Nitrogen-Containing Molecules
An Example — Creatinine

Creatinine Synthesis 1

is readily excreted in the urine. The amount of creatinine produced is proportional to the muscle mass and is released from muscle at a constant rate. The amount excreted in the urine per day per person is constant and independent of the volume of urine excreted. Elevataed creatinine in the blood relates to impaired kidney function, i.e., impared Glomerular Flow Rate (GFR). Creatinine clearance rate (C or CrCl) is the volume of blood plasma that is cleared of creatinine per unit time and is a useful measure for approximating the GFR. Because creatinine excretion per day per person is constant, excreted creatinine serves as an internal standard in the urine against which the excretion of other molecules can be measured, e.g., drugs or their metabolites.

Processes That Use Amino Acids
Degradation Of Amino Acids

Summary AA Use Protein Synthesis

Amino acids are continuously degraded. Their nitrogen is removed either by deamination or by transamination reactions that donate it to various α-keto acids (see “Nitrogen” in the top menu). Ultimately, the nitrogen is excreted, mainly as urea, but also as NH4+ or other nitrogen-containing compounds. Normally, urea accounts for about 90% of all excreted nitrogen. Amino acid carbon skeletins are reused for the synthesis of other molecules, are a major source of carbon skeletons for the synthesis of glucose (gluconeogenesis) or are oxidized for the production of energy.

Processes That Contribute Amino Acids
Dietary Protein

Summary AA Contribution Protein Synthesis

Average adult humans require approximately 60 - 100 grams of dietary protein per day. Amino acids are produced by digestion of dietary proteins in the intestines, absorbed through the intestinal epithelial cells, and enter the blood. Various cells take up these amino acids, which enter the cellular amino acid pools. Amino acids are used for the synthesis of proteins and other nitrogen-containing compounds, or their carbon skeletons are oxidized for energy or the synthesis of glucose.

Processes That Contribute Amino Acids
Dietary Protein — Failure To Injest Adequate Protein: Kwashiorkor

Summary AA Contribution Protein Synthesis

Failure to injest sufficient protein results in kwashiokor. Kwashiorkor is a state of malnutrition that results from a deficiency of dietary protein in the presence of a normal or high carbohydrate intake. Kwashiorkor is most common between the ages of 1 and 4 years, but can occur in infancy. There are many causes of kwashiorkor, but weaning is the major factor, when breast milk is replaced by an inadequate and often unbalanced diet. Infants are most frequently affected in times of famine, when their mother is also starved for protein. Kwashiorkor symptoms may develop slowly over time. Common symptoms include: abdominal swelling, distension or bloating, diarrhea, enlarged, fatty liver, fatigue, frequent infections, generalized swelling, hair and nail changes, including brittle, reddish hair and ridged nails that are thin and soft, Irritability, muscle wasting, skin changes, including pigment loss, red or purple patches, peeling, cracking, skin sloughing, and the development of sores, slowed growth leading to short stature, weight loss. Treatment is protein supplementation often in the form of dried skim milk.

Processes That Contribute Amino Acids
Protein Degradation

Summary AA Contribution Protein Synthesis

In a well fed, healthy human adult, approximately 300 - 600 grams of protein are degraded to amino acids each day. Normally, this degradation is balanced by the synthesis of 300 - 600 grams of protein per day. Protein turnover allows changes in the quantities of different proteins produced as physiology requires, and removes modified or damaged proteins. Decreased insulin shifts the balance between protein synthesis and protein degradation toward degradation, resulting in a net loss of protein. During some “chronic stresses” cellular proteins are degraded to provide amino acids for functions that help alleviate the stress (see “Hypothelamic-Pituitary-Adrenal Axis” below).

Processes That Contribute Amino Acids
Synthesis Of Non-Essential Amino Acids

Summary AA Contribution Protein Synthesis

Humans can synthesize 10 of the 20 common amino acids — the Non-essential Amino Acids. The remaining 10 common amino acids — the Essential AMino Acids — must be taken in the diet.

Processes That Contribute Amino Acids
Synthesis Of Non-Essential Amino Acids — The Essential Amino Acids

Summary AA Contribution Non-Essential Amino Acids

Two amino acids that are normally non-essential in healthy adults — arginine and histidine — are not synthesized in sufficient quantities to allow normal growth of children and adolescents and are, therefore, essential for these individuals, and also in some pathological or physiological states when increased protein synthesis is required. All the other common amino acids are non-essential. Lack of a single essential amino acid halts protein synthesis and causes the other excess, unused amino acids to be degraded.

Nitrogen Balance
 

Nitrogen Balance

Nitrogen balance is the difference between the amount of nitrogen taken into the body (mainly as dietary protein) and the amount lost in urine, sweat, feces.

Nitrogen Balance
 

Nitrogen Balance

Healthy adult humans are in nitrogen balance — Zero nitrogen balance: nitrogen intake = nitrogen excreted (mainly as urea in the urine). Positive nitrogen balance: nitrogen intake is greater than nitrogen excreted. Positive nitrogen balance results primarily when new tissue is produced (e.g., during body growth in childhood and adolescence, during pregnancy, and during major wound healing, as after major surgery). Negative nitrogen balance: nitrogen intake is less than nitrogen excreted. Negative nitrogen balance occurs when digestion of body protein exceeds synthesis, and results from several circumstances, e.g., too little dietary protein. too little of one or more of the essential amino acids in the diet, certain hypercatolytic states.

Nitrogen Balance
 

Nitrogen Balance

Major urinary nitrogen excretory products