Biochemistry: Vitamins and Minerals
1. Vitamins: small, low molecular weight, organic mols required for normal function, most we don't synthesize, classified as fat or water soluble.
Which vitamins are derived from isopentenyl pyrophosphate? Vitamin A (terpene), D, E, K, cholesterol
2. Roles of vitamins and minerals in metabolism: precursors or cofactors for enzymes
3. Deficiencies due to: inadequate diet, inadequate absorbtion, inadequate use, increased requirements, increased excretion, loss of microbial synthesis, drug induced
4. What is the biochemical role of each of the water-soluble vitamins? Identify metabolic pathways for which each is important. What are the active forms of each water-soluble vitamin?
C=ascorbic acid--antioxidant, cofactor, imp in re-activing vit E, manufacture carnitine, incr Fe2+ intake, synthesis of catecholamines, hydroxylation of proline & lysine to make collagen, conversion of chol to bile acid, we can't make it but many critters can, deficiency-->scurvy
B1=thiamine--carbonyl transfers (2x in pentose pathway, transketolase) and decarboxylation, PDH complex (forms acetyl CoA btw glycolysis & krebs), alpha-KGDH (Krebs), BCAADH (degrade branched chain aa's val, leu, iso), not stored but is concentrated in muscle tissue, deficiency-->beriberi, alcoholics-->transketolase problem-->Wernicke-Korsakoff syndrome
B2=Riboflavin--synthesis of FAD (liver) and FMN (intest mucosa) (active forms), single e- transfers, forms covalent bond to enz to prevent ox damage, light sensitive, in ETC, limited manufacture from gut bugs, easily absorbed from milk, cheese, leafy green vegetables, liver, legumes, yeast and almonds, stored in liver, subclinical deficiency common esp in females on BC pills,
B3=Niacin==>nicotinamide (anti-inflam), nicotinic acid (vasodilator, gastrointestinal, hepatic, and hypolipemic)--precursor of NAD+, NADH, NAD and NADP+ (active forms), used 3x in Krebs cycle (1. 2&3. isocit-->alphaKG-->suc CoA), coenzymes in redox, can be synthesized from aa: tryptophan (inefficient), corn is deficient, deficiency-->pellagra, 4D's: dermatitis, diarrhea, dementia, death, also very toxic at high levels, not stored, involved with detoxification of xenochemicals, DNA repair, and production of steroid hormones in the adrenal gland.
Biotin=B7=Vitamin H--Biotin is a cofactor in the metabolism of fatty acids and leucine, and in gluconeogenesis. Coenzyme in carboxylation (carries CO2) (gluconeo: pyruvate-->OAA, propionic a-->methymalonyl CoA, also fa syn: malonyl CoA-->?), 1/2 of our requirements come from gut bugs (antibiotics bad), absorbed in jejunum made in colon, links to lysine on enyzme, EGG white protein avidin binds biotin, destroyed in cooking, deficiency-->priopionic acidemia, decreased gluconeogenesis. People with type 2 DIABETES often have low levels of biotin. Biotin may be involved in the synthesis and release of insulin. Preliminary studies in both animals and people suggest that biotin may help improve blood sugar control in those with diabetes, particularly type 2 diabetes. No science backs up hair growth claims, but does seem to help kids with PKU. Don't eat lots of raw egg whites.
Pantothenic acid=B5--constituent of CoA (active), acyl group carrier, gut bugs make some, used in chol biosyn, Krebs, pyruvate ox, fa syn (long arm) & degrade. (NOT in glycolysis). Best dietary sources: whole-grains & eggs. deficiency ex rare-->paresthesia. unstable: not stored.???
Folic acid--1 carbon transfers (methyl cycle), storage in bod lasts 4-6 mo, lack in preg causes megoblastic anemia, absorbed as monoglutamate but exists in cells as polyglutamate
B12=cobalamin--heme synthesis, use of propionyl CoA (odd fa chain anabolism) and methylation of homocysteine to methionine, cyanide can replace cobalt in corrin ring?, absorbed in ileum w/ intrinsic factor from gastric mucosa, stored in liver, depletes in 6-8 years, deficiency-->pernicious anemia.
Pryidoxine=B6--amino acid metabolism (transamination, decarbox, deaminate, racemize), this form in supplements, some gut bug syn, absorbed in upper GI, convert to PLP in liver, brain, kidney, deficiency-->limits heme syn (1st step can't add succCoA & glycine to make delta-amino-levulinic acid-->sideroblastic anemia (similar to iron deficiency anemia but w/ normal serum iron), meds that decrease B6 incl: isoniazid (for TB) and penicillamine (for lead)
Pyridoxal phosphate=PLP--active circulating form of B6, , some gut bug syn
Pryidoxamine--active circulating form of B6, some gut bug syn
5. Which vitamins can be synthesized by humans? One form of D in the skin with UV, from dietary precursors: vitamin A from beta carotene, niacin from tryptophan.
Which vitamins are supplied by intestinal bacteria? Vit K and biotin (B7)
6. Characterize the best understood functions of vitamins A, D, E, K. ALL FAT SOLUBLE.
Vit A=retinal (active), retinol (active) and retinoic acid (lipid-sol hormone in bone metabolism), imp in cell differentiation, bone metabolism, converting cholesterol to vit D, 90% stored in liver as retinol esters (retinyl palmitate), intestine converts carotenoids (beta carotene) to retinol (we synthesize vit A), deficiency-->epithelial cells that should have bene cuboidal, columnar or goblet are squamous, eye lens cells become keratinized-->cataracts
Vit D=cholecalciferol is active D3, imp in bone metabolism, mobilizing Ca++, syn in skin w/ UV, melanin absorbs in same wavelength, hydroxylated in liver, activated to 1, 25 form in kidney, becomes sterol hormone that can diffuse through membranes, bile is required for absorbtion in GI, not stored: short halflife.
Vit E=alpha-tocopherol and others--unmetabolized in the body, prevents free radical formation in polyunsaturated fa's, bile required for absorbtion, we don't make it
Vit K--imp in synthesis of blood clotting factors, cofactor in carboxylation of clot factors, plant form = phylloquinones, bile required for absorbtion, supplied by gut bugs
7. Which vitamins are stored and where?
A--90% in liver
B1--not stored, concentrated in muscle
B2--stored in liver
B3--not stored, can synthesize from tryptophan, toxic in high doses
B5--not stored (pantothenic)
B7--not stored
8. What is the bioactive form of vitamin D? 1, 25-dihydroxycholecalciferol, aka 1, 25-(OH)2D3. Where is this form synthesized? in the kidney. What role is played by ultraviolet light in vit D synthesis? UV light converts 7-dehydrocholesterol to cholecalciferol in the skin. Cholecalciferol is converted to 25-hydroxycholecalciferol in the liver. These two forms have half lives of about 30 days, and are the form that is stored longest. Once activated the 1, 25 hihydroxy form has a half life of about 4 hours.
9. Identify enzymes and processes associated with each of the following trace elements: copper, zinc, molybdenum, selenium, cobals, manganese.
COPPER: cytochrome oxidase, ceruloplasmin, dopamine beta-hydroxylase, tyrosinase, cytosolic SOD
ZINC: carbonic anhydrase, cytosolic SOD, carboxypeptidase
MOLYBDENUM: xanthine oxidase
SELENIUM: glutathione peroxidase, (antioxidant)
COBALT: vitamin B12, heme synthesis and synthesis and maintenance of myelin
MANGANESE: pyruvate carboxylase, mitochondrial SOD
ISOPENTENYL PYROPHOSPHATE (IPP) is an intermediate in the classical, HMG-CoA reductase pathway used by organisms in the biosynthesis of terpenes and terpenoids. IPP is formed from acetyl-CoA via mevalonic acid. IPP can then be isomerized to dimethylallyl pyrophosphate by the enzyme isopentenyl pyrophosphate isomerase.
TERPENES are a large and varied class of hydrocarbons, produced primarily by a wide variety of plants, particularly conifers, though also by some insects such as swallowtail butterflies, which emit terpenes from their osmeterium. They are the major components of resin, and of turpentine produced from resin. The name "terpene" is derived from the word "turpentine".
In addition to their roles as end-products in many organisms, terpenes are major biosynthetic building blocks within nearly every living creature. Steroids, for example, are derivatives of the triterpene squalene.
When TERPENES are modified chemically, such as by oxidation or rearrangement of the carbon skeleton, the resulting compounds are generally referred to as terpenoids. Some authors will use the term terpene to include all terpenoids. Terpenoids are also known as Isoprenoids.
Terpenes and terpenoids are the primary constituents of the essential oils of many types of plants and flowers. Essential oils are used widely as natural flavor additives for food, as fragrances in perfumery, and in traditional and alternative medicines such as aromatherapy. Synthetic variations and derivatives of natural terpenes and terpenoids also greatly expand the variety of aromas used in perfumery and flavors used in food additives. Vitamin A is an example of a terpene.
The TERPENOIDS, sometimes referred to as isoprenoids, are a large and diverse class of naturally-occurring organic chemicals similar to terpenes, derived from five-carbon isoprene units assembled and modified in thousands of ways. Most are multicyclic structures that differ from one another not only in functional groups but also in their basic carbon skeletons. These lipids can be found in all classes of living things, and are the largest group of natural products.
PLANT TERPENOIDS are used extensively for their aromatic qualities. They play a role in traditional herbal remedies and are under investigation for antibacterial, antineoplastic, and other pharmaceutical functions. Terpenoids contribute to the scent of eucalyptus, the flavors of cinnamon, cloves, and ginger, and the color of yellow flowers. Well-known terpenoids include citral, menthol, camphor, Salvinorin A in the plant Salvia divinorum, and the cannabinoids found in Cannabis.
The steroids and sterols in animals are biologically produced from terpenoid precursors. Sometimes terpenoids are added to proteins, e.g., to enhance their attachment to the cell membrane; this is known as isoprenylation.
Many of these are substrates for plant Cytochrome P450.
Which vitamins are derived from isopentenyl pyrophosphate? Vitamin A (terpene), D, E, K, cholesterol
2. Roles of vitamins and minerals in metabolism: precursors or cofactors for enzymes
3. Deficiencies due to: inadequate diet, inadequate absorbtion, inadequate use, increased requirements, increased excretion, loss of microbial synthesis, drug induced
4. What is the biochemical role of each of the water-soluble vitamins? Identify metabolic pathways for which each is important. What are the active forms of each water-soluble vitamin?
C=ascorbic acid--antioxidant, cofactor, imp in re-activing vit E, manufacture carnitine, incr Fe2+ intake, synthesis of catecholamines, hydroxylation of proline & lysine to make collagen, conversion of chol to bile acid, we can't make it but many critters can, deficiency-->scurvy
B1=thiamine--carbonyl transfers (2x in pentose pathway, transketolase) and decarboxylation, PDH complex (forms acetyl CoA btw glycolysis & krebs), alpha-KGDH (Krebs), BCAADH (degrade branched chain aa's val, leu, iso), not stored but is concentrated in muscle tissue, deficiency-->beriberi, alcoholics-->transketolase problem-->Wernicke-Korsakoff syndrome
B2=Riboflavin--synthesis of FAD (liver) and FMN (intest mucosa) (active forms), single e- transfers, forms covalent bond to enz to prevent ox damage, light sensitive, in ETC, limited manufacture from gut bugs, easily absorbed from milk, cheese, leafy green vegetables, liver, legumes, yeast and almonds, stored in liver, subclinical deficiency common esp in females on BC pills,
B3=Niacin==>nicotinamide (anti-inflam), nicotinic acid (vasodilator, gastrointestinal, hepatic, and hypolipemic)--precursor of NAD+, NADH, NAD and NADP+ (active forms), used 3x in Krebs cycle (1. 2&3. isocit-->alphaKG-->suc CoA), coenzymes in redox, can be synthesized from aa: tryptophan (inefficient), corn is deficient, deficiency-->pellagra, 4D's: dermatitis, diarrhea, dementia, death, also very toxic at high levels, not stored, involved with detoxification of xenochemicals, DNA repair, and production of steroid hormones in the adrenal gland.
Biotin=B7=Vitamin H--Biotin is a cofactor in the metabolism of fatty acids and leucine, and in gluconeogenesis. Coenzyme in carboxylation (carries CO2) (gluconeo: pyruvate-->OAA, propionic a-->methymalonyl CoA, also fa syn: malonyl CoA-->?), 1/2 of our requirements come from gut bugs (antibiotics bad), absorbed in jejunum made in colon, links to lysine on enyzme, EGG white protein avidin binds biotin, destroyed in cooking, deficiency-->priopionic acidemia, decreased gluconeogenesis. People with type 2 DIABETES often have low levels of biotin. Biotin may be involved in the synthesis and release of insulin. Preliminary studies in both animals and people suggest that biotin may help improve blood sugar control in those with diabetes, particularly type 2 diabetes. No science backs up hair growth claims, but does seem to help kids with PKU. Don't eat lots of raw egg whites.
Pantothenic acid=B5--constituent of CoA (active), acyl group carrier, gut bugs make some, used in chol biosyn, Krebs, pyruvate ox, fa syn (long arm) & degrade. (NOT in glycolysis). Best dietary sources: whole-grains & eggs. deficiency ex rare-->paresthesia. unstable: not stored.???
Folic acid--1 carbon transfers (methyl cycle), storage in bod lasts 4-6 mo, lack in preg causes megoblastic anemia, absorbed as monoglutamate but exists in cells as polyglutamate
B12=cobalamin--heme synthesis, use of propionyl CoA (odd fa chain anabolism) and methylation of homocysteine to methionine, cyanide can replace cobalt in corrin ring?, absorbed in ileum w/ intrinsic factor from gastric mucosa, stored in liver, depletes in 6-8 years, deficiency-->pernicious anemia.
Pryidoxine=B6--amino acid metabolism (transamination, decarbox, deaminate, racemize), this form in supplements, some gut bug syn, absorbed in upper GI, convert to PLP in liver, brain, kidney, deficiency-->limits heme syn (1st step can't add succCoA & glycine to make delta-amino-levulinic acid-->sideroblastic anemia (similar to iron deficiency anemia but w/ normal serum iron), meds that decrease B6 incl: isoniazid (for TB) and penicillamine (for lead)
Pyridoxal phosphate=PLP--active circulating form of B6, , some gut bug syn
Pryidoxamine--active circulating form of B6, some gut bug syn
5. Which vitamins can be synthesized by humans? One form of D in the skin with UV, from dietary precursors: vitamin A from beta carotene, niacin from tryptophan.
Which vitamins are supplied by intestinal bacteria? Vit K and biotin (B7)
6. Characterize the best understood functions of vitamins A, D, E, K. ALL FAT SOLUBLE.
Vit A=retinal (active), retinol (active) and retinoic acid (lipid-sol hormone in bone metabolism), imp in cell differentiation, bone metabolism, converting cholesterol to vit D, 90% stored in liver as retinol esters (retinyl palmitate), intestine converts carotenoids (beta carotene) to retinol (we synthesize vit A), deficiency-->epithelial cells that should have bene cuboidal, columnar or goblet are squamous, eye lens cells become keratinized-->cataracts
Vit D=cholecalciferol is active D3, imp in bone metabolism, mobilizing Ca++, syn in skin w/ UV, melanin absorbs in same wavelength, hydroxylated in liver, activated to 1, 25 form in kidney, becomes sterol hormone that can diffuse through membranes, bile is required for absorbtion in GI, not stored: short halflife.
Vit E=alpha-tocopherol and others--unmetabolized in the body, prevents free radical formation in polyunsaturated fa's, bile required for absorbtion, we don't make it
Vit K--imp in synthesis of blood clotting factors, cofactor in carboxylation of clot factors, plant form = phylloquinones, bile required for absorbtion, supplied by gut bugs
7. Which vitamins are stored and where?
A--90% in liver
B1--not stored, concentrated in muscle
B2--stored in liver
B3--not stored, can synthesize from tryptophan, toxic in high doses
B5--not stored (pantothenic)
B7--not stored
8. What is the bioactive form of vitamin D? 1, 25-dihydroxycholecalciferol, aka 1, 25-(OH)2D3. Where is this form synthesized? in the kidney. What role is played by ultraviolet light in vit D synthesis? UV light converts 7-dehydrocholesterol to cholecalciferol in the skin. Cholecalciferol is converted to 25-hydroxycholecalciferol in the liver. These two forms have half lives of about 30 days, and are the form that is stored longest. Once activated the 1, 25 hihydroxy form has a half life of about 4 hours.
9. Identify enzymes and processes associated with each of the following trace elements: copper, zinc, molybdenum, selenium, cobals, manganese.
COPPER: cytochrome oxidase, ceruloplasmin, dopamine beta-hydroxylase, tyrosinase, cytosolic SOD
ZINC: carbonic anhydrase, cytosolic SOD, carboxypeptidase
MOLYBDENUM: xanthine oxidase
SELENIUM: glutathione peroxidase, (antioxidant)
COBALT: vitamin B12, heme synthesis and synthesis and maintenance of myelin
MANGANESE: pyruvate carboxylase, mitochondrial SOD
ISOPENTENYL PYROPHOSPHATE (IPP) is an intermediate in the classical, HMG-CoA reductase pathway used by organisms in the biosynthesis of terpenes and terpenoids. IPP is formed from acetyl-CoA via mevalonic acid. IPP can then be isomerized to dimethylallyl pyrophosphate by the enzyme isopentenyl pyrophosphate isomerase.
TERPENES are a large and varied class of hydrocarbons, produced primarily by a wide variety of plants, particularly conifers, though also by some insects such as swallowtail butterflies, which emit terpenes from their osmeterium. They are the major components of resin, and of turpentine produced from resin. The name "terpene" is derived from the word "turpentine".
In addition to their roles as end-products in many organisms, terpenes are major biosynthetic building blocks within nearly every living creature. Steroids, for example, are derivatives of the triterpene squalene.
When TERPENES are modified chemically, such as by oxidation or rearrangement of the carbon skeleton, the resulting compounds are generally referred to as terpenoids. Some authors will use the term terpene to include all terpenoids. Terpenoids are also known as Isoprenoids.
Terpenes and terpenoids are the primary constituents of the essential oils of many types of plants and flowers. Essential oils are used widely as natural flavor additives for food, as fragrances in perfumery, and in traditional and alternative medicines such as aromatherapy. Synthetic variations and derivatives of natural terpenes and terpenoids also greatly expand the variety of aromas used in perfumery and flavors used in food additives. Vitamin A is an example of a terpene.
The TERPENOIDS, sometimes referred to as isoprenoids, are a large and diverse class of naturally-occurring organic chemicals similar to terpenes, derived from five-carbon isoprene units assembled and modified in thousands of ways. Most are multicyclic structures that differ from one another not only in functional groups but also in their basic carbon skeletons. These lipids can be found in all classes of living things, and are the largest group of natural products.
PLANT TERPENOIDS are used extensively for their aromatic qualities. They play a role in traditional herbal remedies and are under investigation for antibacterial, antineoplastic, and other pharmaceutical functions. Terpenoids contribute to the scent of eucalyptus, the flavors of cinnamon, cloves, and ginger, and the color of yellow flowers. Well-known terpenoids include citral, menthol, camphor, Salvinorin A in the plant Salvia divinorum, and the cannabinoids found in Cannabis.
The steroids and sterols in animals are biologically produced from terpenoid precursors. Sometimes terpenoids are added to proteins, e.g., to enhance their attachment to the cell membrane; this is known as isoprenylation.
Many of these are substrates for plant Cytochrome P450.