Biochemistry- Vitamins Flashcards
List the fat soluble vitamins
ADEK
List the Water Soluble vitamins
B1, B2, B3, B5, B6, B7, B9, B12, C
What are two primary sources of vitamin A ?
Liver and leafy vegetables
What is the function of Vitamin A?
Antioxidant, essential for normal differentiation of epithelial cells into specialized tissue, retinal pigment
What does Vitamin A prevent?
Squamous metaplasia
What conditions is Vitamin A used to treat
oral for cystic acne
All-trans retinoic acid for AML subtype M3
Measles
What issues does deficiency in vitamin A cause?
Night blindness, scaly and dry skin, corneal degeneration, bitot spots on conjunctiva, immunosuppression
Acute toxicity of excess Vitamin A
Nausea, vomiting, vertigo and blurry vision
Chronic toxicity of excess vitamin A
Alopecia, scaly skin, hepatomegaly, arthralgia, pseudotumor cerebri
Why must a patient take two types of birth control and have a negative pregnancy test before taking vitamin A?
it’s a teratogen (cleft palate, cardiac abnormalities)
What is ergocalciferol
Vitamin D2, derived from plants
What is cholecalciferol
Vitamin D3, derived from milk and sun-exposed skin (stratum basale)
What is the active form of Vitamin D?
1,25 (OH) D3 aka calcitriol. Synthesized by 1 alpha hydroxylase in the liver
What does a deficiency in 1 alpha hydroxylase result in?
Rickets type 1 (AR)
What is the function of vitamin D?
Increase absorption of calcium and phosphate in the intestines, increase bone mineralization at low levels and increase bone resorption at high levels
What does a deficiency of Vit D lead to?
Rickets in children, osteomalacia in adults. Breastfed babies need supplemental Vitamin D
What does an excess of Vitamin D lead to?
Hypercalcemia, hypercalciura, loss of appetite, stupor
How does granulomatous disease lead to excess vitamin D?
Increased activation by macrophages
What is the function of Vitamin E (tocopherol, tocotrienol)?
Antioxidant that protects RBCs and membranes from oxidative damage
What are consequences of Vitamin E deficiency?
Hemolytic anemia, acanthocytes on histology, posterior column and spinocerebellar tract demyelination
How is Vitamin E deficiency different from Vitamin B12 deficiency?
no megaloblastic anemia, no hypersegmented neutrophils, no elevation in serum methylmalonic acid
Which vitamin enhances the anticoagulation effect of warfarinV
Vitamin E
What is the function of Vitamin K
“K”oagulation; cofactor for gamma carboxylation of Glutamate residue of clotting proteins 2, 7, 9, 10 C and S.
What two scenarios have Vitamin K deficiency?
Neonates (sterile intestines)
Prolonged use of broad-spectrum antibiotics (killing intestinal flora)
What is the name if Vitamin B1
Thiamine
What is the function of Thiamine
TPP cofactor for most dehydrogenase enzymes in ATP-generating (glucose utilization) reactions
for which enzymes is Thiamine a cofactor
alpha-ketoglutarate dehydrogenase
Transketolase
Pyruvate dehydrogenase
Branched-chain ketoacid dehydrogenase
How is B1 deficiency diagnosed?
Increased RBC transketolase activity after B1 infusion
What vitamin is Wernicke-Korsakoff a deficiency in?
Thiamine B1
What is the classic triad presentation of Wernicke-Korsakoff
Confusion, ophthalmoplegia, ataxia (+ personality change, permanent memory loss, confabulation)
What is damaged in Wernicke-Korsakoff?
Medial dorsal nucleus of thalamus, mammilary bodies
What is wet beriberi?
Dilated cardiomyopathy and edema due to B1 deficiency
What is dry beriberi?
Polyneuritis and symmetrical muscle wasting due to B1 deficiency
Sources of thiamine?
Beef, legumes, liver, milk
Which vitamin is Riboflavin?
B2
What is the function of B2?
Cofactor FAD, FMN in succinate dehydrogenase reaction of TCA cycle (2ATP generation)
What are the consequences of B2 deficiency?
Cheilosis (lip thickening and fissures around corners) and corneal vascularization
Which vitamin is Niacin
B3
Where is Niacin derived from?
Tryptophan
Which cofactors is Niacin part of
NAD, NADP
Which two vitamins are required for the synthesis of B3?
B2 and B6
What clinical issue is B3 used to correct?
Dyslipidemia (lowers VLDL, increases HDL)
What are the 3Ds of B3 deficiency (pellagra)
Dementia
Diarrhea
Dermatitis (rash around collar bone, Casal’s necklace and sun exposed areas)
How can malignant carcinoid syndrome cause pellagra-like symptoms?
Increased metabolism of tryptophan so less B3 synthesis
What is Hartnup disease?
AR loss of neutral amino acid (tryptophan) transporters on enterocytes and rental tubule cells. Leads to amino aciduria, low tryptophan and thus B3 deficiency.
Treatment for Hartnup disease?
High protein diet and nicotinic acid supplement
How does isoniazid lead to B3 deficiency?
Decreases B6, which is needed to synthesize B3
What is the name for Vitamin B5?
Pantothenic acid
What is the function of B5
essential component for coenzyme A (Acyl CoA) and fatty acid synthase?
Symptoms of Vitamin B5 deficiency
enteritis, alopecia, dermatitis, adrenal insufficiency
Which vitamin is pyridoxine?
B6
For which enzymes and reactions is B6 (PLP) a cofactor?
transaminations, carboxylations, and glycogen phosphorylase
Which neurotransmitters is B6 needed to synthesize?
Serotonin, epinephrine, norepinephrine, dopamine, GABA
What are the symptoms of B6 deficiency?
Convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemia
Why does B6 deficiency lead to sideroblastic anemia?
Impaired heme synthesis and iron excess
Which drugs can induce B6 deficiency?
Isoniazid (suspect in TB patients) and oral contraceptives
Which vitamin is biotin?
B7
Which enzymes is biotin a cofactor for?
Carboxylation enzymes (add 1C)
Pyruvate carboxylase (3–>4)
Acetyl-coA carboxylase
Propionyl coA carboxylase
What can cause B7 deficiency?
Rare but either antibiotic use or excessive ingestion of raw egg whites (body builders)
Which vitamin is B9
Folate
What is the function of folate
THF–> 1c methylation in synthesis of DNA/RNA bases
What are the symptoms of folate deficiency
Macrocytic, megaloblastic anemia with hypersegmented polymorphonuclear cells; glossitis, no neuro symptoms
How do you distinguish between a folate deficiency vs B12 deficiency?
Folate deficiency has increased serum homocysteine and normal methylmalonic acid levels. B12 deficiency has elevated homocysteine and methylmalonic acid levels
Which two conditions commonly present with folate deficiency
alchoholism and pregnancy
Where is folate absorbed in GI tract
jejunum
Which drugs can cause folate deficiency
PMS: phenytoin, methotrexate, sulfonamides
Neural tube defects are often due to deficiency in which vitamin/
Folate
What is the major source of folate
leafy green vegetables
Which vitamin is Cobalamin
B12
How long does it take for body to deplete B12
Years
What is the major source of B12
animal products
What is the function of cobalamin (B12)
Cofactor for methionine synthase and methylmalonyl-coA mutase
Which antibodies are diagnostic of pernicious anemia?
anti-intrinsic factor (low B12)
What are the symptoms of folate deficiency?
Megaloblastic, macrocytic anemia; hypersegmented PMNs, parasthesias, subacute combined degeneration of dorsal columns and lateral corticospinal tracts and spinocerebellar tracts
What is the consequence of prolonged B12 deficiency?
Irreversible nerve damage
Which vitamin is ascorbic acid
Vitamin C
What are the 3 major functions of Vitamin C?
- Facilitate iron absorption by reducing it to Fe2+
- Hydroxylation of proline and lysine in collagen synthesis (RER)
- Dopamine beta-hydroxylase (DA –> NE)
What does vitamin C deficiency cause?
Scurvy: swollen, bleeding gums; bruising, petechiae, anemia, poor wound healing, corswcrew hair, weak immune system
What does Vitamin C excess cause?
N/V/D, fatigue, calcium oxalate nephrolithiasis; increased risk of iron toxicity in people with transfusions or hemochromatosis
What is a major manifestation of zinc deficiency?
acrodermatitis enteropathica (scaling, scathing rash around buttocks and genitalia)
What are symptoms of zinc deficiency
delayed wound healing, hypogonadism, decreased axillary, facial, pubic hair, anosmia
Which condition does protein malnutrition cause?
Kwarshiorkor
Clinical manifestation of Kwarshiorkor
Edema, anemia, fatty liver (small child with swollen abdomen)
What condition does total calorie malnutrition cause?
Marasmus– muscle wasting, loss of subcutaneous fat.. emaciation
What are the three ways that alcohol is metabolized in liver?
1) Cytosol with Alcohol dehydrogenase (most common and robust)
2) Smooth ER with CYP2E1
3) Peroxisome with Catalase
What is alcohol converted to in the cytosol of hepatocytes by alcohol dehydrogenase?
Acetaldehyde
What do you gives someone with antifreeze (ethylene glycol) or methanol poisoning?
Fomepizole
How does fomepizole function?
Inhibits alcohol dehydrogenase
Which substances causes hangover symptoms?
Acetaldehyde accumulation
What is the limiting reagent in ethanol metabolism?
NAD+
How does Disulfiram interact with alcohol?
Inhibits acetaldehyde dehydrogenase, leads to hangover symptoms (nausea, vomiting, GI upset)
How does ethanol metabolism affect NADH/NAD ratio?
Increases it
What are the consequences in elevated NADH/NAD+
Lactic acidosis, fasting hypoglycemia, hepatosteatosis
How does ethanol lead to fasting hypoglycemia
elevated NADH/NAD+ favors OAA–> malate (prevents gluconeogenesis)
How does ethanol lead to hepatosteatosis (fatty liver)?
elevated NADH/NAD favors DHAP–>G3P
Which 5 metabolic reactions take place in the mitochondria
beta-oxidation (fatty acid oxidation), acetyl-coA production, TCA cycle, oxidative phosphorylation, ketogenesis
Which 6 metabolic processes take place in the cytoplasm?
Glycolysis, HMP shunt, synthesis of steroids (SER), proteins, fatty acids, cholesterol and nucleotides
Which metabolic processes take place in both cytosol and mitochondria?
Heme synthesis, urea cycle, gluconeogenesis
What is the end product of galactose metabolism?
Glucose-1-phosphate
Elevated prolactin and hyperphenylalanemia suggest PKU due to which cofactor deficiency?
tetrahydrobiopterin (BH4)
Why does decreased BH4 lead to increased prolactin?
You have less dopamine being produced to inhibit prolactin
Which enzyme deficiency leads to porphyria cutanea tarda?
uroporhyrinogen decarboxylase (UROD)
What are the sympotoms of porphyria cutanea tarda?
recurrent blistering on back of hands and forearms, small itchy spots, hyperpigmentation after rupturing
Acute intermittent porphyria occurs with defect in which enzyme?
PBG deaminase
What is the typical presentation of acute intermittent porphyria?
woman with neuropsychiatric issues and abdominal pain
Which vitamin is required for activity of ALA synthase? (Heme synthesis)
B6
Wild mushrooms contain a toxin that inhibits synthesis of which molecule?
messenger RNA (inhibit DNA Pol II)
Deficiencies of which vitamins is associated with hyperhomocysteinemia?
B6, B12, B9 (folate)
What is hyperhomocysteinemia associated with?
atherosclerosis and thrombotic events
Which urea cycle disorders are accompanied by hyperammonemia and excessive amounts of orotic acid?
Citrullinemia and ornithine transcarbamylase deficiency
Which vitamin deficiency can cause infertility and decrease serum phospholipids?
Vitamin E
