Metabolism Flashcards
1
Q
fed state
A
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
2
Q
fasting state
A
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
3
Q
starved state
A
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
4
Q
what tissue can only use glucose
A
RBCs via anaerobic respiration
5
Q
what energy source does the brain use during the fed state
A
exclusively glucose
6
Q
major fuels from diet
A
carbohydrates, proteins, and fats
also alcohol
7
Q
GLUT-2
A
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)
8
Q
GLUT-4
A
the primary glucose transporter in adipose tissue, and skeletal and cardiac muscle
insulin sensitive
9
Q
glucokinase
A
phosphorylates glucose in the liver to prevent the glucose molecule from leaving the cell
10
Q
hexokinase
A
phosphorylates glucose in tissues other than the liver to prevent the glucose molecule from leaving the cell
11
Q
GLUT-1
A
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
12
Q
glycolysis
A
converts glucose to Acetyl CoA in the cytosol
13
Q
most tissue types are able to obtain energy from carbohydrates via what mechanism
A
aerobic respiration
14
Q
nicotinamide adenine dinucleotide
A
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
15
Q
in the fed state, excess carbohydrates can be stored as what
A
glycogen or fat
16
Q
which organs/tissues have their glycogen levels replenished first, followed by what
A
liver and muscle
as glycogen levels rise, more carbohydrates are converted into fat
17
Q
what is the purpose of phosphorylation of glucose once it is transported into the cell
A
to prevent movement of glucose out of the cell
18
Q
what is unique about skeletal muscle regarding glycogen synthesis
A
skeletal muscle lacks G6 phosphatase
19
Q
what type of bonds are formed in glycogen synthesis
A
alpha(1->6) bond
20
Q
why is glycogen branched
A
increased solubility and increased efficiency for rapid mobilization
21
Q
lipoprotein complexes
A
how triglycerides travel through the bloodstream
22
Q
VLDL
A
used specifically to transport triglycerides from the liver to tissue sites (like adipose tissue)
23
Q
Maple Syrup Urine Disease
A
an example of IEM AA breakdown is the site of many of these metabolic disorders
24
Q
ways amino acids obtained from the metabolism of protein in our diet can be used
A
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
25
what is the primary source of glucose during the fasting state
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
26
Glycogen Storage Diseases
a variety of genetic disorders that arise from mutations in genes involved in glycogen breakdown (or synthesis)
27
gluconeogenesis
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)
28
Cori cycle
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
29
β-oxidation
the process by which fatty acids are oxidized to acetyl-CoA which can then feed into the TCA cycle and subsequently electron transport
30
lipases present in adipose tissue
responsible for breaking down triglycerides into one glycerol molecule and three fatty acid molecules
the glycerol molecule is used specifically in gluconeogenesis
31
the secondary site of stored energy
adipose tissue
32
Hormone Sensitive Lipase
activated by glucagon to cleave TAGs
33
ketone bodies
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
34
the alternative source of energy of tissues other than the liver during fasting and especially during starvation
ketone bodies
35
proteins in the fasting state
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
36
urea cycle
conversion of ammonia, which is toxic, into urea and then the urea is excreted by the kidney through urine
37
metabolic changes that occur as bodies transition from the fasting to the starved state
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
38
the length of time in which we can undergo starvation is dependent on what
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
39
vitamin B9
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
40
folic acid deficiency
probably the most common vitamin deficiency in the US, particularly among pregnant women and individuals with alcoholism
41
folic acid function
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
42
nutritional anemias
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
43
anemia
a condition in which the blood has a lower than normal concentration of hemoglobin, which results in a reduced ability to transport oxygen
44
Microcytic anemia
MCV is below normal, and is caused by a lack of iron
most common form of nutritional anemia
45
macrocytic anemia
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
46
what can cause inadequate serum levels of folate
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
47
a primary result of folic acid deficiency
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
48
most common neural tube defects (NTDs)
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
49
folic acid dose for women of childbearing age
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
50
vitamin B12
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
51
cobalamin deficiency
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
52
cobalamin structure
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
53
the physiologic coenzyme forms of cobalamin
5′-deoxyadenosylcobalamin (cyanide is replaced with 5′-deoxyadenosin)
methylcobalamin (cyanide is replaced with a methyl group)
54
cobalamin distribution
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
55
folate trap hypothesis
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.
56
in which cells are the effects of cobalamin deficiency most pronounced
in rapidly dividing cells, such as the erythropoietic tissue of bone marrow and the mucosal cells of the intestine.
57
clinical indications for cobalamin
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
58
the Schilling test
evaluates B12 absorption
59
pernicious anemia
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)
60
pernicious anemia treatment
requires lifelong treatment with either high-dose oral B12 or intramuscular injection of cyanocobalamin
61
cobalamin absorbtion pathway
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
62
transcobalamin
binding protein for B12
63
vitamin A
a fat-soluble vitamin that comes primarily from animal sources as retinol (preformed vitamin A), a retinoid
64
retinoids
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
65
retinoic acid
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
66
retinal
the aldehyde derivative of retinol which mediates the actions of the retinoids for vision
67
retinoids structure
include the natural forms of vitamin A, retinol and its metabolites, and synthetic forms (drugs)
68
retinol overview and structure
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
69
retinal structure
the aldehyde derived from the oxidation of retinol
retinal and retinol can readily be interconverted
70
retinoic acid structure
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
71
β-Carotene overview structure
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.
72
vitamin A absorption
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
73
fat-soluble vitamins carrier
all fat-soluble vitamins are carried in chylomicrons
74
vitamin A release from liver
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
75
retinoic acid mechanism of action
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
76
retinoic acid receptors (RARs)
specific receptors found in the nucleus of target cells which bind with high affinity to retinoic acid
77
activated retinoic acid–RAR complex
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
78
vitamin A functions
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
79
rhodopsin
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]
80
when rhodopsin is exposed to light
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
81
regeneration of rhodopsin
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
82
vitamin A distribution
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)
83
RDA for vitamin A
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)
84
vitamin A deficiencies in vision
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
85
xerophthalmia
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
86
night blindness
nyctalopia; can be caused by a vitamin A deficiency
87
tretinoin
all-trans retinoic acid which is used to treat mild cases of acne and skin aging topically
88
isotretinoin
13-cis retinoic acid which is administered orally to treat severe cystic acne
89
retinoid toxicity threshold
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
90
early signs of chronic hypervitaminosis A
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
91
hypervitaminosis A in pregnancy
excessive quantities of vitamin A has potential for teratogenesis (causing congenital malformations in the developing fetus)
92
vitamin D
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
93
most prominent actions of calcitriol
to regulate the serum levels of calcium and phosphorus
94
calcitriol
1,25-dihydroxycholecalciferol ([1,25-diOH-D3]
the active molecule of vitamin D
overall function is to maintain adequate serum levels of Ca2+
95
7-Dehydrocholesterol
an intermediate in cholesterol synthesis which is converted to cholecalciferol in the dermis and epidermis of humans exposed to sunlight
96
cholecalciferol
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
97
ergocalciferol
vitamin D2, found in plants
source of preformed vitamin D activity
98
cholecalciferol
vitamin D3, found in animals
source of preformed vitamin D activity
99
Vitamin D2 and Vitamin D3 chemical difference
differ only in the presence of an additional double-bond and methyl group in the plant sterol
100
1,25-Dihydroxycholecalciferol formation overview
vitamin D2 and D3 are converted in vivo to calcitriol by two sequential hydroxylation reactions performed by cytochrome P450 proteins
101
the first hydroxylation during calcitriol formation
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
102
calcidiol
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
103
25-hydroxylase
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
104
the second hydroxylation during calcitriol formation
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)
105
25-hydroxycholecalciferol 1-hydroxylase
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
106
calcitriol formation regulation
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
107
how calcitriol maintains adequate serum levels of Ca2+
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
108
calcitriol path in the intestine
(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
109
calcitriol effect on bones
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+
110
vitamin d distribution
occurs naturally in fatty fish, liver, and egg yolk. Milk, unless it is artificially fortified, is not a good source
111
vitamin D RDA
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
112
nutritional rickets
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
113
renal osteodystrophy
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
114
hypoparathyroidism
lack of PTH causes hypocalcemia and hyperphosphatemia. (PTH increases phosphate excretion)
patients may be treated with vitamin D and calcium supplementation.
115
vitamin D toxicity
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
116
vitamin K1
also known as phylloquinone, an active form of vitamin K which exists in plants
117
the principal role of vitamin K
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
118
vitamin K2
also known as menaquinone, an active form of vitamin K, which exists in intestinal bacteria
119
menadione
a synthetic form of vitamin K which is able to be converted to K2 (menaquinone)
120
γ-Carboxyglutamate (Gla) function
required for functional versions of the coagulation factors prothrombin, FVII, FIX and FX
121
γ-Carboxyglutamate (Gla) formation
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
122
γ-glutamyl carboxylase
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
123
warfarin
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)
124
vitamin K epoxide reductase (VKOR)
the enzyme required to regenerate the functional hydroquinone form of vitamin K
125
γ-carboxyglutamate (Gla) residues role within coagulation enzymes
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
126
vitamin K distribution
found in cabbage, kale, spinach, egg yolk, and liver
there is also synthesis of the vitamin by the gut microbiota.
127
vitamin K RDA
the adequate intake for vitamin K is 120 μg/day for adult males and 90 μg for adult females
128
vitamin K deficiency generally
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
129
vitamin K deficiency in newborn
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.
130
vitamin K toxicity
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
131
the E vitamins composition
consist of eight naturally occurring tocopherols, of which α-tocopherol is the most active
132
vitamin E function
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)
133
vitamin E distribution
vegetable oils are rich sources of vitamin E, whereas liver and eggs contain moderate amounts
134
RDA for α-tocopherol
15 mg/day for adults
the vitamin E requirement increases as the intake of polyunsaturated FA increases to limit FA peroxidation
135
vitamin E deficiency in newborns
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
136
vitamin E deficiency in adults
usually associated with defective lipid absorption or transport
137
abetalipoproteinemia
caused by a defect in the formation of chylomicrons [and VLDL], results in vitamin E deficiency
138
clinical indications for vitamin E
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
139
vitamin E toxicity
the least toxic of the fat-soluble vitamins
no toxicity has been observed at doses of 300 mg/day
140
marasmus
141
kwashiorkor
142
mixed marasmus-kwashiorkor
these children often have concurrent wasting and edema in addition to stunting. These children exhibit features of dermatitis, neurologic abnormalities, and fatty liver.
