chase findley, msiv. vitamins, fat soluble, 94 vitamins a, d, e, k absorption dependent on ileum...

Chase Findley, MSIVChase Findley, MSIV

Vitamins, Fat Soluble, 94Vitamins, Fat Soluble, 94

Vitamins Vitamins A, D, E, KA, D, E, KAbsorption dependent on ileum and Absorption dependent on ileum and

pancreaspancreasAccumulate in body fat, more potential for Accumulate in body fat, more potential for

toxicitytoxicityFat malabsorption Fat malabsorption conditions may cause conditions may cause

deficiencydeficiency○ Cystic fibrosis, celiac sprueCystic fibrosis, celiac sprue, mineral oil intake, mineral oil intake


Vitamin A (Retinol)Vitamin A (Retinol)FoundFound: : liverliver, leafy vegetables, leafy vegetablesFunctionsFunctions: antioxidant, constituent of : antioxidant, constituent of retinal retinal

visual pigmentvisual pigmentDeficiencyDeficiency: : night blindnessnight blindness, dry skin, dry skinExcessExcess: head ache, arthralgias, fatigue, skin : head ache, arthralgias, fatigue, skin

changes, sore throat, alopeciachanges, sore throat, alopeciaTeratogenic: cleft palate, cardiac problemsTeratogenic: cleft palate, cardiac problemsRemember Remember bear hunter bear hunter who eats liver!who eats liver!


Vitamin DVitamin DFoundFound: Fortified milk: Fortified milkFunctionFunction: Increases : Increases intestinal absorption of intestinal absorption of

calcium and phosphatecalcium and phosphate, bone resorption, bone resorptionDeficiencyDeficiency: : Rickets (children), osteomalacia Rickets (children), osteomalacia

(adults)(adults), hypocalcemic tetany, hypocalcemic tetanyExcessExcess: : HypercalcemiaHypercalcemia, hypercalciuria, loss , hypercalciuria, loss

of appetite, stupor. (Seen in of appetite, stupor. (Seen in sarcoidosissarcoidosis))


Vitamin D, continuedVitamin D, continuedD2D2

○ Found in plants, pharmacological formFound in plants, pharmacological formD3D3

○ Found in milk, Found in milk, formed in sun exposed skinformed in sun exposed skin25-OH D3 25-OH D3

○ Storage formStorage form1,25-(OH)2D3 (Calcitriol)1,25-(OH)2D3 (Calcitriol)

○ Active formActive form


Vitamin EVitamin EFound:Found: Vegetable oils, nuts, leafy Vegetable oils, nuts, leafy

vegetablesvegetablesFunctionFunction: : AntioxidantAntioxidant, protects RBC’s and , protects RBC’s and

membranes from free radical damagemembranes from free radical damageDeficiencyDeficiency: Increased fragility of RBC’s, : Increased fragility of RBC’s,

muscle weakness, neurodysfunctionmuscle weakness, neurodysfunction


Vitamin KVitamin KFoundFound: Leafy vegetables, some fruits: Leafy vegetables, some fruitsFunctionFunction: Necessary for : Necessary for synthesis of synthesis of

clotting factors II, VII, IX, X, protein C and Sclotting factors II, VII, IX, X, protein C and S, , catalyzes catalyzes γγ-carboxylation of glutamic acid -carboxylation of glutamic acid residuesresidues

DeficiencyDeficiency: : HemorrhageHemorrhage with increased PT, with increased PT, PTT, normal bleeding time.PTT, normal bleeding time.○ Neonatal hemorrhage, give Vitamin K at birthNeonatal hemorrhage, give Vitamin K at birth○ WarfarinWarfarin antagonizes Vitamin K antagonizes Vitamin K

Vitamins, Water Soluble, Vitamins, Water Soluble, 9494 Vitamins Vitamins B1 (thiamine), B2 (riboflavin), B3 B1 (thiamine), B2 (riboflavin), B3

(niacin), B5 (pantothenic acid), B6 (niacin), B5 (pantothenic acid), B6 pyridoxine, B12 (cobalamin), C (ascorbic pyridoxine, B12 (cobalamin), C (ascorbic acid, biotin, folateacid, biotin, folate

All except B12 and folate wash out from All except B12 and folate wash out from body, low risk of toxicitybody, low risk of toxicity

Vitamins, Water Soluble, Vitamins, Water Soluble, 9494 Vitamin B1 (thiamine)Vitamin B1 (thiamine)

FunctionFunction: Component of : Component of thiamine thiamine pyrophosphate, pyrophosphate, cofactor in:cofactor in:○ Pyruvate dehydrogenase (Pyruvate dehydrogenase (glycolysisglycolysis))○ αα-ketoglutarate dehydrogenase (-ketoglutarate dehydrogenase (TCA cycleTCA cycle))○ Transketolase (Transketolase (HMP shuntHMP shunt) ) ○ Branched chain amino acid dehydrogenaseBranched chain amino acid dehydrogenase

Vitamins, Water Soluble, Vitamins, Water Soluble, 9595 Vitamin B1 (thiamine), continuedVitamin B1 (thiamine), continued

DeficiencyDeficiency: : ○ Wernike-Korsakoff syndromeWernike-Korsakoff syndrome

Seen in malnutrition, Seen in malnutrition, alcoholismalcoholismConfusion, ophthalmoplegia, confabulationConfusion, ophthalmoplegia, confabulation

○ Beriberi (dry)Beriberi (dry)PolyneuritisPolyneuritis, symmetrical muscle wasting, symmetrical muscle wasting

○ Beriberi (wet)Beriberi (wet)High-output cardiac failure High-output cardiac failure (dilated cardiomyopathy) (dilated cardiomyopathy)

edemaedema

Vitamins, Water Soluble, Vitamins, Water Soluble, 9595 Vitamin B2 (riboflavin)Vitamin B2 (riboflavin)

FunctionFunction: : Cofactor in oxidation and Cofactor in oxidation and reduction reduction (FAD, FMN) B2=2 ATP(FAD, FMN) B2=2 ATP

DeficiencyDeficiency: : CheilosisCheilosis, corneal , corneal vascularizationvascularization

Vitamins, Water Soluble, Vitamins, Water Soluble, 9595 Vitamin B3 (niacin)Vitamin B3 (niacin)

FunctionFunction: Constituent of : Constituent of NAD, NADPNAD, NADP, used in , used in redoxredox reactions, B3=3 ATP reactions, B3=3 ATP

Derived from tryptophan, requires B6 for Derived from tryptophan, requires B6 for synthesissynthesis

DeficiencyDeficiency: : Pellagra (diarrhea, dermatitis, Pellagra (diarrhea, dermatitis, dementia)dementia), glossitis, glossitis○ Hartnup disease (decreased tryptophan Hartnup disease (decreased tryptophan

absorption)absorption)○ Malignant carcinoid syndrome (increased Malignant carcinoid syndrome (increased

tryptophan metabolismtryptophan metabolism○ INH (anti-TB) (decreased B6)INH (anti-TB) (decreased B6)

Vitamins, Water Soluble, Vitamins, Water Soluble, 9595 Vitamin B3 (niacin), continuedVitamin B3 (niacin), continued

Clinical useClinical use: : Treatment of hyperlipidemia Treatment of hyperlipidemia (decrease LDL, increase HDL)(decrease LDL, increase HDL)

ExcessExcess: : Facial flushingFacial flushing, treat with aspirin, treat with aspirin

Vitamins, Water Soluble, Vitamins, Water Soluble, 9595 Vitamin B5 (pantothenate) Vitamin B5 (pantothenate)

FunctionFunction: Component of : Component of CoACoA (cofactor in (cofactor in acyl transfers) and acyl transfers) and fatty acid synthasefatty acid synthase

DeficiencyDeficiency: Dermatitis, enteritis, alopecia, : Dermatitis, enteritis, alopecia, adrenal insufficiencyadrenal insufficiency

Vitamins, Water Soluble, Vitamins, Water Soluble, 9595 Vitamin B6 (pyridoxine)Vitamin B6 (pyridoxine)

FunctionFunction: Converted to : Converted to pyridoxal, pyridoxal, phosphatephosphate, cofactor in , cofactor in transaminationtransamination (ALT/AST), (ALT/AST), decarboxylationdecarboxylation reactions, reactions, glycogen phosphorylaseglycogen phosphorylase, , heme synthesisheme synthesis

Required for Required for synthesis of B3 (niacin)synthesis of B3 (niacin)DeficiencyDeficiency: Convulsions, hyperirritability, : Convulsions, hyperirritability,

peripheral neuropathyperipheral neuropathy○ May be induced by INH, OCP’sMay be induced by INH, OCP’s

Vitamins, Water Soluble, Vitamins, Water Soluble, 9696 Vitamin B12 (cobalamin)Vitamin B12 (cobalamin)

FoundFound: : Only in animal productsOnly in animal products, synthesized , synthesized by microorganisms (large reserves in by microorganisms (large reserves in liverliver))

FunctionFunction: Cofactor for : Cofactor for homocysteine homocysteine methyltransferasemethyltransferase (transfers (transfers CH3CH3 groups) groups) and and methylmalonyl-CoA mutasemethylmalonyl-CoA mutase


Deficiency: Deficiency: ○ Macrocytic-megaloblastic anemiaMacrocytic-megaloblastic anemia○ Neurological symptomsNeurological symptoms

Irreversible if prolongedIrreversible if prolongedParesthesiasParesthesiasSub acute combined degenerationSub acute combined degeneration

- Posterior and lateral spinal columnsPosterior and lateral spinal columns


Causes of deficiencyCauses of deficiency○ Intestinal malabsorptionIntestinal malabsorption

Sprue, enteritis, Sprue, enteritis, fish tapewormfish tapeworm

○ Lack of intrinsic factorLack of intrinsic factorPernicious anemiaPernicious anemia

○ Absence of Absence of terminal ileum terminal ileum Crohn’s disease, surgicalCrohn’s disease, surgical

Schilling test Schilling test to detect etiology of deficiencyto detect etiology of deficiency

Vitamins, Water Soluble, Vitamins, Water Soluble, 9696 Folic AcidFolic Acid

FunctionFunction: Converted to : Converted to tetrahydrofolate tetrahydrofolate (THF)(THF), coenzyme used in , coenzyme used in 1-carbon 1-carbon transfer/methylationtransfer/methylation reaction. Used in reaction. Used in synthesis of synthesis of nitrogenous bases nitrogenous bases in DNA/RNAin DNA/RNA

DeficiencyDeficiency: : ○ Macrocytic-megaloblastic anemiaMacrocytic-megaloblastic anemia

Without neurological symptomsWithout neurological symptoms

○ Neural tube defectsNeural tube defectsPrevent with prenatal supplementsPrevent with prenatal supplements

Vitamins, Water Soluble, Vitamins, Water Soluble, 9696 Folic acid, continuedFolic acid, continued

DeficiencyDeficiency○ Much smaller liver stores than B12Much smaller liver stores than B12○ Most common US vitamin deficiencyMost common US vitamin deficiency

Especially in pregnancy, Especially in pregnancy, alcoholismalcoholism

○ Can be caused by Can be caused by phenytoinphenytoin, sulfonamides, , sulfonamides, methotrexatemethotrexate

Vitamins, Water Soluble, Vitamins, Water Soluble, 9797 BiotinBiotin

FunctionFunction: : Cofactor for carboxylation Cofactor for carboxylation enzymes, enzymes, pyruvate carboxylase, acetyl-CoA pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylasecarboxylase, propionyl-CoA carboxylase

Avidin (raw egg whites) binds biotin and Avidin (raw egg whites) binds biotin and prevents absorptionprevents absorption

DeficiencyDeficiency: Dermatitis, alopecia, enteritis.: Dermatitis, alopecia, enteritis.○ Antibiotic use or excessive raw eggsAntibiotic use or excessive raw eggs

Vitamins, Water Soluble, Vitamins, Water Soluble, 9797 Vitamin C (ascorbic acid)Vitamin C (ascorbic acid)

FoundFound: Fruits, vegetables: Fruits, vegetablesFunctionFunction: : AntioxidantAntioxidant, also:, also:

○ Facilitates Facilitates iron absorption iron absorption by keeping Fe in by keeping Fe in more absorbable Fe2+more absorbable Fe2+

○ Necessary for Necessary for hydroxylation of proline and hydroxylation of proline and lysine in collagen synthesislysine in collagen synthesis

○ Necessary for Necessary for dopamine dopamine ββ-hydroxylase -hydroxylase (converts dopamine to norepinephrine) (converts dopamine to norepinephrine)

Vitamins, Water Soluble, Vitamins, Water Soluble, 9797 Vitamin C (ascorbic acid)Vitamin C (ascorbic acid)

Deficiency:Deficiency: Scurvy Scurvy○ Swollen gums, bruising, anemia, poor wound Swollen gums, bruising, anemia, poor wound

healinghealing

Minerals, 98Minerals, 98

ZincZincFunctionFunction: Involved in activity of 100+ : Involved in activity of 100+

enzymes. Important in enzymes. Important in zinc finger zinc finger (transcription factor motif)(transcription factor motif)

DeficiencyDeficiency: : Delayed wound healingDelayed wound healing, , hypogonadism, decreased adult hair, hypogonadism, decreased adult hair, predisposes to alcoholic cirrhosispredisposes to alcoholic cirrhosis

Malnutrition, 98Malnutrition, 98

KwashiorkorKwashiorkorProteinProtein deficiency deficiencySkin lesionsSkin lesions, liver malfunction (fatty , liver malfunction (fatty

change), change), edemaedema, anemia, anemia

Malnutrition, 98Malnutrition, 98

MarasmusMarasmusTotal calorie Total calorie deficiencydeficiencyTissue and muscle wastingTissue and muscle wasting, loss of , loss of

subcutaneous fat, edemasubcutaneous fat, edema

Ethanol Metabolism, 98Ethanol Metabolism, 98

Alcohol dehydrogenase operates via Alcohol dehydrogenase operates via zero-order zero-order kineticskinetics

NAD+ NAD+ is limiting reagentis limiting reagent Fomepizole inhibits alcohol dehydrogenaseFomepizole inhibits alcohol dehydrogenase Disulfiram inhibits acetaldehyde dehydrogenaseDisulfiram inhibits acetaldehyde dehydrogenase

Universal Electron Acceptors, 101 NAD+, NADP+

Require Vitamin B3 (niacin) for productionNAD+

○ Catabolic processes, carry reducing equivalents as NADH

NADP+ ○ Anabolic processes, supply reducing equivalents

as NADPH○ NADPH also used in respiratory burst, P-450

FAD+Requires Vitamin B2 (riboflavin) for production

Metabolism, 101Metabolism, 101

ATP Production (Glycolysis)Hydrolysis drives energetically unfavorable

reactionsAerobic metabolism

○ Produces 32 (heart/liver) 30 (muscle) ATP per glucose

Anaerobic metabolism○ Produces 2 ATP per glucose

Hexokinase Vs. Hexokinase Vs. Glucokinase, 101Glucokinase, 101 First step of glycolysis First step of glycolysis is glucose to G6Pis glucose to G6P Reaction catalyzed by Reaction catalyzed by hexokinase or hexokinase or

glucokinaseglucokinase, 1, 1stst regulation point regulation point HexokinaseHexokinase

UbiquitousUbiquitous, high affinity (low Km), low capacity , high affinity (low Km), low capacity (low Vmax), (low Vmax), feedback inhibited by productfeedback inhibited by product

GlucokinaseGlucokinaseLiver and pancreas Liver and pancreas ββ-cells-cells, low affinity (high Km) , low affinity (high Km)

and high capacity (high Vmax) and high capacity (high Vmax) induced by induced by insulin, sequesters excess glucose in liver.insulin, sequesters excess glucose in liver.

Hexokinase Vs. Hexokinase Vs. Glucokinase, 101Glucokinase, 101

Glycolytic Enzyme Glycolytic Enzyme Deficiency, 103Deficiency, 103 Deficiency of Deficiency of pyruvate kinase pyruvate kinase or or

phosphoglucose isomerase phosphoglucose isomerase Inability to maintain Na+-K+ ATPaseInability to maintain Na+-K+ ATPase RBC swelling, lysisRBC swelling, lysis Hemolytic anemiaHemolytic anemia

RBC’s depend solely on glycolysis of RBC’s depend solely on glycolysis of glucose for metabolismglucose for metabolism

Pyruvate dehydrogenase Pyruvate dehydrogenase Deficiency, 103Deficiency, 103 Back up of substrate (pyruvate, alanine), Back up of substrate (pyruvate, alanine),

leads to leads to lactic acidosislactic acidosis Congenital and acquired (B1 deficiency) Congenital and acquired (B1 deficiency)

formsforms Neurologic deficitsNeurologic deficits Treat by increasing intake of ketogenic Treat by increasing intake of ketogenic

nutrients (high fat, lysine, leucine)nutrients (high fat, lysine, leucine)

Pyruvate Metabolism, Pyruvate Metabolism, 103103Alanine carries AA to Alanine carries AA to

liver from muscleliver from muscle

Oxaloacetate used to Oxaloacetate used to

in TCA cycle or gluco-in TCA cycle or gluco-

neogenesisneogenesis

Transition from glyco-Transition from glyco-

lysis to TCA cyclelysis to TCA cycle

End of anaerobicEnd of anaerobic

glycolysisglycolysis

Cori Cycle, 103Cori Cycle, 103 Muscle Muscle andand RBC’s RBC’s generate generate lactatelactate via via

anaerobic glycolysisanaerobic glycolysis LactateLactate sent to sent to liverliver to be used in to be used in

gluconeogenesis gluconeogenesis Glucose can then be sent back and used Glucose can then be sent back and used

by muscle and RBC’sby muscle and RBC’s Loss of 4 ATP/CycleLoss of 4 ATP/Cycle

HMP Shunt, 105Produces NADPH Produces NADPH for fatty acid and steroid synthesis, and for fatty acid and steroid synthesis, and

glutathione reduction in RBC’sglutathione reduction in RBC’s

Oxidative (irreversible)Oxidative (irreversible)

and non-oxidative and non-oxidative

(reversible) phases(reversible) phases

Occurs in lactatingOccurs in lactating

mammary glands, liver,mammary glands, liver,

adrenal cortex, RBC’sadrenal cortex, RBC’s

Respiratory Burst, 105Respiratory Burst, 105 Produces reactive oxygen (HOCl) species for

immune response Occurs in neutrophils, macrophages Involves membrane-bound NADPH oxidase

(deficient in chronic

granulomatous disease)

Glucose-6-Phosphate Dehydrogenase Deficiency, 106 G6PD produces NADPHG6PD produces NADPH, necessary to , necessary to

keep keep glutathione reducedglutathione reduced, which detoxifies , which detoxifies free radicals/peroxidesfree radicals/peroxides

Decreased NADPH Decreased NADPH leads to leads to hemolytic hemolytic anemia anemia due to damage from oxidizing due to damage from oxidizing agentsagents

X-linked recessive, X-linked recessive,

most common most common

enzyme deficiencyenzyme deficiency

Glucose-6-Phosphate Glucose-6-Phosphate Dehydrogenase Deficiency, Dehydrogenase Deficiency, 106106 Oxidizing agents include fava beans, Oxidizing agents include fava beans,

sulfanamides, primaquine, anti-TB drugssulfanamides, primaquine, anti-TB drugs Affected individuals have malarial Affected individuals have malarial

resistanceresistance Heinz bodiesHeinz bodies

Altered precipitated hemoglobin in RBC’sAltered precipitated hemoglobin in RBC’s

Bite CellsBite CellsFrom phagocytic removal of Heinz bodies by From phagocytic removal of Heinz bodies by

spleenspleen

Glucose-6-Phoshate Glucose-6-Phoshate Dehydrogenase Deficiency, Dehydrogenase Deficiency, 106106 Heinz bodies, bite cellsHeinz bodies, bite cells

Disorders of Fructose Metabolism, 106 Fructose intoleranceFructose intolerance

Hereditary deficiency of Hereditary deficiency of aldolase Baldolase BAutosomal recessiveAutosomal recessiveFructose-1-phosphate accumulatesFructose-1-phosphate accumulates, leading to , leading to

decrease in available phosphate, inhibits decrease in available phosphate, inhibits glycogenolysis and gluconeogenesisglycogenolysis and gluconeogenesis

Hypoglycemia, jaundice, cirrhosis, Hypoglycemia, jaundice, cirrhosis,

vomitingvomitingDecrease intake of fructose and Decrease intake of fructose and

sucrosesucrose

Disorders of Fructose Disorders of Fructose Metabolism, 106Metabolism, 106 Essential fructosuriaEssential fructosuria

Defect in fructokinaseDefect in fructokinaseAutosomal recessiveAutosomal recessiveBenign, asymptomaticBenign, asymptomaticFructose in blood and urineFructose in blood and urine

Disorders of Galactose Disorders of Galactose Metabolism, 107Metabolism, 107 Classic galactosemiaClassic galactosemia

Absence of galactose-1-phosphate Absence of galactose-1-phosphate uridyltransferaseuridyltransferase. .

Autosomal recessiveAutosomal recessiveToxic damage from Toxic damage from galactitolgalactitolFailure to Failure to thrive, jaundice, thrive, jaundice,

hepatomegaly, infantile hepatomegaly, infantile

cataracts, mental retardationcataracts, mental retardationExclude galactose and lactoseExclude galactose and lactose

from dietfrom diet

Disorders of Galactose Disorders of Galactose Metabolism, 107Metabolism, 107 Galactokinase deficiencyGalactokinase deficiency

Autosomal recessiveAutosomal recessiveGalactitolGalactitol accumulates if galactose is present in accumulates if galactose is present in

dietdietGalactose appears in blood Galactose appears in blood

and urine, infantile cataracts,and urine, infantile cataracts,

failure to track objects, lack offailure to track objects, lack of

social smilesocial smile

Lactase Deficiency, 107Lactase Deficiency, 107

Age dependent or hereditary Age dependent or hereditary lactose lactose intolerance intolerance due to due to loss of brush-border loss of brush-border enzymeenzyme

Bloating, cramps, Bloating, cramps, osmotic diarrheaosmotic diarrhea Avoid dairy products, lactase Avoid dairy products, lactase

supplementssupplements

Transport of alanine and Transport of alanine and glutamine, 108glutamine, 108 Glucose in muscle is oxidized to pyruvate, Glucose in muscle is oxidized to pyruvate,

producing energyproducing energy Pyruvate is transaminated to alanine, travels to Pyruvate is transaminated to alanine, travels to

liver, providing nitrogen for urea cycle, and carbon liver, providing nitrogen for urea cycle, and carbon for for gluconeogenesisgluconeogenesis

Hyperammonemia, 108Hyperammonemia, 108

Acquired (liver disease) or hereditary Acquired (liver disease) or hereditary (urea enzyme deficiencies) (urea enzyme deficiencies)

Results in excess NH4+, depletes Results in excess NH4+, depletes αα--ketoglutarate, inhibits TCA cycleketoglutarate, inhibits TCA cycle

Tremor, slurring speech, somnolence,Tremor, slurring speech, somnolence, vomiting, cerebral edema, blurred visionvomiting, cerebral edema, blurred vision

Treat with benzoate, phenylbutyrateTreat with benzoate, phenylbutyrate

Ornithine Ornithine Transcarbamoylase Transcarbamoylase Defiency, 108Defiency, 108 Most common urea cycle disorder X-linked recessive Interferes with elimination of ammonia May present in first days of life Excess carbamoyl phosphate converted

to orotic acid Orotic acid in blood and urine,

decreased BUN, hyperammonemia

Phenylketonuria, 109Phenylketonuria, 109

Decreased phenylalanine hydroxylase Decreased phenylalanine hydroxylase or tetrahydrobiopterin cofactor. or tetrahydrobiopterin cofactor.

Tyrosine can not be synthesized, Tyrosine can not be synthesized, becomes essentialbecomes essential

Autosomal recessiveAutosomal recessive Increased phenylalanine Increased phenylalanine

leads to excess leads to excess

phenylketones in urine.phenylketones in urine.

Phenylketonuria, 109Phenylketonuria, 109

Mental retardation, growth retardation, Mental retardation, growth retardation, seizures, fair skin, eczema, musty body seizures, fair skin, eczema, musty body odorodor

Treat by increased tyrosine and Treat by increased tyrosine and decreased phenylalanine in dietdecreased phenylalanine in diet

Maternal PKU, (deficiency in pregnancy) Maternal PKU, (deficiency in pregnancy) causes mental retardation, growth causes mental retardation, growth retardation, microcephaly, heart defectsretardation, microcephaly, heart defects

Alkaptonuria, 109Alkaptonuria, 109 Congenital Congenital deficiency of homogentisic acid deficiency of homogentisic acid

oxidaseoxidase in degradative pathway of in degradative pathway of tyrosinetyrosine Autosomal recessiveAutosomal recessive Dark connective tissue, pigmented sclera, Dark connective tissue, pigmented sclera,

urine turns black on standingurine turns black on standing, arthralgias, arthralgias

Albinism, 109Albinism, 109 Congenital defect in either:Congenital defect in either:

TyrosinaseTyrosinase○ Inability to synthesize Inability to synthesize melaninmelanin from tyrosine from tyrosine○ Autosomal recessiveAutosomal recessive

Tyrosine transportersTyrosine transporters○ Variable inheritance,Variable inheritance,

locus heterogenity locus heterogenity ○ Decreased availability of Decreased availability of

tyrosine for melanin tyrosine for melanin synthesissynthesis

Albinism, 109Albinism, 109

Can result from lack of migration of neural crest cells.

Increased risk of skin cancer

Homocystinuria, 100Homocystinuria, 100 Autosomal recessive 3 forms, all result in excess homocysteine 1. Cystathionine synthase deficiency 2. Decreased affinity of

cystathionine synthase for

pyridoxal phosphate (treat

with increased B6 in diet) 3. Homocysteine

methyltransferase deficiency

Homocystinuria, 110Homocystinuria, 110

Cystine becomes essential Increased homocysteine in urine, mental

retardation, osteoporosis, tall stature, kyphosis, lens subluxation, atherosclerosis (MI and stroke)

Cystinuria, 110Cystinuria, 110 Hereditary defect of Hereditary defect of renal tubular amino renal tubular amino

acid transporteracid transporter for cysteine, ornithine, for cysteine, ornithine, lysine, arginine in lysine, arginine in proximal convoluted proximal convoluted tubule.tubule.

Excess cystine in precipitates, forms Excess cystine in precipitates, forms cystine kidney stonescystine kidney stones..

Autosomal recessiveAutosomal recessive Treat with Treat with acetazolamideacetazolamide to to

alkalinize urine.alkalinize urine.

Maple Syrup Disease, Maple Syrup Disease, 110110 Blocked degradation of Blocked degradation of branched amino branched amino

acids (Ile, Leu, Val)acids (Ile, Leu, Val), due to decreased α-ketoacid dehydrogenase.

Results in Results in accumulation accumulation ofof αα-ketoacids -ketoacids in bloodin blood

Severe CNS defects, mental retardation, Severe CNS defects, mental retardation, death.death.

Urine smells like maple syrupUrine smells like maple syrup

Adenosine Deaminase Deficiency, 111 Excess ATP and dATP imbalances

nucleotide pool (feedback inhibition of ribonucleotide reductase)

Prevents DNA synthesis Decreased lymphocyte count Major cause of severe combined

immunodeficiency disorder

Lesch-Nyhan Syndrome, Lesch-Nyhan Syndrome, 111111 Absence of HGPRT leads to defective

purine salvage pathway Excess uric acid production X-linked recessive

Mental retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis

Orotic aciduria, 111Orotic aciduria, 111

Inability to convert orotic acid UMP in de novo pyrimidine synthesis pathwayDefect in orotic acid

phosphoribosetransferase or orotidine 5’-phosphate decarboxylase

Autosomal recessive Increased orotic acid in urine,

megaloblastic anemia, failure to thrive Treat with oral uridine

Insulin, 112Insulin, 112

Synthesized in pancreas β cells Released in response to ATP from

glucose metabolism (depolarizing K+ channels)

Anabolic effects:Increases glucose transport, glycogen

synthesis and storage, triglyceride synthesis and storage, protein synthesis

Increased Na+ retention, cellular K+ uptake


Inhibits glucagon Inhibits glucagon release by pancreas release by pancreas αα cellscells

Insulin Insulin dephosphorylatesdephosphorylates Serum C-peptide only present with Serum C-peptide only present with

endogenous proteinendogenous proteinLack of C-peptide indicated exogenous Lack of C-peptide indicated exogenous

insulin useinsulin use


Insulin moves glucose into cells Some cells do not need insulin, use a

glucose transporterGLUT1: RBC’s, brainGLUT2: β islet cells, liver, kidneyGLUT4: (insulin sensitive) adipose tissue,

skeletal muscle

Glycogen, 112 Branches: Branches: αα (1,6) bonds (1,6) bonds Linkages: Linkages: αα (1,4) bonds (1,4) bonds Glycogen Glycogen phosphorylatesphosphorylates Skeletal muscleSkeletal muscle

Glycogen Glycogen undergoes glycogenolysis to form undergoes glycogenolysis to form glucoseglucose, which is , which is metabolized during exercisemetabolized during exercise

HepatocytesHepatocytesGlycogen is Glycogen is storedstored and undergoes and undergoes

glycogenolysis to glycogenolysis to maintain blood glucose levelsmaintain blood glucose levels

Glycogen Storage Disease, 113

DiseaseDisease Findings Deficient enzyme

Von Gierke’s (I) Severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate, hepatomegaly

Glucose-6-phosphate

Pompe’s (II) Cardiomegaly Lysosomal α-1,4 glucosidase (acid maltase)

Cori’s (III) Milder type I, normal blood lactate levels

Debranching enzyme

McArdle’s (V) Increased glycogen in muscle, muscle cramps, myoglobinuria

Skeletal muscle glycogen phosphorylase

All cause abnormal glycogen metabolism and accumulation All cause abnormal glycogen metabolism and accumulation within cellswithin cells

Ketone Bodies, 115Ketone Bodies, 115

In liver, In liver, fatty acids fatty acids and and amino acids amino acids are are metobolized to metobolized to acetoacetateacetoacetate and and ββ--hydroxybutyratehydroxybutyrate for use in muscle and for use in muscle and brainbrain

Produced in response to Produced in response to starvation, starvation, alcoholismalcoholism

Breath smells like acetoneBreath smells like acetone

Metabolic Fuel Use, 116Metabolic Fuel Use, 116

ExerciseExercise11stst (seconds) (seconds) Stored ATPStored ATP, creatine , creatine

phosphate, phosphate, anaerobic glycolysisanaerobic glycolysis22ndnd (minutes) + (minutes) +Oxidative phosphorylationOxidative phosphorylation33rdrd (hours) (hours) Glycogen and FFA oxidationGlycogen and FFA oxidation, ,

glucose conservedglucose conserved


Fasting and starvationFasting and starvationPreserve glucose for brain and RBC’sPreserve glucose for brain and RBC’sDays 1-3Days 1-3

○ Hepatic glycogenolysis Hepatic glycogenolysis and glucose releaseand glucose release○ Adipose release of free fatty acidsAdipose release of free fatty acids, used by , used by

muscle and liver (in place of glucose)muscle and liver (in place of glucose)○ Hepatic gluconeogenesis Hepatic gluconeogenesis from peripheral from peripheral

lactate and alanine, adipose tissuelactate and alanine, adipose tissue


Fasting and starvationFasting and starvationAfter 3 daysAfter 3 days

○ Muscle protein used for hepatic formation of Muscle protein used for hepatic formation of ketone bodies ketone bodies for brain and heartfor brain and heart

Several daysSeveral days○ Ketone bodies become main energy source Ketone bodies become main energy source

for brainfor brain

○ Survival time determined by Survival time determined by fat storesfat stores

Lipid Transport Lipid Transport Enzymes, 117Enzymes, 117 Pancreatic lipasePancreatic lipase

Degradation of Degradation of dietary lipase in small dietary lipase in small intestineintestine

Lipoprotein lipaseLipoprotein lipaseDegradation of Degradation of TG in chylomicrons and TG in chylomicrons and

VLDLVLDL Hepatic TG lipaseHepatic TG lipase

Degradation of Degradation of TG in IDLTG in IDL Hormone sensitive lipaseHormone sensitive lipase

Degradation of Degradation of TG in adipocytesTG in adipocytes

Cholesterol Synthesis, 116 Rate limiting step catalyzed by HMG-CoA

reductase Enzyme inhibited by statins

2/3 plasma cholesterol is esterified by lecithin-cholesterol

acyltransferase (LCAT) Cholesterol ester transport

protein (CETP) mediates

transfer of cholesterol esters to

lipoprotein particles

Essential Fatty Acids, Essential Fatty Acids, 116116 Can not be synthesized, must be in dietCan not be synthesized, must be in diet Linoleic and linolenic acidsLinoleic and linolenic acids Arachidonic acid, if linoleic acid is Arachidonic acid, if linoleic acid is

absentabsent Necessary for synthesis of eicosandoidsNecessary for synthesis of eicosandoids

Lipoprotein Functions, Lipoprotein Functions, 118118 Lipoproteins are composed of varying Lipoproteins are composed of varying

proportions of proportions of cholesterol, triglycerides, cholesterol, triglycerides, phospholipidsphospholipids

LDLLDL transports cholesterol from transports cholesterol from liver to liver to tissuestissues

HDLHDL transports cholesterol from transports cholesterol from tissues tissues to liverto liver

Lipoprotein Functions, Lipoprotein Functions, 118118 Chylomicron

Delivers dietary TG’s to tissueDelivers cholesterol to liver as chylomicron

remnants (depleted of triacylglycerols)Secreted by intestinal epithelial cellsB-48, A-IV, C-II, E

Familial dyslipidemia I○ Increased chylomicrons○ Elevated TG, cholesterol○ Lipoprotein lipase deficiency or altered

apolipoprotein C-II

Lipoprotein, 118Lipoprotein, 118 VLDLVLDL

Delivers Delivers hepatic TG’s to tissuehepatic TG’s to tissue Secreted by Secreted by liverliver B-100, C-II, EB-100, C-II, E

HypertriglyceridemiaHypertriglyceridemia○ Increased VLDLIncreased VLDL○ Elevated TGElevated TG○ Hepatic overproduction of VLDLHepatic overproduction of VLDL

IDLIDL Formed by degradation of VLDLFormed by degradation of VLDL Delivers TG’s and cholesterol to liver, degraded to LDL’sDelivers TG’s and cholesterol to liver, degraded to LDL’s B-100, EB-100, E

Lipoprotein Functions, Lipoprotein Functions, 118118 LDLLDL

Delivers Delivers hepatic cholesterol to tissueshepatic cholesterol to tissuesFormed by Formed by lipoprotein lipase modification of lipoprotein lipase modification of

VLDLVLDL in tissue in tissueTaken up by target cells via Taken up by target cells via receptor-mediated receptor-mediated

endocytosisendocytosisB-100B-100

Familial dyslipidemia IIaFamilial dyslipidemia IIa○ Increased Increased LDLLDL○ Elevated cholesterolElevated cholesterol○ Autosomal dominant, Autosomal dominant, absent/decreased LDL absent/decreased LDL

receptorreceptor

Lipoprotein Functions, Lipoprotein Functions, 118118 HDLHDL

Mediates reverse Mediates reverse cholesterol transport from cholesterol transport from tissues to liver.tissues to liver.

Repository of apoC and apoERepository of apoC and apoESecreted from liver and intestineSecreted from liver and intestine

Abetalipoproteinemia, Abetalipoproteinemia, 118118 Hereditary Hereditary inability to synthesize inability to synthesize

lipoproteinslipoproteins, because of , because of deficiency in deficiency in apoB-100 and apoB-48apoB-100 and apoB-48

Autosomal recessive, appears early in lifeAutosomal recessive, appears early in life Failure to thrive,Failure to thrive,

steatorrhea, steatorrhea,

acanthocytosis, ataxia, acanthocytosis, ataxia,

night blindnessnight blindness

chase findley, msiv. vitamins, fat soluble, 94 vitamins a, d, e, k absorption dependent on ileum...

Documents

water soluble

fat soluble

vitamin dfound

vitamin efound

vitamin kfound

vitamin kvitamins

vitamin b3 niacinfunction

vitamin b1 thiaminefunction