7. Metabolism of tryptophan.

Tryptophan is an essential amino acid. The main way of tryptophan metabolism leads to the synthesis of NAD⁺, reducing the need for vitamin PP. The lack of tryptophan in humans leads to a decrease in body weight, and in the case of the newborn, even a 10-day shortage of tryptophan leads to anorexia and hypoproteinemia.

Hartnup’s disease is associated with congenital malabsorption of tryptophan in the intestine and reabsorption of tryptophan and products of its metabolism in the kidney. The main manifestations are pellagra-like skin lesions, mental disorders, hyperaminoaciduria.

2.6. Metabolism of conjugated proteins. Chromoproteins metabolism

The human body contains 4.5-5.0 g of iron. The share of hemoglobin accounts for 60-70%. Changes in the synthesis or degradation of porphyrins and their complexes with proteins lead to disruption of vital functions and the development of diseases.

By using iron containing conjugative proteins in food, iron releases from complexes with proteins in the intestine and is absorbed in the form of divalent ions. Transport of iron to sites of hematopoiesis occurs in the transferrin (a glycoprotein of blood plasma). Iron combines with the protein apoferritin to form ferritin in the cells. The function of ferritin is iron storage. Most of ferritin is in the liver, spleen and bone marrow. In conjugated proteins iron is in the trivalent state.

Excess iron is not absorbed. The need for iron increases in various anemias. After digestion heme undergoes oxidation to hematin. Hematin is not absorbed in the intestine. It is excreted in unchanged form or decomposes under the action of the enzymes of the intestinal microflora.

The degradation of hemoglobin in the tissues (the formation of bile pigments)

The life span of erythrocytes is 120 days. The destruction of erythrocytes and hemoglobin degradation occur in the liver, spleen and bone marrow. The degradation of hemoglobin begins with cleavage of methylen bridge between the 1st and 2nd cycles of the porphyrin ring under the action of NADP-containing heme oxygenase. Further degradation occurs spontaneously. Biliverdin (a green pigment), CO and Fe³⁺ are formed.

Hemoglobin verdoglobin 

(green pigment)

 biliverdin (bile pigment) Bilirubin

iron

globin

Bilirubin

Then bilirubin reductase reduces it to form bilirubin (a yellow pigment). Bilirubin is formed in the liver, spleen, and, apparently, erythrocytes. It enters the liver and then with the bile in the gall bladder.

Free or indirect bilirubin is insoluble in water and transported in a bond form to proteins of blood plasma. Protein pre-sedimentation with alcohol requires determining its concentration in the blood by the Ehrlich diazoreagent. The content of bilirubin in the blood is 15 micromoles per liter; about 75% is indirect bilirubin. Increasing of its concentration to 35 mmol/l leads to jaundice, an even higher level leads to severe poisoning. In the liver indirect bilirubin is neutralized by binding to UDP-glucuronic acid by the enzyme bilirubin glucuronyltransferase. Bilirubin diglucuronide is formed. It is direct bilirubin, or conjugated bilirubin. It is water soluble and gives a direct reaction with diazoreagent.

Conjugated bilirubin is always present in the bile. Direct and indirect bilirubin concentrations, as well as the relation between them in the blood is changing sharply at lesions of the liver, spleen, bone marrow, blood diseases, etc. Determination of both forms of bilirubin in the blood is important in the diagnosis of various forms of jaundice. Indirect bilirubin is found in the gallstones.

Bilirubin diglucoronide splits in the intestine by the bacteria. Bilirubin is reduced to mesobilinogen (urobilinogen, colorless), urobilin, stercobilinogen and stercobilin (brown). The main part of them are excreted in the feces (approximately 300 mg/day), about 5% is absorbed into the blood, then enter the bile or excreted in the urine (4 mg/day). Conversion of urobilin to urobilinogen takes place in light. Urobilinogen is colorless and urobilin is yellow. That is why the rich urobilin urine darkens with time.

A small amount of urobilinogen is absorbed, and then passes through the portal vein to the liver and where it is broken. Elevated level of urobilinogen in the urine is the evidence of liver disease (hepatic or hemolytic jaundice). Lack of sterkobilinogen in urine in the presence of bilirubin and biliverdin is the evidence of complete cessation of the flow bile into the intestines (blockage of the gallbladder duct or common bile duct (gallstone disease, cancerous lesions of the pancreas, etc.)).