Chapter 21 Enzymes and Vitamins

1. Chapter 21 Enzymes and Vitamins 21.8 Vitamins and Coenzymes

2. Function of Coenzymes • A coenzyme prepares the active site for catalytic activity.

3. Water-Soluble Vitamins Water-soluble vitamins are: • Soluble in aqueous solutions. • Used as cofactors by many enzymes. • Not stored in the body.

4. Fat-Soluble Vitamins Fat-soluble vitamins: • Are A, D, E, and K. • Soluble in lipids, but not in aqueous solutions. • Important in vision, bone formation, antioxidants, and blood clotting. • Stored in the body.

5. Thiamin (Vitamin B1) Thiamin: • Was the first B vitamin identified. • Is part of the coenzyme thiamin pyrophosphate. • TPP coenzyme is required by enzymes in the decarboxylation of -keto carboxylic acids. • Deficiency results in beriberi (fatigue, weight loss, and nerve degeneration).

6. Riboflavin (Vitamin B2) Riboflavin is: • Made of the sugar alcohol ribitol and flavin. • Part of the coenzymes flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). • Needed for good vision and healthy skin.

7. Niacin (Vitamin B3) Niacin: • Is part of the coenzyme nicotinamide adenine dinucleotide (NAD+) involved in oxidation-reduction reactions. • Deficiency can result in dermatitis, muscle fatigue, and loss of appetite. • Is found in meats, rice, and whole grains.

8. Pantothenic Acid (Vitamin B5) Pantothenic acid: • Is part of coenzyme A needed for energy production as well as glucose and cholesterol synthesis. • Deficiency can result in fatigue, retarded growth, cramps, and anemia. • Is found in salmon, meat, eggs, whole grains, and vegetables.

9. Pyridoxine (Vitamin B6) • Pyridoxine and pyridoxal are two forms of vitamin B6, which are converted to the coenzyme pyridoxal phosphate (PLP). • PLP is required in the transamination of amino acids and decarboxylation of carboxylic acids. • Deficiency of pyridoxine may lead to dermatitis, fatigue, and anemia.

10. Cobalamin (Vitamin B12) Cobalamin: • Consists of four pyrrole rings with a Co2+. • Is a coenzyme for enzymes that transfer methyl groups and produce red blood cells. • Deficiency can lead to pernicious anemia and nerve damage.

11. Ascorbic Acid (Vitamin C) Vitamin C: • Is required in collagen synthesis. • Deficiency can lead to weakened connective tissue, slow-healing wounds, and anemia. • Is found in blueberries, citrus fruits, tomatoes, broccoli, red and green vegetables.

12. Folic Acid (Folate) Folic acid (folate): • Consists of pyrimidine, p-aminobenzoic acid, and glutamate. • Forms the coenzyme THF (tetrahydrofolate) used in the transfer of carbon groups and the synthesis of nucleic acids. • Deficiency can lead to abnormal red blood cells, anemia, and poor growth.

13. Vitamin A • Vitamin A is obtained from meats and beta-carotenes in plants. • Beta-carotenes are converted by liver enzymes to vitamin A (retinol).

14. Vitamin D Vitamin D (D3): • Is synthesized in skin exposed to sunlight. • Regulates the absorption of phosphorus and calcium during bone growth. • Deficiency can result in weakened bones. • Sources include cod liver oil, egg yolk, and enriched milk.

15. Vitamin E Vitamin E: • Is an antioxidant in cells. • May prevent the oxidation of unsaturated fatty acids. • Is found in vegetable oils, whole grains, and vegetables.

16. Vitamin K • Vitamin K1 in plants has a saturated side chain. • Vitamin K2 in animals has a long unsaturated side chain. • Vitamin K2 is needed for the synthesis of zymogens for blood clotting. 3 n

17. Clinical ExampleCase Study: Hepatitis • A 36-year old man was admitted to a hospital following episodes of nausea, vomiting, and general malaise. • His urine was darker than usual. • Upon examination it was discovered that his liver was enlarged and tender to palpation. • Liver function tests were abnormal; plasma ALT was 1500 IU/L (Alanine aminotransferase 6.0 – 21 U/L); AST was 400 IU/L (Aspartate aminotransferase 7.0 – 20 U/L). • During the next 24 hours the man developed jaundice, and his plasma total bilirubin was 9.0 mg/dL (0.2 – 1 mg/dL). • A diagnosis of hepatitis was made.

18. Biochemical Questions: • What reactions are catalyzed by AST and ALT? What is the coenzyme? • What conditions are important to maintain in performing the enzyme assays? • Which other enzymes might have been elevated in the plasma? • How does “total” bilirubin relate to “direct” and “indirect” bilirubin?

19. Case discussion: Hepatitis is an inflammation of the liver. • Transaminases (amino acids metabolism) • Catalyze the transfer of α-amino groups from amino acid to a α-keto acid through the intermediary coenzyme pyridoxal phosphate (derived from the B6 vitamin, pyridoxine) • Amino acids enter into the Krebs cycle for oxidation to CO2 and H2O • Amino acid1 + keto acid2 ↔ amino acid 2 + keto acid1 (pyridoxal phosphate ↔ pyridoxamine phosphate) slide 11 ALT and AST

20. 2. Temperature and pH • Excessive shaking and elevated temp should be avoided • Anticoagulants shouldn't inhibit the assays • Hemolysis should be avoided in order not to release enzymes of the blood cells

21. 3. Other enzymes that could be elevated: • A number of proteins may leak from cell into plasma, such as other transaminases and LD can be elevated in liver diseases • AST and ALT high levels occurs before jaundice is noted • There is poor correlation of enzyme activity with severity of the disease

22. 4. Bilirubin • Biliribin is derived from the breaking down of the hemoglobin of aging red blood cells • Bilirubin is insoluble in water; to be excreted it is converted to a water-soluble bilirubin diglucuronide in the liver • The first formed “indirect” bilirubin is bound to albumin and rapidly transported in plasma to the liver; albumin is not taken into the liver cells • “Direct” bilirubin (water soluble) is secreted into the bile canaliculus, together with other bile constituents and is collected in the gallbladder • Some of the bile pigments are excreted in the feces and some water soluble bilirubin (not free bilirubin) is excreted by the kidney into the urine

23. Bilirubin continue: • In hepatitis, the formation of water soluble bilirubin is less efficient • The secretion of “direct” bilirubin (water soluble bilirubin) into the bile canaliculi is impaired • The result is a backing-up of the bilirubin excretion with a build-up of total bilirubin in the blood. • The initial increase is expressed as a darkened urine, followed by jaundice