Flashcards in Nutrition 2 Deck (55):
Describe the following vitamins as fat-soluble or water-soluble. Describe the difference between fat-soluble and water-soluble.
Vitamin A (retinol)
Vitamin B 12
Vitamin D (cholecalciferol)
Vitamin E (tocopherols)
Vitamin K (phylloquinone)
Fat-soluble include A (retinol), D (cholecalciferol), E (tocopherols) & K (phylloquinone) Functions vary
Tend to be stored in the body: adipose tissue or liver, precursor of D found in dermis & epidermis
Water-soluble include thiamin, riboflavin, niacin, B6, B12, pantothenic acid, biotin, folic acid, vitamin C
Primarily function as coenzymes
Excess tends to be excreted
A 26-year-old pregnant woman complains of persistent, dry, ulcerated skin over her knees and elbows. Examination of her eyes reveals small, gray plaques on the conjunctiva. Which of the following is the most likely diagnosis?
a. Ascorbic acid deficiency
b. Excessive α-tocopherol intake
c. Excessive cholecalciferol intake
d. Retinol deficiency
e. Thiamine deficiency
Describe the two forms of Vitamin A -Retinoids.
comes in 2 forms from vegetable foods, typically water soluble and can pass into basolateral cells in gut..
animal foods- fat soluble, digested into retinyl esters, absorbed across membrane. bound internally goes into chylomicrons along w rest of fat, taken to liver and broken down again to retinal esters, stored in liver in conjunction w fatty acids or secreted and used for its functions
- Preformed retinol found in animal foods
- Carotenoids from vegetables (yellow/orange/red pigments) – see figure 2 below
- Digestion & absorption: along with fats in foods, retinoids packaged in chylomicrons for transport through lymph and plasma to liver
- Retinol transported in plasma by retinol binding protein (RBP) bound to transthyretin; within cells by cytosolic retinol binding protein (CRBP)
- 50-85% retinoid storage in liver as retinyl esters
- In absence of inflammation, low plasma retinol indicates depleted hepatic stores (deficiency)
- Retinol and retinoic acid excreted primarily via bile
Describe the primary functions of Vitamin A.
Prosthetic group of visual pigments?
Nuclear modulator of gene expression?
What are the primary active forms of Vitamin A?
Prosthetic group of visual pigments - Retinal
Nuclear modulator of gene expression - Retinoic Acid
Primary active forms of Vitamin A: retinaldehyde and retinoic acid
Describe the formation of retinaldeyhyde and retinol and retinoic acid.
Oxidative cleavage of beta-carotene yields all-trans-retinaldehyde (retinal), further metabolized to retinol & retinoic acid
Describe the functions of Vitamin A in regards to vision.
11-cis-retinal (AKA retinaldehyde) binds with opsin (transmembrane protein) in rods or related proteins in cones of the retina
Photoexcited rhodopsin activates a G-protein that leads to closing of ion channel and hyperpolarization of rod membrane to initiation of nerve impulse
Rod cells responsible for vision in dim light – very sensitive
Cone cells responsible for color differentiation
Describe cellular growth and differentiation of retinoic acid. How is it important in development?
- Retinoic acid essential for cellular proliferation and differentiation through genomic action
- Retinoic acid critical in early embryogenesis: required for normal limb development and formation of the heart, eyes and ears
- Excess retinoic acid can be teratogenic
- Epithelial cell differentiation significantly inhibited by vitamin A deficiency
In absence of retinoic acid, repressor inhibits transcription. Transcription activated by retinoic acid binding to RAR resulting in conformational change in RAR that recruits activators.
Important during development
Describe the immune function of Vitamin A.
- Cell-mediated and antibody-mediated immune responses diminished in deficiency
- Immune responses restored quickly after supplementation suggesting structure for adequate immune response stays intact but signaling pathways impaired in deficiency.
What are the precursors to retinoids? Describe them.
- Class of greater than 600 lipid soluble compounds; precursors to retinoids
- Carotenoids are pigmented – yellow to red ... think carrots
- Common carotenoids: beta-carotene, alpha-carotene, lycopene, and lutein.
How might you clinically assess for Vitamin A status?
Decreased plasma retinol indicates deficiency
Clinical assessment: examination of conjunctiva for changes in epidermis
Describe Vitamin A deficiency. What is an early sign?
Cardinal sign? (Describe the stages)
Night blindness early sign
Leads to dedifferentiation of epithelial cells epithelial keratinization, poor appetite, poor growth, xerophthalmia
Xerophthalmia cardinal sign of clinical deficiency
1. Early conjunctival xerosis – dryness of the conjunctival surface
2. Bitot’s spots –single or multiple areas of desquamated, keratinized conjunctival cells together with lipid accumulation; not unique to vitamin A deficiency unless accompanied by conjunctival xerosis; temporally (rather than nasally) situated
3. Keratomalacia –entire thickness of cornea becomes cloudy, gelatinous mass; in very young children, may develop very rapidly in absence of xerosis or Bitot’s spot formation. Minimal reaction in surrounding tissues & lack of discharge from eye are characteristic and assist in differentiation from other conditions. Blindness results; irreversible.
Describe Vitamin A Toxicity.
Vitamin A Toxicity
Acute toxicity includes nausea, vomiting, headache, peeling of the skin
Chronic exposure leads to weight loss, fever, bone tenderness and itchy rash
Retinoic acid can be teratogenic
really bright red gingiva right along teeth- cardinal sign of toxicity
Hypervitaminosis A from acute or chronic overconsumption of preformed vitamin A; overdosing on dietary supplements
Hypercarotenosis: orange tinge to skin; sclerae remain clear distinguishing the condition from jaundice; diets high in carotenes; no serious negative effects
Describe Vitamin D. What is it's name?
Where is it synthesized?
Vitamin D synthesized in dermis and epidermis from metabolite of cholesterol (7-dehydrocholesterol)
Principal function in all vertebrates - maintain serum calcium and phosphorus concentrations in a range that supports cellular processes, neuromuscular function and bone ossification
- Mechanisms: increase intestinal absorption, increase renal reabsorption and increase bone resorption
Primary function – maintain serum Ca (and P) concentrations
increase intestinal absorption
increase bone resorption
increase renal reabsorption
Functions through regulation of gene expression
Describe Vit. D deficiency.
Describe the physical manifestations in children and adults.
What is Harrison's sulcus?
Significant prevalence of subclinical vitamin D deficiency in US population, highest among African Americans (42%) – in whites 4.2% - controversy over significance
Rickets in children – failure of appropriate deposition of mineral in matrix of epiphyseal cartilage
Rickets relatively rare in US – almost all reported cases of primary rickets observed in breastfed infants of color
Osteomalacia in adults – stimulated mobilization of calcium and phosphorus from bone to maintain serum concentrations
physical manifestations include bowing of legs and arms to lesser extent
Skull in rickets – frontal bones prominent and bossed. Fontanelles delayed in closing.
Harrison’s sulcus – bilateral indentation of the lower ribs at site of diaphragm attachment
Uncalcified osteoid – metaphyses are concave and irregular; zone of uncalcified osteoid increased (poor ossification in junctions)
What is the most active form of Vitamin E?
What is the function of Vitamin E?
What are surgical guidelines concerning Vitamin E?
How is oxidized Vitamin E reduced?
alpha-tocopherol- most active form
Digested and absorbed along with foods, found primarily in vegetable oils containing high amounts of PUFAs
Primary function - scavenger of free radicals and peroxyl radicals
Other functions - inhibition of platelet aggregation & increased vasodilation
- Functions as antioxidant, regulated by liver α-tocopherol transfer protein (α-TTP)
- Potent peroxyl radical scavenger, especially protects PUFA in phospholipids of membranes and plasma lipoproteins
Surgery guidelines – stop vitamin E supplements 2 - 4 weeks prior to elective surgery
Oxidized vitamin E is reduced by vitamin C.
How is Vitamin E status assessed?
What are dietary sources of Vitamin E?
Assessment of Vitamin E Status
- Plasma alpha-tocopherol
Vegetable oils; only plants synthesize vitamin E
- Supplements major source of vitamin E in US
Describe Vitamin E deficiency.
What type of individuals are at risk/ What type of individuals might we be more likely to see this in?
What are the primary manifestations?
Rare in humans; almost never from dietary deficiencies
- Genetic mutation in α-TTP gene - associated with AVED syndrome (ataxia with vitamin E deficiency); neurologic abnormalities with progressive peripheral neuropathy
- Individuals with abetalipoproteinemia also experience deficiency & individuals with fat malabsorption syndromes
Primary manifestations: spinocerebellar ataxia, skeletal myopathy and pigmented retinopathy
A 23-year-old, single, unemployed woman is in her eighth month of pregnancy. Her first child, born at home and exclusively breastfed, had prolonged diarrhea and died from an intracranial hemorrhage at 1 month of age. To help prevent a similar problem in this pregnancy, the resident gives her a prescription for a vitamin and advises her to take one 20-mg tablet each day. He also informs her that the infant should receive an injection of this vitamin soon after birth. The vitamin prescribed is required as a coenzyme by which of the following enzymes?
a. delta-aminolevulinate synthase
b. gamma-glutamyl carboxylase
c. Homocysteine methyltransferase
d. Prolyl hydroxylase
Describe Vitamin K. What name?
What is its role?
What is its primary function?
Vitamin K – Phylloquinone
Primary function – regulation of blood clotting protein synthesis; 7 vitamin K-dependent proteins involved in coagulation (functions as coenzyme in carboxylation reactions - carboxylases)
also involved in carboxylation of bone development proteins: osteocalcin & matrix GLA protein
- Co-factor for membrane-bound carboxylase system involved in posttranslational carboxylation of glutamate residues in several proteins
- Co-factor for carboxylation of non-coagulation-related proteins, including bone-associated proteins: osteocalcin and matrix Gla protein
How do you assess for Vit. K status? What would suggest deficiency?
Plasma prothrombin levels; below 50% normal values suggest deficiency
Describe Vitamin K Deficiency.
What is the cardinal sign?
Cardinal sign: bleeding, poor coagulation
- Primary deficiency uncommon in healthy adults; reduced vitamin K-dependent coagulation factors in adults almost always secondary to disease or drug therapy
- Primary vitamin K deficiency rare in adults – ubiquitous in foods, salvage system that recycles K in liver & other tissues, production by intestinal bacteria
- Bleeding primary manifestation of K deficiency
- Primary deficiency in breastfed infants significant cause of morbidity & mortality in developing countries
- Newborns at high risk - hemorrhagic disease of the newborn
- Vitamin K prophylaxis given at birth in most developed countries
- Deficiency in breast-fed newborn remains significant cause of morbidity & mortality world-wide: placenta poorly transmits, liver immature regarding prothrombin synthesis, intestine sterile at birth & breast milk low in vitamin K; hemorrhagic disease of newborn; vitamin K prophylaxis given at birth in most developed countries
What are the B vitamins?
Describe the functions of Vitamin B1.
Coenzyme for what enzymes?
- Coenzyme for oxidative decarboxylation of:
-Branched-chain oxo-acid dehydrogenase
-alpha ketoglutarate dehydrogenase
Coenzyme (as thiamin pyrophosphate – TPP) of active aldehyde transfers including oxidative decarboxylation of alpha-keto acids & transketolase reaction
- Required for metabolism of carbohydrates & branched-chain amino acids
- Possible role in neurotransmission independent of coenzyme function; thiamin triphosphate (TTP) may be involved in sodium conductance at axonal membranes
Thiamine is a cofactor for several essential enzymes in the Krebs cycle and the pentose phosphate pathway, including alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and transketolase
What happens if there is not enough thiamin?
if not enough thiamin… CAC cycle stops. glucose in blood goes up…
PDH would not work without thiamin
What is thiamin deficiency caused by? What are the most vulnerable populations?
- Caused by inadequate intake, decreased absorption, defective transport, impaired synthesis of TPP or increased requirement
- Populations most vulnerable: breast-fed infants of deficient mothers, adults with high carbohydrate intake from processed non-fortified grains & chronic alcoholics
Describe the following:
Wet beriberi or cardiac beriberi
Dry beriberi – peripheral neuropathy, calf muscle tenderness, bilateral “wrist and ankle drop”, symmetric impairment of sensory, motor and reflex functions affecting limb segments, motor and reflex functions affecting distal portions of limbs; calf muscle tenderness and difficulty in rising from squatting position
Wet beriberi or cardiac beriberi– edema, tachycardia, cardiomegaly and congestive heart failure plus the neuropathy described above, high cardiac output, low peripheral and pulmonary vascular resistances
Cerebral beriberi – Wernicke’s encephalopathy or Wernicke-Korsakoff syndrome; mental confusion, progressive to bilateral 6th nerve paralysis and coma – seen in severe alcoholism in US (poor diet - also, ethanol impairs absorption of thiamin across basolateral membrane in gut )
Infantile beriberi – often seen in babies of women with asymptomatic deficiency, aphonia, polyneuropathy and cardiac failure
What are the two most common instances of thiamin deficiency in US?
alcoholics and gastric bypass
In Wernicke's encephalopathy in alcoholism, should thiamin be administered before or after glucose, why?
Wernicke’s encephalopathy in alcoholism – thiamin deficiency – must administer IV thiamin PRIOR to glucose otherwise can result in coma and possibly death due to rapid hyperglycemia
A 57-year-old alcoholic man is brought to the emergency department in a state of global confusion, psychosis and ataxia. On examination, ophthalmoplegia and polyneuropathy are also noted. Administration of which of the following would be the most appropriate treatment for this patient?
A 50-year-old chronic alcoholic presents with dementia, paralysis of lateral gaze, and difficulty walking. The vitamin deficient in this patient is required as a cofactor for which of the following enzymes?
a. Aspartate aminotransferase
b. Methylmalonyl-CoA mutase
c. Prolyl hydroxylase
d. Pyruvate carboxylase
e. Pyruvate dehydrogenase
A 34-year-old woman presents to her physician complaining of oral ulcers. A careful history reveals she is a strict vegetarian and does not eat fish, meat, poultry, eggs or dairy products. She is found to have a severe riboflavin deficiency. The function of which of the following enzymes in the citric acid cycle would be most directly affected by the riboflavin deficiency?
b. Citrate synthase
c. Isocitrate dehydrogenase
d. Malate dehydrogenase
e. Succinate dehydrogenase
What is its role?
What enzymes is it a cofactor for?
Most important role as redox coenzyme (FAD & FMN) in energy-yielding reactions in citric acid cycle and beta-oxidation – electron carriers for the enzymes
succinate dehydrogenase – TCA cycle
acyl CoA dehydrogenases – beta-oxidation
Describe riboflavin deficiency.
rarely occurs as isolated deficiency
relatively non-specific signs & symptoms
include sore throat, cheilosis, angular stomatitis, glossitis, seborrheic dermatitis
excess produces fluorescent yellow urine – can be used as marker of drug-taking compliance
An 83-year-old man is brought to the physician because of diarrhea and vomiting for the past month. He is unable to give a clear history, but his daughter reports that he has been “quite sad” lately and often seems very confused. His diet consists of dried cereal and maize (corn); he never eats milk or eggs. Physical examination shows sharply demarcated plaques on his hands, feet and around his neck. Which of the following amino acids can substitute for a portion of the vitamin deficient in this patient?
From what amino acid can it be syntheiszied?
What are its functions?
Can be synthesized from tryptophan in 60:1 ratio
Coenzymes – as nicotinamide adenine dinucleotide (NAD & NADP) – in redox reactions, ATP synthesis & ADP-ribose transfer reactions
Large doses – anti-hyperlipidemic agent
Describe Niacin deficiency. What clinical manifestations?
What happens in late and early stages?
What is Hartnup's Disease?
Pellegra – photosensitive dermatitis; symmetrical lesions on parts of body exposed to sun (typically not the face); Casal’s necklace
3 D’s – dermatitis, diarrhea, dementia (death)
In late stages, encephalopathy of pellagra may occur: identical to Wernicke’s encephalopathy but responds to niacin supplementation; early characteristics are depression, apprehension, insomnia, headaches and dizziness; later signs include tremulous movements or rigidity of the limbs ending with paresis; dermatosis of niacin deficiency assists in differential diagnosis
Hartnup’s syndrome autosomal recessive disorder characterized by impaired synthesis of niacin from tryptophan resulting in pellagra-like symptoms
A 69-year-old edentulous, alcoholic man, who lives alone is admitted to the hospital for evaluation of a shoulder wound that is not healing well. On physical examination, numerous ecchymoses are noted on the posterior aspects of his legs and thighs. Careful examination of his skin reveals minute hemorrhages around hair follicles and splinter hemorrhages in the nail beds. Laboratory examination is remarkable for a hemoglobin of 10 g/dL; no other hematologic abnormalities are noted. Which of the following is the most appropriate therapy for this disorder?
a. Factor VIII
c. Vitamin B12
d. Vitamin C
e. Vitamin K
Describe Vitamin C. Name?
Humans, some primates, bats & guinea pigs – only mammals unable to synthesize vitamin C
Scurvy described as far back in history as Ancient Egypt, Greece & Rome
Coenzyme in redox reactions
Coenzyme for prolyl 4/3 hydoxylase (collagen hydroxylation)
...involved in post-translational modification of collagen - involved in x-linked formation
What will an ascorbic acid deficiency lead to?
Cardinal symptoms result from defects in collagen formation
Signs include petechiae, perifollicular hemorrhages, inflamed & bleeding gums, joint effusions, arthralgia, impaired wound healing; depression, weakness
Neurologic & hormonal signs not observed until very late – brain & adrenal pools relatively protected
Manifests as scurvy
- Mesenchymal symptoms result from defects in connective tissue formation
- Hemorrhagic manifestations: bleeding into joints, peritoneal cavity and/or pericardial sac
0 Inflammation and bleeding of the gingiva early sign of deficiency
- In infants, deficiency may result in bone abnormalities including impaired bone growth and disturbed ossification
A 72-year-old man presents to the hospital with a several week history of fatigue. Physical examination is remarkable for severe pallor. Neurologic examination reveals poor short-term memory and decreased vibratory sense in his legs. An ECG shows changes consistent with the presence of cardiac ischemia. The hemoglobin level is 4.1 g/dL, with a mean corpuscular volume of 105 μm3, a white cell count of 3100 per mm3 and a platelet count of 55,000 per mm3. The peripheral blood smear shows hypersegmentation of neutrophils, marked anisocytosis, poikilocytosis with some large oval erythrocytes, and basophilic stippling. Which of the following metabolic responses is most specific for the vitamin deficiency affecting this patient?
a. Decreased blood delta- aminolevulinic acid (ALA)
b. Decreased transketolase activity in erythrocytes
c. Decreased urinary homocysteine
d. Increased urinary methylmalonate (MMA)
e. Lactic acidosis
Describe Folic Acid.
What is its role?
Coenzyme for one-carbon (methyl group) transfer reactions – most significantly purine & pyrimidine synthesis & methylation of transfer RNA: thymidylate synthetase
Some anti-proliferative drugs work by blocking folate activity
Describe Folate metatbolism.
What are the folate-associated enzymes?
Which are the two most important?
Methylene THF reductase
(AKA homocysteine methyltransferase)
Two most important:
-methionine synthase (AKA homocysteine methyltransferase)
What causes and characterizes folic acid deficiency?
- Deficiency caused by inadequate intake, inadequate absorption, increased requirements, ie, fetal growth, or used folic acid antagonists, ie, methotrexate
- Primary characteristic megaloblastic anemia; ineffective hematopoeisis results in anemia, leucopenia and thrombopenia
- Symptoms of megaloblastic anemia include weakness, dyspnea, sore tongue, irritability and forgetfulness, anorexia, headache and palpitations; also occur with B12 deficiency
What is folate necessary to synthesize?
What is a major source of folate?
Describe the reduction of methylene THF to methyl THF.
How can methyl THF get demethylated back to THF?
What happens if Vitamin B12 is deficient?
1. Folate necessary for purine and thymidylate synthesis
2. Major source of folate for body tissues is tetrahydrofolate (THF)
3. Reduction of methylene THF to methyl THF is irreversible
4. Only metabolic role of methyl THF is methylation of homocysteine to methionine, therefore, only way methyl THF to get demethylated back to THF is through methionine synthase activity (B12 is coenzyme)
5. If vitamin B12 is deficient, methyl THF accumulates in cell and THF decreases – along with purine and DNA synthesis
Defective DNA & RNA synthesis – decrease in nucleotide & purine synthesis
Megaloblastic anemia – nucleated RBC with dispersed chromatin
Ineffective hematopoiesis results in premature cell death
Symptoms similar to iron deficiency anemia – fatigue, etc; bright red sore tongue may be present
What would happen if thymidylate synthase was inhibited?
What can inhibit dihydrofolate reducataase?
Thymidylate synthase- inhibition of this step leads to megaloblastic anemia; by folate or B12 deficiency, also inhibited by 5-fluoruracil (cancer drug)
Dihydrofolate reductase- inhibited by methotrexate
Describe Vitamin B12.
What is unique about this vitamin?
What is it a co-enzyme for?
Vitamin B12 – Cobalamin
Only vitamin with non-organic component – cobalt atom
Coenzyme for one-carbon transfers: methionine synthase &
methylmalonyl-CoA mutase (methylmalonyl CoA to succinyl CoA)
Deficiency symptoms often indistinguishable from folate deficiency
What is the defining test for B12 deficiency vs folate?
increased MMA in urine
Describe Vit. B12 deficiency.
May present in vegan diet
- Patients with hypochlorhydria, eg, in the elderly or in post-gastrectomy patients, may have impaired absorption
- Pernicious anemia is result of lack of intrinsic factor; lack of intrinsic factor may result from autoantibodies produced against the protein or congenital form of impaired intrinsic factor secretion
- Deficiency results in inhibition of methionine synthase leading to impaired nucleic acid (DNA) synthesis & increase in plasma homocysteine; results in megaloblastic anemia, as described for folate, or hyperhomocysteinemia
- Elevated homocysteine levels in the blood may be risk factor for vascular disease
- Neuropathy associated with vitamin B12 deficiency related to changes in methylation ratio in brain tissues
What happens if you don't have B12 or folate in adequate amounts?
if don't have B12 or folate in adequate amounts stop cycle at homocystine. increased homocysteine in the plasma
What are the enzymes associated with methionine metabolism?
(AKA homocysteine methyltransferase)
various methyltransferase enzymes
protein coming in, aa …methionine..donates its methyl group to bunch of receptors.. homocysteine can become cysteine or remethylated to become methionine.. (methionine synthase is linkage between Vit B12 and folate acid metabolism with regard to methionine synthesis or remethylation)
What does methotrexate do?
What does it lead to? Why?
What builds up in the blood?
methotrexate blocks enzyme DHF… folic a doesn't get into cycle and DNA syn. is slowed
5-fluoro urail also blocks thymadiyl synthase
both drugs work directly on a nutrient . block those 2 and decrease DNA synthesis
leads to megaloblastic anemia
if you do not have B12 or low in B12 methyanine synthase blocked so also get mega. anemia bc THF can’t come back to regenerate… can’t cycle back
if both folate deficiency and B12 def. can have meg. anemia or hyperhomocysteinemia…homocys. builds up in the blood
A cardiovascular researcher is conducting a study to evaluate the relationship between folate levels and CVD. The results of the study show that persons with lower folate levels have twice the risk of CVD mortality than do those with higher folate levels. Which of the following enzymes is most closely related to the role of folate in lowering the risk of CVD?
a. Dihydrofolate reductase
b. Glycinamide ribonucleotide transformylase
c. Homocysteine methyltransferase (same as methionine synthase)
d. Ribonucleotide reductase
e. Thymidylate synthase
If deficient what two main things can occur?
Describe Vitamin B12? What can occur if deficient? Why?
Defective DNA & RNA synthesis
neural tube defects – experimental studies in animals, epidemiologic studies in humans; since 1998 grain products enriched with folate in US
Hyperhomocysteinemia – atherogenic, hypertensive & procoagulant effects; controversy remains over significance for CVD
Defective DNA & RNA synthesis
Megaloblastic anemia due to decreased B12 absorption – also called Pernicious Anemia – result of loss of intrinsic factor secretion (due to atrophic gastritis, achlorhydria of ageing, gastric bypass surgery); easily corrected