VI - Special Topics Flashcards
Long unbranched heteropolysaccharide chains composed of a repeating disaccharide unit
Glycosaminoglycans
Glycosaminoglycans: Amino Sugars
N-acetylglucosamine, N-acetylgalactosamine
Glycosaminoglycans: Acidic Sugars
Glucuronic Acid, Iduronic Acid
Glycosaminoglycans: (GlcNAc, GlcUA), synovial fluid, vitreous humor, loose connective tissue
Hyaluronic Acid
Glycosaminoglycans: (GalNAc, GlcUA), cartilage, bone, cornea
Chondroitin Sulfate
Glycosaminoglycans: (GlcNAc, Gal), cornea, loose connective tissue
Keratan Sulfate
Glycosaminoglycans: (GlcN, IdUA), mast cells
Heparin
Glycosaminoglycans: (GlcN, GlcUA), skin, aortic wall
Heparan Sulfate
Glycosaminoglycans: (GalNAc, IdUA), wide distribution
Dermatan Sulfate
All GAGs are covalently attached to proteins to form proteoglycans except
Hyaluronic Acid (occurs indipendently)
Covalently linked to roteins via a trihexoside serine O-glycosidic bond
Glycosaminoglycans
Structural components of the extracellular matrix, interacts with collagen, elastin, fibronectin, laminin and growth factors, bind polycations and cations as polyanions, turgor of various tissues, sieves in the ECM
Glycosaminoglycans
Glycosaminoglycans: important role in permitting cell migration during morphogenesis and wound repair, attracts water into the extracellular matrix, contributes to compressibility of cartilage
Hyaluronic Acid
Glycosaminoglycans: located at sites of calcification in endochondral bone and in cartilage
Chondroitin Sulfate
Glycosaminoglycans: play a critical role in corneal trarnsparency
Keratna Sulfate I and Dermatan Sulfate
Glycosaminoglycans: have a structural role in sclera
Dermatan Sulfate
Glycosaminoglycans: important anticoagulant, binds with factors IX and XI but its most important interaction is with plasma antithrombin III
Heparin
Glycosaminoglycans: component of plasma membranes where they may act as receptors and participate in cell adhesion and cell-cell interactions, determine charge selectiveness of renal glomerulus, component of synaptic and other vesicles
Heparan Sulfate
Synthesis of GAGs: polysaccharide chains are elongated by the sequential addition of alternating acidic and amino sugars donated by
UDP derivatives
Synthesis of GAGs: catalyzed by a family of specific
transferases
Synthesis of GAGs: Location
endoplasmic reticulum, Golgi apparatus
Degradation of GAGs: GAGs are phagocytosed, and in order to be degraded, the vesicles fuse with
lysosomes
Degradation of GAGs: lysosomal degradation of GAGs is accomplished by
acid hydrolases
Accumulation of GAGs in lysosomes due to deficiency in hydrolases
Mucoolysaccharidoses
Mucoolysaccharidoses: all are autosomal recessive except
Hunter’s Syndrome (X-linked Recessive)
Mucoolysaccharidoses: all present with mental retardation except
Morquio’s Syndrome
Mucoolysaccharidoses: Type IH, α-L-iduronidase deficiency, corneal clouding, cardiomyopathy, mental retardation
Hurler’s Syndrome
Mucoolysaccharidoses: Type II, iduronate sulfatase deficiency, no corneal clouding, cardiomyopathy, mental retardation
Hunter’s Syndrome
Mucoolysaccharidoses: Type IV, galactose-6-sulfatase deficiency, no CNS involvement, skeletal dysplasia, short stature
Morquio’s Syndrome
Proteins to which oligosaccharides are covalently attached
Glycoproteins
Short & branched carbohydrate chains, no repeating sugar units
Glycoproteins
Long & linear carbohydrate chains, repeating sugar units
Proteoglycans
Cell surface recognition, antigenicity, components of the extracellular matrix and of the mucins of the gastrointestinal and urogenital tracts
Glycoproteins
Major Classes of Glycoproteins
O-linked, N-linked, Glycosylphosphatidyinositol (GPI)-linked
O-linked Glycoproteins
Hydroxyl Groups: Serine, Threonine
N-linked Glycoprotein
Amide Group: Asparagine
Occurs through interaction of ZP3, an O-linked glycoprotein in the zona pellucida, with a surface protein on the sperm surface (galactosyl transferase)
Fertilization
Circulating leukocytes adhere to the endothelium through selectins on the latter’s cell surface
Inflammation
Deficient phosphorylation of mannose residues in N-linked glycoprotein pre-enzymes, defect in labelling of pre-enzymes so they can be correctly transported to lysosomes
I-cell Disease
Skeletal abnormalities, restricted joint movement, coarse facial features, severe psychomotor impairment
I-cell Disease
Glycoprotein of the influenza virus that allows new viruses to exit infected cells
Neuraminidase
HIV surface glycoprotein used to attached to cells
gp120
HIV surface glycoprotein used to fuse with the host cell membrane
gp41
Alteration in the glycosylation of circulating IgG molecules such that they lack galactose in their Fc regions and terminate in GlcNAc
Rheumatoid Arthritis
In Malaria, attachment of plasmodium falciparum to human cells is mediated by a _____ present on the surface of the parasite
GPI-linked Glycoprotein
Discovered by Landsteiner in 1900, membranes of the RBCs of most individuals contain one blood group substance
ABO Classification
On membranes of RBCs, the oligosaccharides that determine the specific natures of the ABO substances appear to be mostly present in
glycosphingolipids
Antigen on Type A blood
N-Acetylgalactosamine
Antigen on Type B blood
Galactose
Antigen on Type AB blood
N-Acetylgalactosamine, Galactose
Polypeptide hormones secreted by β-cells of the islets of Langerhans of the endocrine pancreas, stimulated by high blood glucose, inhibited by epinephrine
Insulin
Its receptor has tyrosine kinase activity leading to a cascade of cell-signalling responses, increased anabolism, decreased catabolism
Insulin
Mechanisms stimulated by Insulin
glucose uptake, synthesis of glycogen, protein and fat
Mechanisms inhibited by Insulin
glycogenolysis, gluconeogenesis, ketogenesis, lipolysis
Polypeptide hormone secreted by the α-cells of the islets of Langerhans of the endocrine pancreas, timulated by low blood glucose, AA and epinephrine, Inhibited by high blood glucose and insulin
Glucagon
Its receptor is a G-protein that activates adenylate cyclase to increase cAMP and protein kinase A, maintains blood glucose during periods of hypoglycemia
Glucagon
Mechanisms stimulated by Glucagon
gluconeogenesis, glycogenolysis, ketogenesis, uptake of AA
Mechanism inhibited by Glucagon
glycogenesis
Hormones that counteract insulin
glucagon, cortisol, growth hormone epinephrine
Hypoglycemia: Glucose Level
< 40 mg/dL
In ethanol intoxication, there will be less _____ & _____ hence there will be less substrates for _____ predisposing the body to _____.
OAA, pyruvate, gluconeogenesis, hypoglycemia
2-4 hour period after ingestion of a normal meal, transient increases in plasma glucose, AAs and TGs, increased insulin, decreased glucagon, anabolic
Absorptive/Fed State
Fed State: fuel for most tissues
glucose
Fed State: replenishes its glycogen stores, replaces any needed hepatic proteins, increased TG synthesis
liver
Fed State: increased TG synthesis and storage
adipose
Fed State: increased protein synthesis
muscle
Fed State: uses glucose exclusively as fuel
brain
In the abscence of food, plasma levels of glucose, AAs and TGs fall, decreased insulin, increased glucagon, catabolic
Fasting State
Fasting State: degrades glycogen, initiates gluconeogenesis, increased FA oxidation as a source of energy and to supply the acetyl CoA building blocks for ketone body synthesis
liver
Fasting State: degrades stored TG thus providing FA and glycerol to the liver
adipose
Fasting State: can also use FA as well as ketone bodies, protein is degraded to supply AA for gluconeogenesis in the liver
muscle
Fasting State: uses ketones in prolonged fasting
brain
Energy-rich molecules larger than that of the other dietary nutrients, fats, carbohydrates, protein, ethanol
Macronutrients
Nutrients needed in lesser amounts, vitamins and minerals
Micronutrients
Average daily nutrient intake level estimated to mee the requirement of 50% of healthy individuals in a particular life stage and sex
Estimated Average Requirement (EAR)
Average daily dietary intake level that is sufficient to meet the requirements of >95% of all individuals in a life stage and sex
Recommended Daily Allowance (RDA)
Arbitrarily set in the absence of scientific evidence to calculate an EAR or RDA
Adequate Intake
Highest average nutrient intake level that is likely to pose no risk of adverse health effects to almost all individuals in the general population
Tolerable Upper Intake Level
Average dietary energy intake predicted to maintain an energy balance in a healthy adult of a defined age, gender and height whose weight and level of physical activity are consistent with good health
Estimated Energy Requirement
Estimated Energy Requirement: Sedentary
30 kcal/kg/day
Estimated Energy Requirement: Moderately Active
35 kcal/kg/day
Estimated Energy Requirement: Very Active
40 kcal/kg/day
Total Caloric Requirement: In-Patients
35 kcal/kg/day
Energy Requirements: Fats
20-35%
Energy Requirements: Carbohydrates
45-65%
Energy Requirements: Proteins
10-35%
Energy Content: Fats
9 kcal/gram
Energy Content: Carbohydrates, Proteins, Ketones
4 kcal/gram
Energy Content: Alcohol
7 kcal/gram
Energy Use: at rest but not asleep, 12 hours after the last meal, depends on weight, age and sex
Resting (Basal) Metabolic Rate - 60%
Energy Use: increased metabolic rate after a meal
Diet-Induced Thermogenesis - 10%
Energy Use: most variable
Physical Activity - 30%
Food intake in excess of energy expenditure
Obesity
Food intake less that energy expenditure
Undernutrition
Protein deprivation greater the caloric reduction
Kwashiorkor
Calorie deprivation greater that protein reduction
Marasmus
Malnutrition: > 1 y.o. (after weaning from breastmilk)
Kwashiorkor
Malnutrition: stunted, edematous, low plasma protein
Kwashiorkor
Malnutrition: fatty liver, skin lesions, depigmented hair
Kwashiorkor
Malnutrition: < 1 y.o.
Marasmus
Malnutrition: stunted, extreme wasting, no edema, normal plasma protein
Marasmus
Malnutrition: anemia
Marasmus
Fat Soluble Vitamins
A, D, E, K
Vitamins: absorption is dependent in ileum bile and pancreas
Fat Soluble Vitamins
Factors affecting the absorption of fat soluble vitamins
cystic fibrosis, celiac sprue, mineral oil intake
Forms of Vitamin A
Retinol (alcohol), Retinal (aldehyde), Retinoic Acid (acid)
Promotes epithelial cell proleferation and differentiation, stored as retinyl esters, transported via retinol-binding proteins (RBP)
Vitamin A
Vitamin A: growth regulators in the epithelium
Retinoic Acid
Vitamin A: supports gametogenesis in gonads
Retinol
Vitamin A: rod and cone cells for vision
Retinal
Nyctalopia (night blindness), xerophthalmia (eye and corneal blindness), impotence, growth retardation
Vitamin A Deficiency
Earliest manifestation of vitamin A deficiency
nyctalopia
Hyperkeratosis, hepatomegaly, pseudotumor cerebri (inc. ICP), increased fractures, teratogen
Vitamin A Toxicity
Vitamin A: Precursor
β-Carotene
Forms of Vitamin D
Ergocalciferol, Cholcalciferol, Calcitriol
Vitamin D: D2, milk, plants
Ergocalciferol
Vitamin D: D3, skin, animals
Cholcalciferol
Vitamin D: 1,25-(OH)2 Cholecaldiferol
Calcitriol
Vitamin D: Precursor
7-dehydrocholesterol
Vitamin D: Storage
25-(OH) vitamin D3
Vitamin D: Active Form
1,25-(OH)2 Cholecaldiferol
Increases intestinal absorption, bone resorption and kidney rabsorption of calcium, increases PO4
Vitamin D
Vitamin D: first/25 hydroxylation
liver
Vitamin D: second/1 hydroxylation
kidney
Rickets in children, osteomalacia in adults
Vitamin D Deficiency
Highest vitamin toxicity, hyercalcemia, anorexia, nausea, thirst, stupor
Vitamin D Toxicity
Tetany seizures, Chvostek’s sign, Trosseau’s sign, long QT
Hypocalcemia
Urolithiasis, bone pain, osteoporosis, constipation, PUD, pancreatitis, depression anxiety, short QT
Hypercalcemia
Antioxidant in the lipid phase, protects membrane lipids from peroxidation, prevents oxidation of LDL (dec. atherogenesis)
Vitamin E
RBC fragility, neurologic dysfunction
Vitamin E Deficiency
Leas toxic vitamin
Vitamin E
Forms of Vitamin K
Phylloquinone (K1), Menaquinone (K2), Menadione (synthetic)
Carboxylation of glutamic acid residues in many calcium-binding proteins, coagulation factors (X, IX, VII, II), Protein C & S
Vitamin K
Vitamin produced by bacteria in the GIT
Vitamin K
Intracranial bleed in neonates due to sterile GIT and low content in breastmilk
Vitamin K Deficiency
Vitamin K Toxicity
jaundice, hemolytic anemia
Water Soluble Vitamins
Thiamine (B1), Riboflavin (B2), Niacin (B3), Pantothenic Acid (B5), Pyridoxal Phosphate (B6), Biotin (B7), Folate (B9), Cobalamin (B12), Ascorbic Acid (C)
Water soluble vitamins are non-toxic and gets washed out in the urine except
B6, B12
Active form of Vitamin B1
Thiamine Pyrophosphate (TPP)
Thiamine is used as a co-factor in
pyruvate, α-ketoglutarate and branched chain AA dehydrogenase, transketolase reactions in the HMP shunt
Vitamin B1 Deficiency
Beri-Beri, Wernicke-Korsakoff
Vitamin B1 Deficiency: polyneuritis, symmetrical muscle wasting
Dry Beri-Beri
Vitamin B1 Deficiency: heart failure, high-output cardiac failure (dilated cardiomyopathy), edema
Wet Beri-Beri
Vitamin B1 Deficiency: focal deficits, loss of memory
Wernicke-Korsakoff
Active forms of Vitamin B2
Flavin Mononucleotide (FMN), Flavin Adenine Dinucleotide (FAD)
Used as a co-factor in redox reactions as an electron carrier
Vitamin B2
Stomatitis, cheilosis, dermatitis, corneal vascularization
Vitamin B2 Deficiency
Active forms of Vitamin B3
Nicotinamide Adenine Dinucleotide ± Phosphate (NAD, NADP)
Used as a co-enzyme in redox reactions as an electron carrier, derived from tryptophan using B6
Vitamin B3
Diarrhea, dermatitis, dementia, death
Pellagra (Vitamin B3 Deficiency)
↓ tryptophan absorption
Hartnup Disease
↑ tryptophan absorption
Carcinoid Syndrome
↓ Vitamin B6
Isoniazid
Constituent of Coenzyme A, co-factor for acyl transfers, component of fatty acid synthase
Vitamin B5
Dermatitis, enteritis, alopecia, adrenal insufficiency
Vitamin B5 Deficiency
Active form of Vitamin B6
Pyridoxal Phosphate
Used as a co-enzyme in AA transamination, glycogen phosphorylase, cystathione synthase, ALA synthase, synthesis of niacin from tryptophan
Vitamin B6
Combines with pyridoxal phosphate to form an inactive derivative, peripheral neuropathy
Isoniazid
Gait problems, CNS toxicity, > 2 g/day
Vitamin B6 Toxicity
Cobalt in the center of the corrin ring
Vitamin B12
Needs IF produced by parietal cells for absorption, absorbed in the terminal ileum
Vitamin B12
Active forms of Vitamin B12: Methionine Synthesis
5-deoxyadenosylcobalamine (homocysteine + N-methyl THF → methionine + THF)
Active forms of Vitamin B12: Isomerization Reactions
Methylcobalamin (methylmalonyl mutase - methylmalonyl CoA → succinyl CoA)
Autoimmune destruction of parietal cells leading to decreased IF secretion and vitamin B12 absorption, malabsorption, absence of terminal ileummegaloblastic anemia, neuropsychiatric
Pernicious Anemia
Pernicious Anemia: Diagnostics
Schilling Test, Vitamin B12, Anti-IF
Pterin Ring + Para-AminoBenzoic Acid (PABA) + Glutamate Residues
Folic Acid
Active form of Folic Acid
Tetrahyrofolate (PABA → DHF → THF)
Used as a co-enzyme for 1-carbon transfer, methylation reactions (synthesis of purines and thymine)
Folic Acid
PABA → Dihydrofolate
Dihydropteroate Synthase
Dihydrofolate → Tetrahyrofolate
Dihydrofolate Reductase
Dihydrofolate Reductase Inhibitor
Trimethoprim
Dihydropteroate Synthase Inhibitor
Sulfamethoxazole
Megaloblastic anemia, hyersegmentation of neutrophils, macrocytic anemia, neural tube defects
Folic Acid Deficiency
Pregnant mothers must be given ___ mcg of folate daily.
400 mcg
Co-factor for carboxylation reactions
Biotin
Carboxylation Reactions
Pyruvate Carboxylase (pyruvate → oxaloacetate), Acetyl CoA carboxylase (acetyl CoA → malnyl CoA), Propionyl CoA Carboxylase (propionyl CoA → methylmalonyl CoA)
Induced by avidin in egg whites (20), dermatitis, enteritis
Biotin
Co-factor in hydroxylation of proline and lysine (collagen synthesis), dopamine β-hydroxylase (dopamine → norepinephrine), reduces Fe3+ to Fe2+ in the stomach to increase Fe absorption
Vitamin C
Loose teeth, sore gums, swollen joints, fragile vessels, anemia
Scurvy (Vitamin C Deficiency)
Amount of iron in the body
3-4 g
Amount of iron in hemoglobin
2/3 of total body iron
Storage of iron in liver, spleen, bone marrow, intestinal mucosa, pancreas, myocardium, most abundant form when tissue stores are low
Ferritin
Partially denatured derivative of ferritin, predominates when iron stores are high
Hemosiderin
Iron transport protein in plasma
Transferrin
Most common micronutrient deficiency
Iron Deficiency Anemia
↓ total plasma iron, ↓ transferrin saturation, ↓ serum ferritin, ↑ total iron binding capacity
Iron Deficiency Anemia
Iron overload syndrome with progressive hemosiderosis and resulting organ damage,, may lead to liver cirrhosis, liver cancer, DM, cardiomyopathy, hyperpigmentation, endocrine disorders, joint pain, common in old men
Hemochromatosis
↑ total plasma iron, ↑ transferrin saturation, ↑ serum ferritin, ↑ total iron binding capacity
Hemochromatosis
Hemochromatosis: Treatment
repeated phlebotomy
Most abundant trace mineral in the body after iron, constituent of metalloenzymes
Zinc
Amount of zinc in the body
1.5-2.5 g
Zinc Metalloenzymes
Carbonic Anhydrase, Cytoplasmic Superoxide Dismutase, Alcohol Dehydrogenase, Carboxypeptidases A & B, DNA & RNA Polymerases
Serves a structural role by stabilizing small loops in the polypeptide
Zinc Finger Proteins
Dermatitis, poor wound healing, hair loss, neuropsychiatric impairments, decreased taste acuity, poor growth testicular atrophy
Zinc Deficiency
Rare recessive disease with dermatitis, diarrhea and alopecia due to impaired zinc absorption
Acrodermatitis Enteropathica
Amount of copper in the body
80-110 mg
Major co-factor in enzymes that use either molecular oxygen or an oxygen derivative as one of their substrates
Copper
Enzymesthat use copper as a co-factor
Cytochrome Oxidase, Dopamine β-hydroxylase, Monoamine Oxidase, Tyrosinase, Δ9 Desaturase, Lysyl Oxidase, Cytoplasmic Superoxide Dismutase
Majority of copper is transported in the serum bound to _____ with the rest loosely bound to albumin or complexed with histidine
ceruloplasmin (60%)
Microcytic, hypochromic anemia, leukopenia, hemorrhagic vascular changes, bone demineralization, hypercholesterolemia, neurological problems, TPN
Copper Deficiency
X-linked recessive disorder caused by the deficiency of an ATP-dependent membrane transporter for copper, impaired transfer of copper from intestinal mucosal cells to the blood, abnormal intracellular transport
Menkes Syndrome
Growth retardation, mental deficiency, seizures, arterial aneurysms, bone demineralization, brittle hair
Menkes Syndrome
Hepatolenticular degeneration, intestinal absorption of copper is intact but biliary excretion is blocked, copper accumulation in liver and brain, liver damage, neurological deterioration, Kayser-Fleischer Rings
Wilson Disease
Wilson Disease: Treatment
D-Penicillamine (forms a soluble, excretable copper complex)
Stimulates the activity of many enzymes, can be replaced by Magnesium in most cases
Manganese
Manganese excess causing psychosis and parkinsonism
Manganese Madness
Occurs in a few oxidase enzymes like xanthine oxidase
Molybdenum
In the form of selenocysteine, occurs in about 20 human proteins including glutathione peroxidase
Selenium
Low selenium content causing cardiomyopathy, endemic in parts of China
Keshan Disease
Halogen needed for the synthesis of thyroid hormones
Iodine
Can be incorporated in the inorganic substance of bones and teeth
Fluorine
Medical compounds that are foreign to the body
Xenobiotics
Major organ involved in xenobiotics
liver
Phases of Xenobiotic Metabolism
Phase I (hydroxylation), Phase II (conjugation)
Phase I Reaction Enzymes
Monooxygenases of Cytochrome P450s
Catalyzes phase I reactions, located in the endoplasmic reticulum, enriched in the liver, inducible
Cytochrome P450
Conversion of polar and water-soluble metabolites, methylation, conjugation with glucuronic acid, sulfate, acetate, glutathione or AAs
Phase II Metabolism
Phase II Reaction Enzymes
Glucuronosyltransferases, Sulfotransferases, Glutathione S-transferases
