Conjugated proteins metabolism

The biosynthesis of heme

The biosynthesis of heme occurs in marrow. There are some stages of this process:

1-st one:

Glycine+succinylCoA delta-aminolevulinic acid+CO2+HSCoA (in this reaction the specific B6-dependent decarboxylase participates)

2-nd one:

2 delta-aminolevulinic acidPorphobilinogen (PBG)

3-rd one: 4PBG  Protoporphyrin IX

4-th one: Protoporphyrin IX + Fe  Heme

4 Hemes + Globin (2alfa + 2 beta chains) Hemoglobin

The cleavage of Hemoglobin and formation of pigments of bile, urine and feces

Hemoglobin is a main Protein of erythrocytes. Erythrocytes live 110-120 days. Then they are hemolyzed. Hemoglobin fallen out of erythrocytes and joins with haptoglobin. Such complex is transported to sites of cleavage of hemoglobin (liver and cells of macrophago-monocyte’s system).there haptoglobin is chipped off and hemoglobin beginns to destroy.

This process beginns from oxidative cleavage of methene bridge between first and second pyrrole rings of heme. It results in formation of verdoglobin. Then verdoglobin is broken up to biliverdin, iron and globin. Globin is destroyed as simple proteins to aminoacids and amino acids are broken up by deamination or decarboxylation. Iron exits in blood and binds with beta-globulins forming transferrin. Transferrin transfers iron in liver where it is stored as ferritin. Some of transferrin goe to marrow and there iron is used for biosynthesis of heme. But main substance of cleavage of verdoglobin is biliverdin. This is compound of green color and it is reduced by NADPH2 to undirect bilirubin. Bilirubin is a compound of brown-red color. It is also named non-conjugated (or free), insoluble and toxic.

This bilirubin is undirect because it doesn’t give direct color reaction with reagent Ehrlih. It gives this reaction only after addition of alcohol or coffeine reagent. Alcohol and coffeine reagent precipitate albumins and bilirubin may give color reaction with Ehrlih reagent. It isn’t bound to glucuronic acid therefore it is non-conjugated one. It is insoluble in water, hence it doesn’t transmit through kidneys and appears toxic action on brain.

Undirect bilirubin exits from macrophago-monocyte’s system into blood and there binds with albumins. Albumins prevent organism from its toxic action. Such complex achieves liver and albumins are chipped off. Undirect bilirubin undergoes conjugation with glucuronic acid and direct bilirubin is formed. Therefore it is also named conjugated (non-free one). This bilirubin is soluble in water due to glucuronic acids and may transmit through kidneys in urine, hence it is non-toxic.

Direct bilirubin and some of biliverdin are pigments of bile.

Direct bilirubin exits from liver and in choleductus it is converted to undirect bilirubin due to the chipping off glucuronic acids. Thus undirect bilirubin and some of biliverdin exit in small intestine. Undirect bilirubin is reduced into mesobilinogen (MBG), or urobilinogen (UBG) under influence of microbs of small intestine. A little mojety of MBG exits from small intestine into blood and enters the liver where it is broken up to mono- and dipyrroles (colorless substances) which exit in urine. A main mojety of MBG is converted to stercobilinogen (SBG) in large intestine. Some of SBG goes to kidneys where it is oxidized to stercobilin (pigment of urine). But bulky of SBG is oxidized in large intestine and it is pigment of feces. Some of biliverdin is pigment of feces too.

The color of blood serum depends on the presence of bilirubin. Total bilirubin of blood serum is equal 8-20mcM/L and comprises from undirect (75%) and direct bilirubin (25%).

Jaundices – species, reasons, mechanism, laboratory appearances

The quantity of total bilirubin is increased in some diseases (hyperbilirubinemia). If the level of bilirubin is more than 30mcM/L jaundice of skin and mucosa is appearenced.

There are following species of jaundice:

hemolytic one

mechanical, or obturatory one

hepatic one

Hemolytic jaundice

Causes: 1) paludal fever; 2) blood transfusion; 3) rhesus-conflict etc

Mechanism: increased hemolysis.

Laboratory appearences: The total level of bilirubin is increased due to undirect bilirubin. Color of urine isn’t changed because this kind of bilirubin doesn’t pass through kidneys. The color of feces isn’t changed too or becomes darker due to formation of a big quantity of pigments of feces.

Obturatory jaundice (mechanical one, or choolestasis)

Causes: 1) tumor of head of pancreas; 2) cholecistitis; 3) bile stone disease

Mechanism: cholestasis (obstruction of biliary tract affects efflux of bile)

Laboratory appearances: the total level of bilirubin is increased due to direct bilirubin. Urine is getting dark due to direct bilirubin (beer color). It is due to the direct bilirubin which passes through kidneys. Feces is decolorized because pigments of feces aren’t formed.

Hepatic jaundice:

Causes: 1) hepatitis; 2) cirrhosis

Mechanism: lesion of cells of liver

Laboratory appearences: The total level of bilirubin is increased due to undirect and direct bilirubin. Some hepatic enzymes are determined in blood (AlAt, AsAt etc). Urine is getting dark due to direct bilirubin (beer color). It is due to the direct bilirubin which passes through kidneys. Feces is decolorized because pigments of feces aren’t formed.

The digestion of nucleoproteins and formation of uric acid

The scheme of digestion of nucleoproteins

NPProteins+nucleic acids

Nucleic acidsnucleotides (under action of DNA-se or RNA-se)

Nucleotidesnucleosides (under action of nucleotidases)

Nucleosidesphosphates + nitrogenous bases (under action of nucleosidases)

Purines and pyrimidines are used on biosynthesis of nucleic acids and undergo the deamination. Deamination of them results in formation of ammonia, uric acid (purines catabolism) and beta-alanine, CO2 (pyrimidine catabolism)

The formation of uric acid:

Adenine+H2Ohypoxanthine+NH3

Guanine+H2Oxanthine+NH3

Hypoxanthine+[O] xanthine

Xanthine+[O]uric acid

Clinical correlation of Purine’s metabolism

Hyperuricemia is observed in excessful formation of uric acid, disbalance of elimination of urates and their intake; decrease of urate binding protein (the concentration of them is more than 0.42mM/L). There are primary, secondary and physiological hyperuricemia. Physiological hyperuricemia is developed in uptake of large amount of tomatoes, meat, tea etc.

Primary hyperuricemia is observed in increase of formation of urates or decrease of their elimination. In this case gout (podagra) is developed. Gout is a heterogenic group of derangements of purine’s metabolism in which hyperuricemia, arthritis, deposition of urates in tissues and urolithiasis may be observed. But not all persons with hyperuricemia gout is developed. 85% of persons with hyperuricemia gout isn’t developed. Urates are easy precipitated at temprerature low than +37C, e.g. +32C is temperature of knee joint; +29C temperature of ankle joint; 1-st tarsal-phalanx joint is coldest joint. This joint is often affected in gout (in 80% of cases of gout).

Secondary hyperuricemia is observed in intake of some medicines or in leukemia, Addison’s anemia.

Uric acid increases the mental functions. 40% of geniuses have hyperuricemia. Uric acid and urates carry out antioxidant function instead of ascorbic acid which isn’t synthesized in the body.