Biochemistry - Nutrition and Vitamins Flashcards
What are all the water soluble vitamins?
B1 (thiamine: TPP) B2 (riboflavin: FAD, FMN) B3 (niacin: NAD+) B5 (Pantothenic acid: CoA) B6 (pyridoxine: PLP) B7 (biotin) B9 (folate) B12 (cobalamin) C (ascorbic acid)
All wash out easily from body except B12 and folate (stored in liver).
B-complex deficiencies often result in dermatitis, glossitis, diarrhea.
What is vitamin A and what does it do? And what happens in deficiency and excess?
Vitamin A (retinol) Antioxidant; constituent of visual pigments (retinal). essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells, mucus-secreting cells); prevents squamous metaplasia. Used to treat measles and AML, subtype M3.
Retinol is vitamin A, so think retin-A (used topically for wrinkles and acne). Found in liver and leafy vegetables.
Deficiency: Night blindness (nyctalopia); dry, scaly skin (xerosis cutis); alopecia; corneal degeneration (keratomalacia); immune suppression.
Excess: arthralgias, skin changes (e.g. scaliness), alopecia, cerebral edema, pseudotumor cerebri, osteoporosis, hepatic abnormalities. Teretogenic (cleft palate, cardiac abnormalities) so a neg. pregnancy test and reliable contraception are needed before isotretinoin is prescribed for severe acne.
Note: vitamin A can be found in bear liver so someone who eats it can get toxicity from it
What does B1 do and what happens in deficiency?
In thiamine pyrophosphate (TPP), a cofactor for several dehydrogenase enzyme reactions:
Pyruvate dehydrogenase (links glycolysis to TCA cycle)
alpha-ketoglutarate dehydrogenase (TCA cycle)
Transketolase (HMP shunt)
Branched chain ketoacid dehydrogenase
These enzymes need: Tender Loving Care For Nancy (Thiamine, Lipoate, Coenzyme A, FAD, NAD)
Deficiency: impaired glucose breakdown -> ATP depletion worsened by glucose infusion; highly aerobic tissues (e.g., brain, heart) are affected first.
Wernicke-korsakoff syndrome and beriberi. Seen in malnutrition and malabsorption. Diagnosis made by increase in RBC transketolase activity following B1 administration.
What is Wernicke-korsakoff syndrome and Dry/Web Beri beri?
Wernicke-Korsakoff syndrome: confusion, ophthalmoplegia, ataxia (classic triad for Wernicke encephalopathy). Confabulation, personality changes, memory loss (permanent and is called Korsakoff psychosis). Damage to medial dorsal nucleus of thalamus, mammillary bodies (periventricular hemorrhage). Treat with IV vitamin B1 (thiamine)
Dry beriberi - polyneuritis (peripheral neuropathy), symmetrical muscle wasting.
Wet beriberi - high output cardiac failure (dilated cardiomyopathy), edema.
What is Vitamin B2 and what does it do and what happens in deficiency?
Riboflavin. Component of flavins FAD and FMN, used as cofactors in redox reactions, e.g., the succinate deyhdrogenase reaction in the TCA cycle.
Also important for glutathione reductase (a FAD dependent enzyme and a NADPH dependent).
Deficiency: Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth), Corneal vascularization (red, irritated eyes). (2 Cs of B2). Also glossitis and dermatitis of the genital region.
FAD/FMN are derived from ribflavin (B2 = 2 ATP).
What is Vitamin B3, what does it do, what happens in deficiency/excess?
B3 = niacin. Constituent of NAD+, NADP+ (used in redox reactions). Derived from tryptophan. Synthesis requires Vitamins B2/B6. Used to treat dyslipidemia. lowers levels of VLDL and raises levels of HDL.
Deficiency: Glossitis. Severe deficiency leads to pellagra, which can be caused by Hartnup disease (decreased tryptophan absorption), malignant carcinoid syndrome (increased tyrptophan metabolism), and isoniazid (decreased B6).
Symptoms of pellagra: Diarrhea, Dementia (also hallucinations), Dermatitis (e.g. Casal necklace or hyperpigmentation of sun-exposed limbs).
Excess: Facial flushing (induced by prostalgandin, not histamine), hyperglycemia, hyperuricemia.
What is Vitamin B5 and what happens in deficiency?
Pantothenate
Essential component of coenzyme A (CoA, a cofactor for acyl transfers) and fatty acid synthase. Ex: pyruvate dehydrogenase producing Acetyl CoA and alpha-ketoglutarate dehydrogenase producing Succinyl CoA.
Deficiency: dermatitis, enteritis, alopecia, adrenal insufficiency.
What is Vitamin B6 and what does it do and what happens in deficiency?
pyridoxine
Convert to pyridoxal phosphate, a cofactor used in transamination (e.g. ALT and AST…these are important for converting amino acids and gluneogenic substrates back and forth…alanine to pyruvate and aspartate to oxaloacetate), decarboxylation reactions, glycogen phosphorylase. Synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters including serotonin, epinephrine, norepinephrine, dopamine, and GABA.
Deficiency: Convulsions, hyperirritability, peripheral neuropathy (deficiency inducible by isoniazid and oral contraceptives), sideroblastic anemias due to impaired hemoglobin synthesis and iron excess.
Ex: Dopa to Dopamine by DOPA decarboxylase Tryptophan to Niacin and Serotonin Histidine to Histamine Glycine to porphyrin Glutamate to GABA
What is B7 and what does it do and what happens in deficiency?
Biotin. Cofactor for carboxylation enzymes (which add a 1-carbon group):
Pyruvate carboxylase: pyruvate (3C) to oxaloacetate (4C)
Acetyl-CoA carboxylase: acetyl CoA (2C) to malonyl-CoA (3C).
Propionyl-CoA carboxylase: propionyl-CoA (3C) to methylmalonyl-CoA (4C).
Deficiency: Relatively rare. Dermatitis, alopecia, enteritis. Caused by antibiotic use or excessive ingestion of raw egg whites (they have avidin in the egg whites which binds biotin).
What is B9 and what does it do and what happens in deficiency?
Folic acid.
Converted to tetrahydrofolate, a coenzyme for 1-carbon transfer/methylation reactions.
Important for synthesis of nitrogenous bases in DNA/RNA.
Found in leafy green vegetables and absorbed in jejunum. Small reserve pool in liver.
Deficiency: Macrocytic, megaloblastic anemia; hypersegmented polymorphonuclear cells (PMNs); glossitis; no neurologic symptoms (as opposed to B12 deficiency).
Labs: increased homocysteine, normal methylmalonic acid. Most common vitamin deficiency in the US. Seen in alcoholism and pregnancy.
Deficiency can be caused by several drugs (e.g. phenytoin, sulfonamides, methotrexate). Supplemental maternal folic acid in pregnancy decreases risk of neural tube defects.
What is Vitamin B12 and what does it do and what happens in deficiency?
Cobalamin.
Cofactor for homocysteine methyltransferase (transfers CH3 groups as methylcobalamin) and methylmalonyl-CoA mutase.
Found in animal products. Synthesized only by microorganisms. Very large reserve pool (several years) stored in liver.
Deficiency: Macrocytic, megaloblastic anemia; hypersegmented PMNs; paraethesias and subacute combined degeneration (degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) due to abnormal myelin (Succinyl CoA is used for TCA, myelin, and heme).
Increased homocysteine and methylmalonic acid on labs.
Prolonged deficiency leads to irreversible nerve damage.
Deficiency is usually caused by insufficient intake (e.g. veganism), malabsorption (e.g. sprue, enteritis, Diphyllobothrium latum), lack of intrinsic factor (pernicious anemia, gastric bypass surgery), or absence of terminal ileum (Crohn disease).
Anti-intrinsic factor antibodies diagnostic for pernicious anemia.
What is Vitamin C and what happens in deficiency/excess?
Ascorbic acid.
Antioxidant. Also facilitates iron absorption by reducing it to Fe+2 state.
Necessary for hydroxylation of proline and lysine in collagen synthesis.
Necessary for dopamine B-hydroxylase, which converts dopamine to NE.
Found in fruits and vegetables. Ancillary treatment for methemoglobinemia by reducing Fe+3 to Fe+2.
Deficiency: Scurvy - swollen gums, bruising, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, “corkscrew” hair. Weakened immune response.
Excess: Nausea, vomiting, diarrhea, fatigue, calcium oxalate nephrolithiasis (Vitamin C converted to oxalate). Can increase risk of iron toxicity in predisposed individuals (e.g. those with transfusions, hereditary hemochromatosis).
What is Vitamin D and what happens in deficiency/excess?
D2 = ergocalciferol - ingested from plants.
D3 = cholecalciferol - consumed in milk, formed, in sun-exposed skin (stratum basale).
25-OH D3 = storage form
1,25 - (OH)2 D3 (calcitriol) = active form.
Function: increased intestinal absorption of calcium, phosphate and increased bone mineralization
Deficiency: Rickets in children (bone pain and deformity), osteomalacia in adults (bone pain and muscle weakness), hypocalcemic tetany. Breastfed infants should receive oral vitamin D. Deficiency is exacerbated by low sun exposure, pigmented skin, prematurity. Can be caused by liver disease (also by inducing cytochrome P450 in the smooth endoplasmic reticulum which causes smooth-ER hyperplasia…metabolizes enzymes that are also there like 25-hydroxylase and causes decreased activity…this can also happen and cause increased metabolism of estrogen/progresterone in pregnancy pills and causes failure of birth control pills causing pregnancy. gamma-glutyltransferase will also be increased because it’s in the smooth-ER and is why this can be used for alcoholism diagnosis). Renal disease also can cause deficiency (diabetes mellitus is the most common cause of chronic renal failure). Need to put them on 1,25 vitamin D (note that over the counter is D3 form).
Excess: Hypercalcemia, hypercalcuria, loss of appetite, stupor. Seen in sarcoidosis (increased activation of vitamin D by epithelioid macrophages).
What is Vitamin E and what happens in deficiency?
Tocopherol/tocotrienol.
Anti-oxidant (protects erythrocytes and membranes from free radical damage and keeping oxidized LDL off). Also important for myelin. E is for erythrocytes. Can enhance the anticoagulant effects of warfarin.
Deficiency: hemolytic anemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract demyelination.
Toxicity: Inhibits the Vitamin K coagulation factors and you become anticoagulated.
Can have neurological presentation similar to B12 deficiency but without megaloblastic anemia, hypersegmented neutrophils, or increased serum methylmalonic acid levels.
What is vitamin K and what happens in deficiency?
Cofactor for gamma-carboxylation of glutamic acid residues on various proteins required for blood clotting. Synthesized by intestinal flora.
K is for Koagulation. Necessary for the activation of clotting factors II, VII, IX, X, and proteins C/S. Warfarin - vit K antagonist.
Note: K2 is inactive form and K1 is active form. Epoxide reductase (which is the enzyme that Warfarin blocks) takes K2 and makes K1. Gamma carboxylation on prolines and lysines are needed for binding Calcium in clots.
Also warfarin is rat poison so digesting it makes you anti-coagulated.
Deficiency: Neonatal hemorrhages with increased PT and PTT but normal bleeding time (neonates have sterile intestines and are unable to synthesize vitamin K). Can also occur after prolonged use of broad spectrum antibiotics.
Not in breast milk; neonates are given vitamin K injection at birth to prevent bleeding diathesis.
