Biochemistry-Nutrition Flashcards
What vitamins are fat soluble?
ADEK (absorption dependent on the gut and pancreas)
Toxicity of these is more common than for water-soluble vitamines b/c fat soluble vitamins accumulate in fat
Malabsorption syndromes with steatorrhea such as cystic fibrosis and sprue or mineral oil intake can cause fat-soluble vitamin deficiencies
Notes about water soluble vitamins
all wash out easily from the body except B12 amd folate (stored in the liver)
B-complex deficiencies often result in what clinical triad:
dermatitis
glossitis
diarrhea
B1 (thiamine: TTP)
B2 (riboflavin: FAD, FMN)
B3 (niacin: NAD+)
B5 (pantothenic acid: CoA)
B6 (pyridoxine: PLP)
B7 (biotin)
B9 (folate)
B12 (cobalamin)
C (ascorbic acid)
What is the function of vitamin A?
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 tx measles and AML subtype M3 (retinol)
What foods contain a lot of vitamin A?
liver and leafy veggies
What does deficiency in vitA cause?
night blindness (nyctalopia)
scaly skin (xerosis cutis)
corneal degeneration (keratomalacia)
bitot spots on conjnctiva (below)
immunosuppression
How would a vitA OD present?
acute toxicity: N/V, vertigo, and blurred vision
chronic toxicity: alopecia, dry skin, hepatic toxicity and enlargment, arthralgias, and pseudotumor cerebri
vitA OD is teratogenic. How?
causes cleft palate, cardiac abnormalities (thus a neg pregnancy test is required before isotreinoin is prescribed for severe acne)
What is the function of vitB1 (thiamine)?
In thiamine pyrophosphate (TPP), a cofactor for several dehydrogenase rxns including:
pyruvate dehydrogenase (links glycolysis to TCA cycle)
a-ketoglutarate dehydrogenase (TCA cycle)
Branched-chain ketoacid dehydrogenase
transketolase (HMP shunt)
What does deficiency of thiamine cause?
impaired glucose breakdown leading to ATP depletion worsened by glucose infusion (highly aerobic tissues such as the brain and heart are affected first)
can cause Wernicke-Krsakff syndrome and beriberi
seen in alcoholism and malnutrition
How is the diagnosis of thiamine deficiency made?
increased in RBC transketolase activity following vitB1 administration
What is Wernicke-Korsakoff syndrome?
confusion, ophthalmoplegia, ataxia (classic triad)
+ confabultation, personality change, memory loss (permanent)
Wernicke-Korsakoff syndrome is marked by damage to what brain structures?
medial dorsal nucleus of the thalamus, and mamillary bodies
What is the difference between wet and dry beriberi?
Wet: high-ouput cardiac failure (dilated cardiomyopathy), edema
Dry: polyneuritis, symmetrical muscle wasting
What is the function of vitB2 (riboflavin)?
component of flavins FAD and FMN, used as cofactor in redox rxns (e.g. the succinate dehydrogenase rxn in the TCA cycle)
What does a deficiency of riboflavin cause?
cheliosis (inflammation of lipds, scaling, and corner fissues)
corneal vascularization
What is the function of vitB3 (niacin)?
constituent of NAD+, NADP+ (used in redox rxns)
derived from tryptophan (synthesis requires vitB2 and vitB6)
used to tx dyslipidemia (lowers levels of VLDL and raised levels of HDL)
What does deficiency of vitB3 (niacin) cause?
glossitis
severe deficiency leads to pellagra, which can be casued y Hartnup disease (decreased tryptophan absorption), malignant carcinoid syndrome (increased tryptophan metabolism) and isoniazid (decreased vitB6)
What are the symptoms of pellagra?
diarrhea, dementia (also hallucinations), and dermatitis (C3/C4 dermatome ‘broad collar’ rash, aka casal necklace), and hyperpigmentation of sun-exposed limbs
What does OD of niacin cause?
facial flushing (induced by prostaglandins, not histamine; can avoid by taking aspirin with niacin)
hyperglycemia, hyperuricemia
What is the function of vitB5 (pantothenic acid)?
essential component of CoA and fatty acid synthase
What would a vitB5 (pantothenic acid) deficiency cause?
dermatitis, enteritis, alopecia, and adrenal insufficiency
What is the function of vitB6 (pyridoxine)?
converted to pyridoxal phospahte (PLP), a cofactor used in transamination (e.g. ALT and AST) decarboxylation rxns, glycogen phosphorylase
synthesis of cystathionine, heme, niacin, histamine, and NTMs including serotonin, epi, nor, dopamine, and GABA
What does deficiency of vitB6 (pyridoxine) cause?
convulsions, hyperirritability,
peripheral neuropathy (deficiency inducible by isoniazid and oral contraceptives)
sideroblastic anemia due to impared hemoglobin synthesis and iron excess
What is the function of vitB7 (biotin)?
cofactor for carboxylation enzymes (which add 1C):
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)
How does deficiency of vitB7 (biotin) present?
relatively rare
dermatitis, alopecia, enteritis (caused by ABX use of excessive ingestion of raw egg whites)
What is the function of vitB9 (folate)?
converted to tetrahydrofolic acid (THF), a coenzyme for 1C-transfer/methylayion rxns
important for the synthesis of nitrogenous bases in DNA/RNA
What foods contain lots of vitB9 (folate)?
leafy green veggies (absorbed in the jejunum and a small reserve pool is stored in the liver)
What does deficiency of vitB9 (folate) cause?
macocytic, megaloblastic anemia
hypersegmented PMNs
glossitis
NO neurological symptoms (unlike B12 deficiency)
What labs confirm deficiency of vitB9 (folate)?
elevated homocysteine, normal methylmalonic acid levels
seen in alcoholism and pregnancy
What drugs can cause deficiency of vitB9 (folate)?
phenytoin
sulfonamides
methotrexate
What is the function of vitB12 (cobalamin)?
cofactor for homocyteine methyltransferase (transfers CH3 groups) and methylmalonyl-CoA mutase (converts methylmalonyl COA to succinyl CoA during heme production)
Describe the methionine production pathway
homocysteine is converted to methionine by addition of a CH3 group from THF-CH3 using homocysteine methyltransferase and B12 as a cofactor
Methionine can then converted to SAM using ATP, which can then be reconverted to homocyteine via loss of a CH3 group
What foods is vitB12 found in?
animal products
synthesized only by microorganisms and humans generally have very large pools that can last for months in the liver
What usually causes vitB12 deficiency?
insufficient intake (e.g. veganism), malabsorption (e.g. sprue, enterits, Diphellobothrium latum infection), lack of intrinsic factor, or lack of terminal ileum
How does vitB12 deficiency present?
macrocytic, megaloblastic anemia
hypersegmented PMNs
paresthesias and subacite combined degeneration (degen of the dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) due to abnormal myelin
How is vitB12 deficiency diagnosed?
elevated serum homocysteine and methylmalonic acid levels
What is the function of vitC (ascorbic acid)?
antioxidant
facilitates iron absorption from the duodenum by reducing it to Fe2+ (ancillary tx for methemoglobinemia)
necessayr for hydroxylation of proline and lysine in collagen synthesis
needed for dopamine-B-hydroxylase, which converts dopamine to NE
Where is vitC found?
fruits and veggies
What vitC deficiency cause?
Scurvy- swollen gums, brusing, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, “corkscrew” hair
results from collagen defects
What does vitC OD cause?
N/V, fatigue
diarrhea
calcium oxalaye nephrolithiasis
increased risk of iron toxicity in those with transfusions, hereditary hemochromatosis
What are the forms of vitD?
D2= erocalciferol- 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 (calcitrol)= active form
What are the functions of vitD?
increased intestional absorption of calcium and phosphate and increase bone mineralization
What does deficiency of vitD cause?
rickets in children (bone pain and deformity)
osteomalacia in adults
What is the function of vitE (tocopherol)?
antioxidants (protects RBCS and membranes from free radical damage)
can enhance the anticoagulant effects of warfarin
What does deficiency of vitE (tocopherol) cause?
hemolytic anemia
acenthocytosis
muscle weakness
posterior columna and spinocerebellar tract demyelination
Note that the neurological presentation is similar to vitB12 deficiency, but without megaloblastic anemia, hypersegmented PMNs, or elevated serum methylmalonic acid levels
What are the functions of vitK (phytomenadione, phylloquinone, phytonadione)?
cofactor for the y-carboxylation of glutamic acid residues on various proteins required for blood clotting (synthesized by intestinal flora)
needed for the maturation of clotting factors II, VII, IX, and X and proteins C/S
What does deficiency of vitK cause (via ABX or warfarin, etc.)?
neonatal hemorrhage with elevated PT an aPTT but normal bleeding time (neonates have sterile intestines and are unable to synthesize vitK)
can also occur after ABX use
Note that vitK is NOT in breast milk and neonates need supplements
What is the function of zinc?
mineral essential for the activity of 100+ enzymes and zinc fingers
How might zinc deficiency present?
delayed wound healing, hypogonadism
decreased adult hair (axillary, facial, pubic)
dyseusia (a condition in which a foul, salty, rancid, or metallic taste sensation will persist in the mouth.)
anosmia
acrodermatitis enteropathica
may predispose to alcoholic cirrhosis
What is Kwashiorkor?
protein malabsoprtion resulting in skin lesions, edema due to decreased plasma oncotic pressure, liver malfunction (fatty change due to decreased apolipoprotein synthesis)
What is Marasmus?
total calorie malnutrition resulting in tissue and msucle wasting, loss of subQ fat, and variable edema
How is ethanol metabolized?
ethanol is converted to acetaldehyde via alcohol dehydrogenase (using NAD+; zero-order kinetics) in the cytosol (or via catalse in the peroxisome or CYP2E1 in the microsome)
and then to acetate via acetaldehyde dehdyrogenase (using NAD+)
What drugs blocks the action of alcohol dehdyrogenase?
fomeprizole (an antidote for emthanol or ethylene glycol poisoning)
What drugs blocks the action of acetaldyhde dehdyrogenase?
disulfram (acetaldehyde accumulates, leading to hangover symptoms)
Ethanol metabolism increased the NADH/NAD+ ratio in the liver leading to:
pyruvate conversion to lactate (lactic acidosis)
oxaloacetate conversion to malate (prevents gluconeogenesis causing a fasting hypoglycemia)
dihydroxyacetone phosphate conversion to glycerol-3-phosphate (combined with fatty acids to make TAGs leading to heptatosteatosis)
Note also the an icnreased NADH/NAD+ ratio disfavors TCA production of NADH, resulting in increased utilization of acetyl-CoA for ketogenesis (leading to ketoacidosis) and lipogenesis (hepatosteatosis)
