Metabolism

Question 1

fed state

Answer 1

AKA absorptive state

begins within 2-4 hours of eating a meal and during this period, the body is absorbing and utilizing the glucose provided to our cells via our dietary intake

Question 2

fasting state

Answer 2

AKA post-absorptive or post-prandial state

beings 2-4 hours after caloric intake and during this period, blood glucose levels decrease beginning around 1 hour after a meal and eventually reach a basal metabolic state at ~12 hours

blood glucose levels are maintained by glycogen breakdown first and gluconeogenesis second

Question 3

starved state

Answer 3

begins when the body is deprived of dietary intake for 3 or more days, and during this stage, blood glucose levels are maintained primarily through gluconeogenesis

d/t protein sparing and changes in fuel use patterns (reserving the maorityj of energy sources for brain and essential functions), we are able to endure prolonged stretches of time w/o dietary intake

Question 4

what tissue can only use glucose

Answer 4

RBCs via anaerobic respiration

Question 5

what energy source does the brain use during the fed state

Answer 5

exclusively glucose

Question 6

major fuels from diet

Answer 6

carbohydrates, proteins, and fats

also alcohol

Question 7

GLUT-2

Answer 7

the primary glucose transporter for hepatocytes, and is found in liver, kidney, and beta-cells

allows bidirectional transport, and has a low affinity for ALL 3 monosaccharides (i.e. only takes up in high concentration)

Question 8

GLUT-4

Answer 8

the primary glucose transporter in adipose tissue, and skeletal and cardiac muscle

insulin sensitive

Question 9

glucokinase

Answer 9

phosphorylates glucose in the liver to prevent the glucose molecule from leaving the cell

Question 10

hexokinase

Answer 10

phosphorylates glucose in tissues other than the liver to prevent the glucose molecule from leaving the cell

Question 11

GLUT-1

Answer 11

glucose transporter that has a low expression on most cell types, but has a high expression in erythrocytes and endothelial cells of barrier tissues (e.g. the blood-brain barrier) d/t high affinity

Question 12

glycolysis

Answer 12

converts glucose to Acetyl CoA in the cytosol

Question 13

most tissue types are able to obtain energy from carbohydrates via what mechanism

Answer 13

aerobic respiration

Question 14

nicotinamide adenine dinucleotide

Answer 14

NAD; most important coenzyme (electron carrier) for catabolic reactions d/t its capability to accept (or donate) electrons from intermediates of metabolism

as its name implies, it is composed of 2 nucleotides linked by their phosphate groups, and can be found in reduced (NADH) or oxidized (NAD+) states

Question 15

in the fed state, excess carbohydrates can be stored as what

Answer 15

glycogen or fat

Question 16

which organs/tissues have their glycogen levels replenished first, followed by what

Answer 16

liver and muscle

as glycogen levels rise, more carbohydrates are converted into fat

Question 17

what is the purpose of phosphorylation of glucose once it is transported into the cell

Answer 17

to prevent movement of glucose out of the cell

Question 18

what is unique about skeletal muscle regarding glycogen synthesis

Answer 18

skeletal muscle lacks G6 phosphatase

Question 19

what type of bonds are formed in glycogen synthesis

Answer 19

alpha(1->6) bond

Question 20

why is glycogen branched

Answer 20

increased solubility and increased efficiency for rapid mobilization

Question 21

lipoprotein complexes

Answer 21

how triglycerides travel through the bloodstream

Question 22

VLDL

Answer 22

used specifically to transport triglycerides from the liver to tissue sites (like adipose tissue)

Question 23

Maple Syrup Urine Disease

Answer 23

an example of IEM AA breakdown is the site of many of these metabolic disorders

Question 24

ways amino acids obtained from the metabolism of protein in our diet can be used

Answer 24

as a source of energy by feeding into the TCA cycle

can be used in the synthesis of new proteins

can be used to generate compounds derived from amino acids including other amino acids

Question 25

what is the primary source of glucose during the fasting state

Answer 25

glycogen breakdown in the liver

skeletal muscle glycogen can also be accessed for use in muscle during this state but not to maintain blood glucose levels

Question 26

Glycogen Storage Diseases

Answer 26

a variety of genetic disorders that arise from mutations in genes involved in glycogen breakdown (or synthesis)

Question 27

gluconeogenesis

Answer 27

can synthesize glucose from triglyceride and protein breakdown [can think of it as glycolysis in reverse]

occurs primarily in the liver

the rate of glucose formation by gluconeogenesis increases as glycogen levels decrease (inverse relationship)

Question 28

Cori cycle

Answer 28

used to describe the process by which lactate is used as a substrate to produce glucose via gluconeogenesis

particularly important for dealing with the large amount of lactate generated by RBCs or muscles undergoing anaerobic respiration

Question 29

β-oxidation

Answer 29

the process by which fatty acids are oxidized to acetyl-CoA which can then feed into the TCA cycle and subsequently electron transport

Question 30

lipases present in adipose tissue

Answer 30

responsible for breaking down triglycerides into one glycerol molecule and three fatty acid molecules

the glycerol molecule is used specifically in gluconeogenesis

Question 31

the secondary site of stored energy

Answer 31

adipose tissue

Question 32

Hormone Sensitive Lipase

Answer 32

activated by glucagon to cleave TAGs

Question 33

ketone bodies

Answer 33

can be used as an alternative source of energy by tissues other than the liver during fasting and most importantly during starvation

in the liver, produced by most of the acetyl-CoA generated by β-oxidation

Question 34

the alternative source of energy of tissues other than the liver during fasting and especially during starvation

Answer 34

ketone bodies

Question 35

proteins in the fasting state

Answer 35

the breakdown of proteins during fasting generates amino acids which can be used to generate glucose via gluconeogenesis

the nitrogen released from protein degradation produces a large amount of ammonia (toxic) which is converted by the liver to urea (urea cycle) and excreted in our urine by the kidney

Question 36

urea cycle

Answer 36

conversion of ammonia, which is toxic, into urea and then the urea is excreted by the kidney through urine

Question 37

metabolic changes that occur as bodies transition from the fasting to the starved state

Answer 37

glycogen levels are being depleted, so glycerol from fat breakdown is being used to form glucose (gluconeogenesis) and this glucose is used by RBCs & to maintain blood glucose levels

protein catabolism is markedly diminished to prevent muscle wasting, but this compromises cell function so only vital functions are preserved; liver decreases urea production (b/c less ammonia is generated)

muscle utilizes fatty acids and stops using ketone bodies (KBs)

the brain begins to use KBs and decrease use of glucose

Question 38

the length of time in which we can undergo starvation is dependent on what

Answer 38

the amount of adipose tissue present to meet energy demands

the amount of protein present to meet cell/organ regeneration requirements

vitamins and minerals present to function as cofactors

electrolyte levels

Question 39

vitamin B9

Answer 39

describes many forms of naturally occurring folate, but folic acid is the synthetic form of folate that is used in supplements and in fortification of foods

plays a key role in one-carbon metabolism, and it is essential for the biosynthesis of several compound

Question 40

folic acid deficiency

Answer 40

probably the most common vitamin deficiency in the US, particularly among pregnant women and individuals with alcoholism

Question 41

folic acid function

Answer 41

Tetrahydrofolate (THF), the reduced, coenzyme form of folate, receives one-carbon fragments from donors such as Ser, Gly, and His and transfers them to intermediates in the synthesis of amino acids, purine nucleotides, and thymidine monophosphate (TMP), a pyrimidine nucleotide incorporated into DNA

Question 42

nutritional anemias

Answer 42

anemia caused by inadequate intake of one or more essential nutrients; can be classified according to the size of the red blood cells (RBCs), or mean corpuscular volume (MCV), observed in the blood

Question 43

anemia

Answer 43

a condition in which the blood has a lower than normal concentration of hemoglobin, which results in a reduced ability to transport oxygen

Question 44

Microcytic anemia

Answer 44

MCV is below normal, and is caused by a lack of iron

most common form of nutritional anemia

Question 45

macrocytic anemia

Answer 45

MCV is above normal and results from a deficiency in folic acid or vitamin B12

commonly called megaloblastic because a deficiency of either vitamin [or both] causes the accumulation of large, immature RBC precursors, known as megaloblasts, in the bone marrow and the blood

Question 46

what can cause inadequate serum levels of folate

Answer 46

increased demand of folate (e.g. pregnancy and lactation)

poor absorption caused by pathology of the small intestine

alcoholism

treatment with drugs (e.g., methotrexate) that are dihydrofolate reductase inhibitors

Question 47

a primary result of folic acid deficiency

Answer 47

megaloblastic anemia which is caused by diminished synthesis of purine nucleotides and TMP (thymidine monophosphate)

this leads to an inability of cells (including RBC precursors) to make DNA and, therefore, an inability to divide

Question 48

most common neural tube defects (NTDs)

Answer 48

spina bifida and anencephaly (affect ∼3,000 pregnancies in the United States annually)

can be reduced with folic acid supplementation before conception and during the first trimester

Question 49

folic acid dose for women of childbearing age

Answer 49

0.4 mg/day (400 μg/day) of folic acid to reduce the risk of having a pregnancy affected by NTD and ten times that amount if a previous pregnancy was affected

Question 50

vitamin B12

Answer 50

also called cobalamin

required in humans for two essential enzymatic reactions:

the remethylation of homocysteine (Hcy) to methionine

the isomerization of methylmalonyl coenzyme A (CoA), which is produced during the degradation of some amino acids (Ile, Val, Thr, and Met) and fatty acids (FA) with odd numbers of carbon atoms

Question 51

cobalamin deficiency

Answer 51

causes unusual (branched) fatty acids (FA) to accumulate and to become incorporated into cell membranes, including those of the (CNS); this may account for some of the neurologic manifestations of vitamin B12 deficiency

Question 52

cobalamin structure

Answer 52

contains a corrin ring system, in which two of the pyrrole rings are linked directly rather than through a methene bridge (as in the porphyrin ring of heme)

cobalt is held in the center of the corrin ring by four coordination bonds with the nitrogens of the pyrrole groups

the remaining coordination bonds of the cobalt are with the nitrogen of 5,6-dimethylbenzimidazole and with cyanide in commercial preparations of the vitamin in the form of cyanocobalamin

Question 53

the physiologic coenzyme forms of cobalamin

Answer 53

5′-deoxyadenosylcobalamin (cyanide is replaced with 5′-deoxyadenosin)

methylcobalamin (cyanide is replaced with a methyl group)

Question 54

cobalamin distribution

Answer 54

synthesized only by microorganisms, and is not present in plants

animals obtain the vitamin preformed from their intestinal microbiota or by eating foods derived from other animals

cobalamin is present in appreciable amounts in liver, red meat, fish, eggs, dairy products, and fortified cereals

Question 55

folate trap hypothesis

Answer 55

results from cobalamin deficiency in tissues with rapidly dividing cells, as such tissues need both the N5,N10-methylene and N10-formyl forms of THF for the synthesis of nucleotides required for DNA replication

in vitamin B12 deficiency, the utilization of the N5-methyl form of THF in the B12-dependent methylation of Hcy to Met is impaired

because the methylated form cannot be converted directly to other forms of THF, folate is trapped in the N5-methyl form, which accumulates and the levels of the other forms decrease

thus, cobalamin deficiency leads to a deficiency of the THF forms needed in purine and TMP synthesis, resulting in the symptoms of megaloblastic anemia.

Question 56

in which cells are the effects of cobalamin deficiency most pronounced

Answer 56

in rapidly dividing cells, such as the erythropoietic tissue of bone marrow and the mucosal cells of the intestine.

Question 57

clinical indications for cobalamin

Answer 57

significant amounts (2 to 5 mg) of vitamin B12 are stored in the body, and so it may take several years for the clinical symptoms of B12 deficiency to develop as a result of decreased intake of the vitamin

can perform Schilling test to assess absorption

can be determined by the level of methylmalonic acid in blood, which is elevated in individuals with low intake or decreased absorption of the vitamin

Question 58

the Schilling test

Answer 58

evaluates B12 absorption

Question 59

pernicious anemia

Answer 59

caused by a severe malabsorption of B12, which is most commonly a result of an autoimmune destruction of the gastric parietal cells that are responsible for the synthesis of IF (lack of IF prevents B12 absorption)

anemic d/t folate recycling being impared and neuropsychiatric symptoms as the disease develop (the CNS effects are irreversible)

Question 60

pernicious anemia treatment

Answer 60

requires lifelong treatment with either high-dose oral B12 or intramuscular injection of cyanocobalamin

Question 61

cobalamin absorbtion pathway

Answer 61

B12 is released from food in the acidic environment of the stomach, and free B12 then binds a glycoprotein (R-protein or haptocorrin) before the complex moves into the intestine

B12 is released from the R-protein by pancreatic enzymes and binds another glycoprotein, intrinsic factor (IF)

the cobalamin–IF complex travels through the intestine and binds to a receptor (cubilin) on the surface of mucosal cells in the ileum

then cobalamin is transported into the mucosal cell and, subsequently, into the general circulation, where it is carried by its binding protein (transcobalamin)

B12 is taken up and stored in the liver, primarily, and it is released into bile and efficiently reabsorbed in the ileum

Question 62

transcobalamin

Answer 62

binding protein for B12

Question 63

vitamin A

Answer 63

a fat-soluble vitamin that comes primarily from animal sources as retinol (preformed vitamin A), a retinoid

Question 64

retinoids

Answer 64

a family of structurally related molecules that are essential for vision, reproduction, growth, and maintenance of epithelial tissues

also play a role in immune function

Question 65

retinoic acid

Answer 65

derived from the oxidation of retinol, it mediates most of the actions of the retinoids, except for vision, which depends on retinal, the aldehyde derivative of retinol

Question 66

retinal

Answer 66

the aldehyde derivative of retinol which mediates the actions of the retinoids for vision

Question 67

retinoids structure

Answer 67

include the natural forms of vitamin A, retinol and its metabolites, and synthetic forms (drugs)

Question 68

retinol overview and structure

Answer 68

primary alcohol containing a β-ionone ring with an unsaturated side chain

found in animal tissues as a retinyl ester with long-chain FA

the storage form of vitamin A

Question 69

retinal structure

Answer 69

the aldehyde derived from the oxidation of retinol

retinal and retinol can readily be interconverted

Question 70

retinoic acid structure

Answer 70

the acid which is derived from the oxidation of retinal

retinoic acid cannot be reduced in the body and, therefore, cannot give rise to either retinal or retinol

Question 71

β-Carotene overview structure

Answer 71

plant foods contain β-carotene (provitamin A), which can be oxidatively and symmetrically cleaved in the intestine to yield two molecules of retinal

in humans, the conversion is inefficient, and the vitamin A activity of β-carotene is only about 1/12 that of retinol.

Question 72

vitamin A absorption

Answer 72

retinyl esters from the diet are hydrolyzed in the intestinal mucosa, releasing retinol and FFA

retinol derived from esters and from the reduction of retinal from β-carotene cleavage is reesterified to long-chain FA within the enterocytes and secreted as a component of chylomicrons into the lymphatic system

retinyl esters contained in chylomicron remnants are taken up by, and stored in, the liver

Question 73

fat-soluble vitamins carrier

Answer 73

all fat-soluble vitamins are carried in chylomicrons

Question 74

vitamin A release from liver

Answer 74

retinol is released from the liver and transported through the blood to extrahepatic tissues by retinol-binding protein complexed with transthyretin

the ternary complex binds to a transport protein on the surface of the cells of peripheral tissues, permitting retinol to enter

an intracellular retinol-binding protein carries retinol to sites in the nucleus where the vitamin regulates transcription in a manner analogous to that of steroid hormones

Question 75

retinoic acid mechanism of action

Answer 75

retinol is oxidized to retinoic acid, which binds with high affinity to retinoic acid receptors (RARs) present in the nucleus of target tissues to form an activated retinoic acid–RAR complex

Question 76

retinoic acid receptors (RARs)

Answer 76

specific receptors found in the nucleus of target cells which bind with high affinity to retinoic acid

Question 77

activated retinoic acid–RAR complex

Answer 77

binds to response elements on DNA and recruits activators or repressors to regulate retinoid-specific RNA synthesis, resulting in control of the production of specific proteins that mediate several physiologic functions

Question 78

vitamin A functions

Answer 78

visual cycle - VitA is a component of the visual pigments of rod and cone cells

epithelial cell maintenance - Vitamin A is essential for normal differentiation of epithelial tissues and mucus secretion

reproduction - retinol and retinal support spermatogenesis in males and preventing fetal resorption in females

Question 79

rhodopsin

Answer 79

a G protein-coupled receptor and the visual pigment of the rod cells in the retina

consists of 11-cis retinal bound to the protein opsin

[rhod -> rod; 11 retaining cisterna are bound to the opsin]

Question 80

when rhodopsin is exposed to light

Answer 80

a series of photochemical isomerizations occurs, which results in the bleaching of rhodopsin and release of all-trans retinal and opsin

this activates the G protein transducin, triggering a nerve impulse that is transmitted by the optic nerve to the brain

Question 81

regeneration of rhodopsin

Answer 81

requires isomerization of all-trans retinal back to 11-cis retinal

(all-trans retinal is reduced to all-trans retinol, esterified, and isomerized to 11-cis retinol that is oxidized to 11-cis retinal)

the 11-cis retinal combines with opsin to form rhodopsin, and thus completes the cycle

Question 82

vitamin A distribution

Answer 82

liver, kidney, cream, butter, and egg yolk are good sources of preformed vitamin A

yellow, orange, and dark-green vegetables and fruits are good sources of the carotenes (provitamin A)

Question 83

RDA for vitamin A

Answer 83

for adults, RDA is 900 retinol activity equivalents (RAE) for males and 700 RAE for females

(in comparison, 1 RAE = 1 μg of retinol, 12 μg of β-carotene, or 24 μg of other carotenoids)

Question 84

vitamin A deficiencies in vision

Answer 84

early sign -> night blindness (nyctalopia) b/c the visual threshold is increased, making it more difficult to see in dim light

prolonged deficiency -> an irreversible loss in the number of visual cells

severe deficiency -> xerophthalmia, a pathologic dryness of the conjunctiva and cornea; if untreated, xerophthalmia results in corneal ulceration and, ultimately, blindness b/c of the formation of opaque scar tissue

Question 85

xerophthalmia

Answer 85

a pathologic dryness of the conjunctiva and cornea, caused, in part, by increased keratin synthesis

if untreated, xerophthalmia results in corneal ulceration and, ultimately, blindness

Question 86

night blindness

Answer 86

nyctalopia; can be caused by a vitamin A deficiency

Question 87

tretinoin

Answer 87

all-trans retinoic acid which is used to treat mild cases of acne and skin aging topically

Question 88

isotretinoin

Answer 88

13-cis retinoic acid which is administered orally to treat severe cystic acne

Question 89

retinoid toxicity threshold

Answer 89

amounts exceeding 7.5 mg/day of retinol should be avoided as excessive intake of vitamin A (but not carotene) produces a toxic syndrome called hypervitaminosis A

Question 90

early signs of chronic hypervitaminosis A

Answer 90

the skin becomes dry and pruritic (because of decreased keratin synthesis)

the liver becomes enlarged and can become cirrhotic

the CNS sees a rise in intracranial pressure may mimic the symptoms of a brain tumor

Question 91

hypervitaminosis A in pregnancy

Answer 91

excessive quantities of vitamin A has potential for teratogenesis (causing congenital malformations in the developing fetus)

Question 92

vitamin D

Answer 92

a group of sterols that have a hormone-like function

the active molecule, 1,25-dihydroxycholecalciferol ([1,25-diOH-D3], or calcitriol), binds to intracellular receptor proteins and the 1,25-diOH-D3–receptor complex interacts with response elements in the nuclear DNA of target cells to either stimulates or represses gene transcription

Question 93

most prominent actions of calcitriol

Answer 93

to regulate the serum levels of calcium and phosphorus

Question 94

calcitriol

Answer 94

1,25-dihydroxycholecalciferol ([1,25-diOH-D3]

the active molecule of vitamin D

overall function is to maintain adequate serum levels of Ca2+

Question 95

7-Dehydrocholesterol

Answer 95

an intermediate in cholesterol synthesis which is converted to cholecalciferol in the dermis and epidermis of humans exposed to sunlight

Question 96

cholecalciferol

Answer 96

what 7-Dehydrocholesterol is converted to in the dermis and epidermis of humans exposed to sunlight

transported to the liver bound to vitamin D–binding protein

Question 97

ergocalciferol

Answer 97

vitamin D2, found in plants

source of preformed vitamin D activity

Question 98

cholecalciferol

Answer 98

vitamin D3, found in animals

source of preformed vitamin D activity

Question 99

Vitamin D2 and Vitamin D3 chemical difference

Answer 99

differ only in the presence of an additional double-bond and methyl group in the plant sterol

Question 100

1,25-Dihydroxycholecalciferol formation overview

Answer 100

vitamin D2 and D3 are converted in vivo to calcitriol by two sequential hydroxylation reactions performed by cytochrome P450 proteins

Question 101

the first hydroxylation during calcitriol formation

Answer 101

occurs at the 25 position and is catalyzed by a specific 25-hydroxylase in the liver

the product of the reaction, 25-hydroxycholecalciferol ([25-OH-D3], calcidiol), is the predominant form of vitamin D in the serum and the major storage form

Question 102

calcidiol

Answer 102

25-hydroxycholecalciferol (25-OH-D3)

the product of the first hydroxylation of vitamins D2 and D3 at the 25 position by 25-hydroxylase in the liver

the predominant form of vitamin D in the serum and the major storage form

Question 103

25-hydroxylase

Answer 103

catalyzes the first hydroxylation of vitamins D2 and D3 at the 25 position to produce 25-hydroxycholecalciferol ([25-OH-D3], calcidiol)

occurs in the liver

Question 104

the second hydroxylation during calcitriol formation

Answer 104

25-OH-D3 (calcidiol) is further hydroxylated at the 1 position by 25-hydroxycholecalciferol 1-hydroxylase (a cytochrome P450 protein) found primarily in the kidney, resulting in the formation of 1,25-diOH-D3 (calcitriol)

Question 105

25-hydroxycholecalciferol 1-hydroxylase

Answer 105

a cytochrome P450 protein found primarily in the kidney which hydroxylates 25-OH-D3 (calcidiol) into 1,25-diOH-D3 (calcitriol)

its activity is increased directly by low serum PO43− or indirectly by low serum Ca2+, which triggers the secretion of parathyroid hormone (PTH) from the chief cells of the parathyroid gland and PTH then upregulates the 1-hydroxylase

Question 106

calcitriol formation regulation

Answer 106

tightly regulated by the level of serum phosphate (PO43−) and calcium ions (Ca2+)

25-Hydroxycholecalciferol 1-hydroxylase activity is increased directly by low serum PO43− or indirectly by low serum Ca2+, which triggers the secretion of parathyroid hormone (PTH) from the chief cells of the parathyroid gland and PTH upregulates the 1-hydroxylase

thus, hypocalcemia caused by insufficient dietary Ca2+ results in elevated levels of serum 1,25-diOH-D3

calcitriol inhibits expression of PTH and the activity of 1-hydroxylase, negative feedback loops

Question 107

how calcitriol maintains adequate serum levels of Ca2+

Answer 107

increasing uptake of Ca2+ by the intestine

minimizing loss of Ca2+ by the kidney by increasing reabsorption

stimulating resorption (demineralization) of bone when blood Ca2+ is low

Question 108

calcitriol path in the intestine

Answer 108

(the mechanism of action of 1,25-diOH-D3 is typical of steroid hormones)

1) calcitriol enters the intestinal cell and binds to a cytosolic receptor
2) the 1,25-diOH-D3–receptor complex then moves to the nucleus where it selectively interacts with response elements on the DNA
3) increased expression of the calcium-binding protein calbindin results in increased Ca2+ uptake

Question 109

calcitriol effect on bones

Answer 109

b/c bone is composed of collagen and crystals of Ca5(PO4)3OH (hydroxylapatite), when blood Ca2+ is low, 1,25-diOH-D3 stimulates bone resorption by a process that is enhanced by PTH -> increase in Ca2+

Question 110

vitamin d distribution

Answer 110

occurs naturally in fatty fish, liver, and egg yolk. Milk, unless it is artificially fortified, is not a good source

Question 111

vitamin D RDA

Answer 111

15 μg/day for individuals of ages 1 to 70 years and 20 μg/day if over age 70 years

experts disagree, however, on the optimal level of vitamin D needed to maintain health

breast milk is a poor source of vitamin D, so supplementation is recommended for breastfed babies

Question 112

nutritional rickets

Answer 112

caused by a vitamin D deficiency which leads to the net demineralization of bone, resulting in rickets in children and osteomalacia in adults

rickets: characterized by the continued formation of the collagen matrix of bone, but incomplete mineralization results in soft, pliable bones
osteomalacia: demineralization of pre-existing bones increases their susceptibility to fracture

Question 113

renal osteodystrophy

Answer 113

CKD causes decreased ability to form active vitamin D as well as increased retention of PO43−, resulting in hypocalcemia adn hyperphosphatemia

the low blood Ca2+ causes a rise in PTH and associated bone demineralization with the release of Ca2+ and PO43−

supplementation with vitamin D is an effective therapy, with PO43− reduction therapy to prevent further bone loss and precipitation of calcium phosphate crystals

Question 114

hypoparathyroidism

Answer 114

lack of PTH causes hypocalcemia and hyperphosphatemia. (PTH increases phosphate excretion)

patients may be treated with vitamin D and calcium supplementation.

Question 115

vitamin D toxicity

Answer 115

high doses (100,000 IU for weeks or months) can cause loss of appetite, nausea, thirst, and weakness

enhanced Ca2+ absorption and bone resorption result in hypercalcemia, which can lead to the deposition of calcium salts in soft tissue (metastatic calcification

Question 116

vitamin K1

Answer 116

also known as phylloquinone, an active form of vitamin K which exists in plants

Question 117

the principal role of vitamin K

Answer 117

the posttranslational modification of a number of proteins (most of which are involved with blood clotting), in which it serves as a coenzyme in the carboxylation of certain glutamic acid residues in these proteins

Question 118

vitamin K2

Answer 118

also known as menaquinone, an active form of vitamin K, which exists in intestinal bacteria

Question 119

menadione

Answer 119

a synthetic form of vitamin K which is able to be converted to K2 (menaquinone)

Question 120

γ-Carboxyglutamate (Gla) function

Answer 120

required for functional versions of the coagulation factors prothrombin, FVII, FIX and FX

Question 121

γ-Carboxyglutamate (Gla) formation

Answer 121

created via vitamin K-dependent carboxylation of several glutamic acid residues during the posttranslational modification of coagulation factors prothrombin, FVII, FIX, and FX

the carboxylation reaction requires γ-glutamyl carboxylase, O2, CO2, and the hydroquinone form of vitamin K

Question 122

γ-glutamyl carboxylase

Answer 122

required for the carboxylation reaction of glutamic acid residues to γ-carboxyglutamate (Gla) residues within the enzyme factors prothrombin, FVII, FIX, and FX

works with O2, CO2, and the hydroquinone form of vitamin K during this reaction

Question 123

warfarin

Answer 123

a synthetic analog of vitamin K that inhibits vitamin K epoxide reductase (VKOR), the enzyme required to regenerate the functional hydroquinone form of vitamin K

this inhibits the formation of γ-carboxyglutamate (Gla) residues, which inhibits clotting (d/t its presence within several coagulation factors)

Question 124

vitamin K epoxide reductase (VKOR)

Answer 124

the enzyme required to regenerate the functional hydroquinone form of vitamin K

Question 125

γ-carboxyglutamate (Gla) residues role within coagulation enzymes

Answer 125

γ-carboxyglutamate (Gla) residues are good chelators of positively charged calcium ions, because of their two adjacent, negatively charged carboxylate groups

E.g. the prothrombin–calcium complex is able to bind to negatively charged membrane phospholipids on the surface of damaged endothelium and platelets

Question 126

vitamin K distribution

Answer 126

found in cabbage, kale, spinach, egg yolk, and liver

there is also synthesis of the vitamin by the gut microbiota.

Question 127

vitamin K RDA

Answer 127

the adequate intake for vitamin K is 120 μg/day for adult males and 90 μg for adult females

Question 128

vitamin K deficiency generally

Answer 128

unusual because adequate amounts are generally obtained from the diet and produced by intestinal bacteria

if decreased, can lead to hypoprothrombinemia which may require supplementation with vitamin K to correct the bleeding tendency

can affect bone health

Question 129

vitamin K deficiency in newborn

Answer 129

newborns initially lack the bacteria that synthesize vitamin K and human milk provides only about one-fifth of the daily requirement for vitamin K

thus, it is recommended that all newborns receive a single intramuscular dose of vitamin K as prophylaxis against hemorrhagic disease of the newborn.

Question 130

vitamin K toxicity

Answer 130

prolonged administration of large doses of menadione can produce hemolytic anemia and jaundice in the infant, because of toxic effects on the RBC membrane

therefore, it is no longer used to treat vitamin K deficiency

no UL for the natural form has been set

Question 131

the E vitamins composition

Answer 131

consist of eight naturally occurring tocopherols, of which α-tocopherol is the most active

Question 132

vitamin E function

Answer 132

functions as an antioxidant in the prevention of nonenzymic oxidations (e.g., oxidation of LDL and peroxidation of polyunsaturated FA by O2 and free radicals)

Question 133

vitamin E distribution

Answer 133

vegetable oils are rich sources of vitamin E, whereas liver and eggs contain moderate amounts

Question 134

RDA for α-tocopherol

Answer 134

15 mg/day for adults

the vitamin E requirement increases as the intake of polyunsaturated FA increases to limit FA peroxidation

Question 135

vitamin E deficiency in newborns

Answer 135

hemolysis and retinopathy associated with vitamin E deficiency

while newborns have low reserves of vitamin E, breast milk (and formulas) contain the vitamin, but very–low-birth-weight infants may be given supplements to prevent the sxa above

Question 136

vitamin E deficiency in adults

Answer 136

usually associated with defective lipid absorption or transport

Question 137

abetalipoproteinemia

Answer 137

caused by a defect in the formation of chylomicrons [and VLDL], results in vitamin E deficiency

Question 138

clinical indications for vitamin E

Answer 138

Vitamin E is not recommended for the prevention of chronic diseases, such as CVD or cancer

clinical trials using vitamin E supplementation have been uniformly disappointing

Question 139

vitamin E toxicity

Answer 139

the least toxic of the fat-soluble vitamins

no toxicity has been observed at doses of 300 mg/day

Question 140

marasmus

Question 141

kwashiorkor

Question 142

mixed marasmus-kwashiorkor

Answer 142

these children often have concurrent wasting and edema in addition to stunting. These children exhibit features of dermatitis, neurologic abnormalities, and fatty liver.