Biochem: Vitamins Flashcards
Enzymes that have biotin as a co-factor
- pyruvate carboxylase (gluconeogenesis)
- acetyl CoA carboxylase (FA synthesis)
- propionyl CoA carboxylase (odd-carbon FA, val, Met, Ile, Thr)??
Biotin Deficiency:
- MCC
- symptoms
- MCC (rare): excessive consumption of raw eggs (contain avidin, a biotin-binding protein and prevents its absorption)
- Symptoms: alopecia (hair loss), bowel inflammation, muscle pain
Thiamine (vitamin B1) deficiency
- MCC
- symptoms
- In thiamine pyrophosphate (TPP) = a cofactor for several dehydrogenase enzyme rxns.*
- MCC: alcoholism (alcohol interferes with absorption)
- Wernicke (ataxia, nystagmus, ophthalmoplegia (wide-eyed, can’t follow light)
- korsakoff (confabulation, psychosis)
- wet beri beri (high output cardiac failure)
- dry (early) beri beri (cardiac failure without fluid retention)
*beri beri = heart failure due to Vit B1 deficiency
What enzymes require Vitamin B1 (Thiamine) as a cofactor?
- In thiamine pyrophosphate (TPP) = a cofactor for several dehydrogenase enzyme rxns.*
- pyruvate dehydrogenase (PDH?)
- alpha-ketoglutarate dehydrogenase (TCA cycle)
- transketolase (HMP shunt)
- branched chain ketoacid dehydrogenase (metabolism of valine, isoleucine and leucine)
Vitamin D Toxicity
- excess Vit D can be stored in liver as 25-hydroxycholecalciferol
- excess Vit D can promote intestinal absorption of calcium and phosphate
- results in hypercalcemia
- direct result of excess Vit D = same as Vit D deficiency
- Hypercalcemia can impair renal function, and early signs include polyuria, polydipsia, and nocturne
- prolonged hypercalcemia can result in calcium deposition in soft tissues (esp kidney), causing irreversible kidney damage
Vitamin A (carotene)
- Vit A is converted to several active forms in the body associated with 2 important functions:
1. maintenance of healthy epithelium and 2. vision (retinal) - important function: retinoid acid and retinol act as growth regulators (bind intracellular receptors (zinc-finger proteins) to regulate transcription), especially in epithelium.
- retinal is important in rod and cone cells for vision
- 3 Vit A structures w different functional groups at C1:
- Retinol: hydroxyl
- retinoid acid: carboxyl
- retinal: aldehyde
Vitamin D (cholecalciferol)
important function: in response to hypocalcemia, helps normalize serum calcium levels
Vitamin B3
Niacin
- remember, Niacin = NAD(H), NADP(H)
- involved in many pathways, because cofactor for all dehydrogenase (bc NAD)
Vitamin K (menaquinone, bacteria; phytoquinone, plants)
Important functions: carboxylation of glutamic acid residues in many Ca2+ binding proteins
- importantly coagulation factors 2, 7, 9 and 10 as well as protein C and protein S
Vitamin E (alpha-tocopherol)
antioxidant in the lipid phase. protects membrane lipids from preoccupation
What is the cofactor for branched chain ketoacid dehydrogenase?
Thiamine B1
Symptoms of Vitamin D deficiency
- bone demineralization
- rickets (children): deformities of legs and other developing bones. muscle weakness common
- osteomalacia (adults, after epiphyseal fusion): less deformity than rickets. may present as bone pain and muscle weakness
Causes of Vitamin D Deficiency
- insufficient sunlight
- inadequate fortified foods (milk)
- end-stage renal disease (renal osteodystrophy)
What is the cofactor for alpha-ketoglutarate dehydrogenase?
Thiamine (B1)
Symptoms of Vitamin A deficiency
- night blindness
- keratinized squamous epithelium
- xerophthalmia, bitot spots
- keratomalacia, blindless
- follicular hyperkeratosis
- alopecia
Causes of Vitamin A deficiency
- fat malabsorption
- fat-free diets
Vitamin B2
Riboflavin (FAD, FMN)
Symptoms of Vitamin E deficiency
- hemolytic anemia
- acanthocytosis
- peripheral neuropathy
- ataxia
- retinitis pigmentosum
Causes of Vitamin E deficiency
- fat malabsorption
- premature infants
What is the cofactor for propionyl CoA carboxylase
biotin
pyruvate carboxylase is involved in what pathway?
gluconeogenesis
acetyl CoA carboxylase is involved in what pathway?
Fatty acid synthesis (carboxylation)
propionyl CoA carboxylase is involved in what pathway?
(odd-carbon FA, val, Met, Ile, Thr)??
What is the cofactor for acetyl CoA carboxylase
biotin
transketolase is involved in what pathway?
- HMP shunt
- this is the key enzyme involved in Wernicke Korsakoff syndrome
branched chain ketoacid dehydrogenase is involved in what pathway?
metabolism of valine isoleucine and leucine
A/e of isotretinoin
Teratogenic (malformation of the craniofacial, cardiac, thymic and CNS structures)
What is the cofactor for pyruvate carboxylase?
biotin
alpha-ketoglutarate dehydrogenase is involved in what pathway?
TCA cycle, carrier of FA
What is the cofactor for pyruvate dehydrogenase?
Thiamine (B1)
Vitamin B6
Pyridoxine (has an aldehyde!)
What is Pellagra?
- Vitamin B3 (niacin) deficiency
- Sx: Diarrhea, Dementia, Dermatitis, Death (if not treated)
- may also be related to deficiency of tryptophan (corn major dietary stable) which supplies a portion of the niacin requirement
Vitamin B12
Cyanocobalamin
What is the cofactor for transketolase?
Thiamine (B1)
Folic Acid deficiency
- MCC
- symptoms
- MCC: alcoholics and pregnancy (body stores depleted in 3 months)
- homocystinemia with risk of DVT and atherosclerosis
- megaloblastic (macrocytic) anemia
- deficiency in early pregnancy causes neural tube defects
lipid-soluble vitamins
- A (carotene)
- D (cholecalciferol)
- E (alpha-tocopherol)
- K (menaquinone, bacteria; phytoquinone, plants)
what enzymes require folic acid as a cofactor?
- thymidylate synthase (thymidine (pyrimidine) synthesis)
- enzymes in purine synthesis (don’t need to know specifics)
- Remember, Folic acid = THF
How does folic acid deficiency differ from Vitamin B12 deficiency?
Vit B12 deficiency has peripheral neuropathy
What condition has pellagra-like symptoms because of decreased tryptophan?
Hartnup
What enzymes have Vit B12 (cyanocobalamin) as a cofactor?
- homocysteine methyltransferase (methionine, SAM)
- methylmanoyl CoA mutase (VOMIT pathway: val, Met, Ile, Thr, Odd-carbon FA)
Ascorbate (C) deficiency:
- MCC
- symptoms
- MCC: diet deficient in citrus fruits and green veggies
- Scurvy: microcytic, hypochromic, Fe deficiency anemia
- Scurvy Sx: poor wound healing, easy bruising (perifollicular hemorrhage), bleeding gums, increased bleeding time, painful glossitis, anemia
Which pathway is thymidylate synthesis in?
thymidine (pyrimidine) synthesis
Vit B12 (Cyanocobalamin) deficiency:
- MCC
- symptoms
- MCC: Pernicious anemia
- also in aging, especially with poor nutrition
- bacterial overgrowth of terminal ileum, resection of terminal ileum secondary to Crohn disease, chronic pancreatitis
- (rarely) vegans
- infection with D. Latum
- Megaloblastic (macrocytic) anemia
- Sx: progressive, irreversible peripheral neuropathy: lose vibratory sense and proprioception. stumbling and falling/tripping
prolyl and lysyl hydrolyzes are involved in
collagen synthesis
dopamine hydroxylase is involved in
catecholamine synthesis
Ascorbate
Vitamin C
- involved in absorption of iron in the GI tract
- antioxidant
Pyridoxine (B6) is associated with which enzymes?
-pyridoxine B6, pyridoxal-P (PLP)
- aminotransferases (transaminase): AST (GOT), ALT (GPT)
- delta-aminolevulinate synthase (heme synthesis, transamination)
prolyl and lysyl hydrolyzes are associated with which vitamin?
Vitamin C
Pantothenic acid CoA
- found in all we eat, therefore seen in anorexics
- involved in fatty acid metabolism, pyruvate dehydrogenase and the TCA cycle
Riboflavin (B2) deficiency:
- symptoms
- corneal neovascularization
- cheilosis or stomatitis (cracking or scaling of lip borders and corners of the mouth)
- magenta colored-tongue
Pyridoxine (B6) deficiency:
- MCC
- symptoms
- MCC: isoniazid therapy
- sideroblastic anemia*: microcytic hypochromic anemia
- cheilosis or stomatitis (cracking or scaling of lip borders and corners of the mouth)
- convulsions
- heme not made, Fe goes into mitochondria
dopamine hydroxylase is associated with which vitamin?
Vitamin C
Pantothenic acid CoA is associated with which enzymes
- Fatty acid synthase
- fatty acyl CoA synthetase
- pyruvate dehydrogenase
- alpha-ketoglutarate dehydrogenase
What vitamin is associated with FAD(H2)?
Riboflavin (B2)
delta-aminolevulinate synthase is involved in what?
heme synthesis (transamination)
bisphosphonates
- drugs used to treat osteoporosis
- function by inhibiting osteoclast action and resorption of bone
- results in a modest increase in bone mineral density (BMD), which strengthens bone and decreases fractures
- commonly used bisphosphates: ibandronate, risedronate, alendronate. (end in -dronate)
- All water-soluble vitamins easily wash out of the body except?
- where are these stored? and for how long?
- B12 (cobalamin) and B9 (folate)
- B12 stored in liver for 3–4 years.
- B9 stored in liver for 3–4 months.
B-complex deficiencies often result in ___
B-complex deficiencies often result in dermatitis, glossitis, and diarrhea.
Vitamin B1, aka
thiamine: TPP
Vitamin B5, aka
pantothenic acid: CoA
mineral oil intake can cause ____ vitamin deficiencies.
mineral oil intake can cause fat-soluble vitamin deficiencies
Retinol (Vitamin A)
- Function
- where do you get it?
- Antioxidant
- Found in liver and leafy vegetables.
- 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).
- oral isotretinoin used to treat severe cystic acne (teratogenic)
- Use all-trans retinoic acid to treat acute promyelocytic leukemia
Deficiency of Vitamin A (retinol) symptoms
- Night blindness (nyctalopia)
- dry, scaly skin (xerosis cutis)
- corneal degeneration (keratomalacia)
- Bitot spots on conjunctiva
- immunosuppression
Acute Vitamin A Toxicity
- Acute toxicity: nausea, vomiting, vertigo, and blurred vision
Chronic Vitamin A Toxicity
- Chronic toxicity: alopecia, dry skin (eg, scaliness), hepatic toxicity and enlargement, arthralgias, and pseudotumor cerebri.
- Teratogenic (cleft palate, cardiac abnormalities), therefore a negative pregnancy test and 2 forms of contraception are required before isotretinoin (vitamin A derivative) is prescribed
Vitamin B1 (thiamine) - function
- In thiamine pyrophosphate (TPP), a cofactor for several dehydrogenase enzyme reactions:
1. Pyruvate dehydrogenase (links glycolysis to
TCA cycle)
2. α-ketoglutarate dehydrogenase (TCA cycle)
3. Transketolase (HMP shunt)
4. Branched-chain ketoacid dehydrogenase - Think (ATP):
A: α-ketoglutarate dehydrogenase
T: Transketolase
P: Pyruvate dehydrogenase.
Wernicke-Korsakoff syndrome
- what’s damaged
- symptoms
- confusion, ophthalmoplegia, ataxia (classic triad) +
- confabulation
- personality change
- memory loss (permanent).
- Damage to medial dorsal nucleus of thalamus, mammillary bodies.
beri beri Symptoms
- Dry Beri Beri:
- polyneuritis
- symmetrical muscle wasting. - Wet beriberi:
- high-output cardiac failure (dilated cardiomyopathy), edema.
* Spell beri beri as Ber1Ber1 to remember vitamin B1
Vitamin B2 (riboflavin) function
- Component of flavins FAD and FMN
- used as cofactors in redox reactions
- ex) the succinate dehydrogenase reaction in the TCA cycle.
- “(F)AD and (F)MN are derived from ribo(F)lavin
- (B2 ≈ 2 ATP)
Vitamin B2 (riboflavin) deficiency
- The 2 C’s of B2:
- Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth)
- Corneal vascularization
Deficiency of Vitamin B1 (Thiamine)
- Impaired glucose breakdown leads to
- ATP depletion worsened by glucose infusion
- highly aerobic tissues (eg, brain, heart) are affected first.
- Wernicke-Korsakoff syndrome and beriberi.
- Seen in malnutrition and alcoholism (2° to malnutrition and malabsorption).
- Diagnosis made by increase in RBC transketolase activity following vitamin B1 administration
Vitamin B3 (niacin) Function
- Constituent of NAD+, NADP+ (used in redox reactions).
- Derived from tryptophan
- Synthesis requires vitamins B2 and B6
- Used to treat dyslipidemia
- lowers levels of VLDL and raises levels of HDL.
- NAD derived from Niacin
- (B3 ≈ 3 ATP)
Vitamin B3 (niacin) Deficiency
- Glossitis.
- Severe deficiency leads to pellagra, which can be caused by Hartnup disease, malignant carcinoid syndrome (increased tryptophan metabolism), and isoniazid (decreased vitamin B6)
- Symptoms of pellagra (“The 3 D’s of B3”):
1. Diarrhea
2. Dementia (also hallucinations)
3. Dermatitis: - C3/C4 dermatome circumferential “broad collar” rash [Casal necklace]
- hyperpigmentation of sun-exposed limbs
Vitamin B3 (niacin) Excess
- Facial flushing (induced by prostaglandin, not histamine; can avoid by taking aspirin with niacin)
- hyperglycemia
- hyperuricemia
Hartnup Disease
- autosomal recessive
- Deficiency of neutral amino acid (ex tryptophan) transporters in proximal renal tubular cells and on enterocytes
- causes neutral aminoaciduria
- and decreased absorption from the gut
- decreased tryptophan for conversion to niacin
- this causes pellagra-like symptoms.
- Treat with high- protein diet and nicotinic acid
Vitamin B5 (pantothenic acid) Function
- Essential component of coenzyme A (CoA, a cofactor for acyl transfers)
- and fatty acid synthase
- B5 is “pento”thenic acid
Vitamin B5 (pantothenic acid) Deficiency
- Dermatitis
- enteritis
- alopecia
- adrenal insufficiency
Vitamin B6 (pyridoxine) Function
- Converted to pyridoxal phosphate (PLP), a cofactor used in
1. transamination (eg, ALT and AST)
2. decarboxylation reactions
3. glycogen phosphorylase. - Synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters including serotonin, epinephrine, norepinephrine (NE), dopamine, and GABA
Vitamin B6 (pyridoxine) Deficiency
- Convulsions
- hyperirritability
- peripheral neuropathy (deficiency inducible by isoniazid and oral contraceptives)
- sideroblastic anemias due to impai`red hemoglobin synthesis and iron excess
Vitamin B7 (biotin) function
- “Avidin in egg whites avidly binds biotin”
- Cofactor for carboxylation enzymes (which add a 1-carbon group):
1. Pyruvate carboxylase: converts pyruvate (3C) to oxaloacetate (4C)
2. Acetyl-CoA carboxylase: converts acetyl-CoA (2C) to malonyl-CoA (3C)
3. Propionyl-CoA carboxylase: converts propionyl-CoA
(3C) to methylmalonyl-CoA (4C)
Vitamin B7 (biotin) deficiency
- Relatively rare
- Dermatitis
- alopecia
- enteritis.
- Caused by antibiotic use or excessive ingestion of raw egg whites
Vitamin B9 (folate) function
- Converted to tetrahydrofolic acid (THF)
- a coenzyme for 1-carbon transfer/methylation reactions
- Important for the synthesis of nitrogenous bases in DNA and RNA.
- Supplemental maternal folic acid in early pregnancy to decrease risk of neural tube defects
Causes of Vitamin B9 (folate) deficiency and Labs
- MC vitamin deficiency in the US.
- Seen in alcoholism and pregnancy.
- Deficiency can be caused by several drugs (eg, phenytoin, sulfonamides, methotrexate)
2. Labs: - elevated homocysteine
- normal methylmalonic acid levels
Vitamin B9 (folate)
- found where?
- absorbed where?
- stored where?
- Found in leafy green vegetables.
- (FOLate from FOLiage)
- Absorbed in jejunum
- Small reserve pool stored primarily in the liver
- Features of Vitamin B9 (folate) Deficiency
- Labs
- Macrocytic, megaloblastic anemia
- hypersegmented polymorphonuclear cells (PMNs)
- glossitis
- no neurologic symptoms (as opposed to vitamin B12 deficiency)
- Labs:
- elevated homocysteine
- normal methylmalonic acid levels
Zinc Function
- Mineral essential for the activity of 100+ enzymes.
- Important in the formation of zinc fingers (transcription factor motif)
Zinc Deficiency
- Delayed wound healing
- hypogonadism
- decreased adult hair (axillary, facial, pubic)
- dysgeusia (distortion of the sense of taste)
- anosmia
- acrodermatitis enteropathica
- May predispose to alcoholic cirrhosis
Kwashiorkor Malnutrition
- Protein malnutrition resulting in:
- skin lesions
- edema due to decreased plasma oncotic pressure
- liver malfunction (fatty change due to decreased apolipoprotein synthesis).
- Clinical picture is small child with swollen abdomen
- Kwashiorkor results from a protein-deficient MEAL:
Malnutrition
Edema
Anemia
Liver (fatty)
Marasmus Malnutrition
- “Marasmus results in Muscle wasting”
- Total calorie malnutrition resulting in emaciation (tissue and muscle wasting, loss of subcutaneous fat)
- +/– edema
Vitamin D2
- D2 = ergocalciferol
- ingested from plants
Vitamin D3
- 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 of Vitamin D
- increased intestinal absorption of calcium and phosphate
- increased bone mineralization at low levels
- increased bone resorption at higher levels
Vitamin D 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
Excess of Vitamin D
- Hypercalcemia
- hypercalciuria
- loss of appetite
- stupor.
- Seen in granulomatous disease (activation of vitamin D by epithelioid macrophages)
Vitamin E (tocopherol/tocotrienol) Function
- Antioxidant (protects RBCs and membranes from free radical damage)
- Can enhance anticoagulant effects of warfarin
Vitamin E (tocopherol/tocotrienol) Deficiency
- Hemolytic anemia
- acanthocytosis
- muscle weakness
- posterior column and spinocerebellar tract demyelination.
- Neurologic presentation may appear similar to vitamin B12 deficiency, but WITHOUT
- megaloblastic anemia
- hypersegmented neutrophils, or
- increased serum methylmalonic acid levels
Vitamin K (phytomenadione, phylloquinone, phytonadione) Function
- “K is for Koagulation”
- Cofactor for the γ-carboxylation of glutamic acid residues on various proteins required for blood clotting
- Synthesized by intestinal flora
- Necessary for the maturation of clotting factors II, VII, IX, X, and proteins C and S.
- Warfarin = vitamin K antagonist
Vitamin K (phytomenadione, phylloquinone, phytonadione) Deficiency
- Neonatal hemorrhage with increased PT and increased aPTT 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 hemorrhagic disease of the newborn
Vitamin C (ascorbic acid) Function
- Found in fruits and vegetables
- Antioxidant
- facilitates iron absorption by reducing it to Fe2+ state.
- (Pronounce “ABSORBic” acid.)
- Necessary
for hydroxylation of proline and lysine in collagen synthesis. - Necessary for dopamine β-hydroxylase, which converts dopamine to NE.
- Ancillary treatment for methemoglobinemia by
reducing Fe3+ to Fe2+
Vitamin C (ascorbic acid) Deficiency
- “Vitamin C deficiency causes sCurvy due to a Collagen synthesis defect”
- Scurvy: swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, “corkscrew” hair.
- Weakened immune response
Vitamin C (ascorbic acid) Excess
- Nausea, vomiting, diarrhea, fatigue
- calcium oxalate nephrolithiasis.
- Can increase risk of
iron toxicity in predisposed individuals
(eg, those with transfusions, hereditary hemochromatosis)
Vitamin B12 (cobalamin)
- Function
- Where is it found?
- Storage?
- Cofactor for methionine synthase (transfers CH3 groups as methylcobalamin)
- and methylmalonyl-CoA mutase.
- Found in animal products
- Synthesized only by microorganisms.
- Very large
reserve pool (several years) stored primarily in the liver
- Causes of Vitamin B12 (cobalamin) Deficiency
2. Diagnosis
- Deficiency caused by: - malabsorption (eg, sprue, enteritis, Diphyllobothrium latum)
- lack of intrinsic factor (pernicious anemia, gastric bypass surgery)
- absence of terminal ileum (surgical resection, eg, for Crohn disease)
- or insufficient intake (eg, veganism). - Anti-intrinsic factor antibodies diagnostic for pernicious anemia
Scurvy Symptoms
- swollen gums
- bruising
- petechiae
- hemarthrosis
- anemia
- poor wound healing
- perifollicular and subperiosteal hemorrhages
- “corkscrew” hair
Signs/Symptoms of Vitamin B12 (cobalamin) Deficiency
- Macrocytic, megaloblastic anemia
- hypersegmented PMNs
- paresthesias
and subacute combined degeneration (degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) - due to abnormal myelin.
- Associated with increased serum homocysteine and methylmalonic acid levels.
- Prolonged deficiency can lead to irreversible nerve damage
