Exam 2 Flashcards
1
Q
Vitamin B6
B6 vitamers
A
Pyridoxine (OH)
Pyridoxal (aldehyde)
Pyridoxamine (NH2, amine)
B6 Vitamins are interchangeable
2
Q
Vitamin B6
5’-phosphate derivative
A
PNP (pyridoxine phosphate)
PLP (pyridioxal phosphate)
PMP (pryidoxamine phosphate)
Function as coenzymes, cannot be absorbed
3
Q
Vitamin B6
Vitamer food sources
A
Pyridoxine: stable, plants (bananas, navy beans, walnuts)
Pyridoxamine and pyridoxal: animals (steak, salmon, light chicken)
4
Q
Vitamin B6
Digestion and absorption
A
Digestion: phosphorylated vitamers dephsophorylated before absorption (small intestinal phosphatases)
Absorption: PN, PL, PM through passive diffusion (71-82% absorbed)
5
Q
Vitamin B6
Enterocyte
A
PN → PNP (pyridixone kinase, ATP)
PL → PLP (kinase, ATP)
PNP → PLP (pyridoxine phosphate oxidase, FMN)
6
Q
Vitamin B6
Blood
A
PLP (60%) along with PL bound to albumin
7
Q
Vitamin B6
Functions
Deficiency: nerve problems
A
Amino acid modification (AA into energy)
Coenzymes PLP and PMP (aspartate → alpha keto acid → OAA + AA, alanine → alpha keto acid → pyruvate + AA)
Decarboxylation neurotransmitters: GABA synthesis from glutamate; serotonin and melatonin
Transfulfhydrations and desulfhydrations reactions (cysteine and pyruvate synthesis)
Cleavage of serine to glycine PLP removes methyl from serine to THF (folate); 5,10-CH2-THF and glycine (thymidine synthesis)
Synthesis of heme, niacin, histamine, carnitine, taurine, and dopamine
Glycogen degradation to store CHO via glycogen phosphorylase → G-1-P
Steroid hormone action prevents hormone binding and diminish steroid action
AA metabolism: PLP of Schiff base (product of AA and aldehyde), alpha C
8
Q
Vitamin B6
Cells
A
Removal of P by phosphatase required
9
Q
Vitamin B6
Liver
A
Stores 5-10%
Phosphorylation (cytoplasm)
PNP and PMP → PLP
PL and hydrolyzed PLP in blood (transport for extrahepatic tissues, muscles)
10
Q
Vitamin B6
PL → PLP
PM → PMP
PN → PNP
A
Kinase (ATP dependent)
11
Q
Vitamin B6
PNP → PLP
PMP → PLP
A
PMP and PNP oxidase (FMN dependent)
12
Q
Vitamin B6
PLP → PL
A
Phosphatase
13
Q
Vitamin B6
Phase I
Function: Transamination
A
Alanine + alpha keto acid → PLP + ALT Alanine + alpha keto acid → pyruvate + AA (glutamate)
14
Q
Vitamin B6
Phase II
Function: Deamination
A
Aspartate + alpha keto acid → PLP + AST Alanine + alpha keto acid → oxaloacetate + AA (glutamate)
Ammonia produced (urea)
15
Q
Vitamin B6
Metabolism and excretion
A
Intracellular PLP controlled by enzymatic hydrolysis (excess → PL through PNP/PMP)
Excess PL → pyridoxic acid (PIC) → urine
Urine PIC = recent vitamin intake
16
Q
Vitamin B6
Interactions
A
Riboflavin: coenzyme (FMN) of PNP/PMP → PLP, aldehyde oxidase + FAD coverts pyridoxal → pyridoxic acid
17
Q
Vitamin B6
DRI, UL, and deficiency
A
DRI/RDA: 1.3 mg/d
UL: 100 mg/d (toxic)
Deficiency (rare): fatigue, cheilosis, glossitis, seizures, convulsions, hypochromic and microcytic anemia (impaired heme)
18
Q
Vitamin B6
Deficiency risk
A
Breastfed infants
Elderly (low intake, accelerated processes)
Alcoholics (PLP conversion impaired)
Maintenance dialysis
Drug therapies (isoniazid, corticosteroids, anticonvulsants)
19
Q
Vitamin B6
Toxicity
A
UL: 100 mg/d
Toxic in pharmacological amounts - no longer recommended
Chronic ingestion of 2-6 g peridoxine → sensory neuropathy
Treats variety of conditions (PMS, atherosclerosis, carpal tunnel, depression, muscular fatigue)
20
Q
Vitamin B6
Assessment of status
A
Erythrocyte transaminase index (enzyme activity)
Plasma PLP concentration
Presence of xanthurenic acid (urine)
21
Q
Vitamin B12
B12 compound
A
“Cobalamin”
Group for compounds
Macrocylic ring (corrin)
Cobalt center
Attached to CN, OH, H2O, NO2, 5-adenosyl/adenosylcobalamin (coenzyme), or CH3 (coenzyme)
22
Q
Vitamin B12
Sources
A
Animal diets (cobalamin from microorganisms; meat, poulty, fish, shellfish, egg, milk) - vegans at risk
Supplements (cyanocobalamin, hydroxocobalamin, yeast)
23
Q
Vitamin B12
Digestion
A
Cobalamins released from food matrix (polypeptides in food, pepsin release at low pH and HCl production)
Cobalamin interacts with R protein (saliva, gastric juice), and intrinsic factor/IF (parietal stomach cells, glycoprotein)
24
Q
Vitamin B12
Absorption
A
Cobalamin binds to R protein → stomach → SI → duodenum (R protein hydrolyzed, cobalamin released)
Cobalamin binds to intrinsic factor/IF (proximal intestine) → ileum → binds to receptors and absorbed
Passive diffusion (pharmacologic w/o IF production)
Absorption decreases with increased intake (80% to 3%)
Cobalamin inhibited by pancreatic insuffiency and lack of IF
25
# Vitamin B12
Malabsorption
Achlorydia (lack of stomach acid)
Lack of IF
Pancreatic insuffiency
26
# Vitamin B12
Circulation
Cobalamins *bound* to *transcobalamins TC I, II, III* (methylcobalamin and adenosylcobalamin in blood)
Stored in **liver**
Enterohepatic circle
27
# Vitamin B12
Functions
**Enzymatic**: *methylcobalamin* (methionine synthesis from homocysteine in *cytosol*) and *adenosylcobalamin* (*mitochondrial* mutase in propinoyl CoA oxidation)
**Neurological**: development and maintenance of myelin (SAM)
28
# Vitamin B12
Methylcobalamin
| Enzymatic function in cytosol
## Footnote
Add methyl (methyl donor/transfer/remover)
SAM common methyl donor and silences genes
Hcy metabolism
Methionine and THF regeneration
**5-methyl-THF → THF**: methyl group transferred to *cobalmin* and then *Hcy* via methylcobalamin (B12)
**Homocysteine → methionine** (add methyl/CH3)
| **Folate, B12, and B6** work together, folate depends on B12 for 5→5,10
29
# Vitamin B12
Adenosylcobalamin
| Enzymatic function in mitochondria
**Methylmalonyl CoA mutase** converts *L-methylmalonyl CoA* from propinoyl CoA → succinyl CoA
**Methylmalonyl CoA mutase** *propinyl CoA* regereated from odd chain FA and AA (methionine, isoleucine, and threonine)
**Methylmalonyl CoA mutase** in *cobalamin deficiency* (methyl CoA and MMA accumulate → rise in blood and urine)
Excess L-methylmalonyl CoA in urine = deficient
| L-methylmalonyl CoA → TCA succinyl CoA (via methylmalonyl CoA mutase)
30
# Vitamin B12
Metabolism
Whole body turnover: 0.1%/d
31
# Vitamin B12
RDA and UL
RDA: **2.4 microgram/day** (1 microgram may sustain normal people)
Synthetic source for elderly due to high achlorydia
No UL
32
# Vitamin B12
Deficiency
Inadequate absorption mostly
Inadequate intake rare (except vegetarians, vegans, and parts of world) - eat fortified cereals
Occurs in stages - low serum concentration, decreased DNA synthesis, *megaloblastic anemia* (*pernicious = lack of IF*), anemia responds to mega dose of folate (not good idea)
Most common in 50+, elderly, alcoholics, and gastrectomy patients (impaired absorption)
* Achlorydia corrected with synthetic source
* Lack of IF secretion = long term gastric inflammation (autoimmune), gastrectomy and destruction of gastric mucosa (B12 pharmacologic)
* Decreased absorptive surface (ileal resection, celiac and trophic sprue, ileitis)
* Parasitic infections (tape worms)
33
# Vitamin B12
Neuropathy
Undetected B12 deficiency leads to neuropathy (10+ years)
Tingling, numbness, coldness
Motor weakness, ataxia, mental dysfunction
Cause: availability of methionine for SAM (for methylation reactions and myelin maintenance/myelin maintenance neural function)
No response to folate therapy
34
# Vitamin B12
Assessment
Serum B12
RBC changes (more immature, large, nucleated RBC *reticulocytes*)
Elevated urinary methylmalonic acid (MMA)
35
# Folate
Structure
Pteridine + PAPA + Glu (s)
(Pteridine + PAPA = Pterioic Acid)
36
# Folate
Forms
**Oxidized**
**Reduced** (4H can be added to 5-8): tetrahydrofolate (*THF* or *THFA*) and dihydrofolate (*DHF*)
**Mono GLU**: supplements, enriched grains, fortified foods (*more bioavailable than Poly GLU*)
**Poly GLU**: food and tissue, Poly → Mono for absorption/cross membrane, cannot leave cell as Poly
**Single C** attachment at **5 or 10**
37
# Folate
Coenzymes
**Reduced Poly GLU**
* *5-methyl-THF*
* *5,10-methylene-THF*
* tetrahydrofolate (THF)
* 5-formimino-THF
* 10-forymyl-THF
* 5,10-methenyl-THF
**Other coenzymes**
* N5-formyl-THF
* N10-formyl-THF
* N5-formimino-THF
* N5, N10-methenyl-THF
* N5, N10-methelene-THF
* N5-methyl-THF (5-CH3-THF)
| N10-formyl-THF and N5-methyl-THF (5-CH3-THF) abundant in food
38
# Folate
Reactions
**5,10-metheline-THF → 5-methyl THF** is *irreversible* (MTHFR)
**5-methyl THF → tetreahydrofolate (THF)** is *Vitamin B12* dependent (can go back to 5,10)
| Folate would be trapped in 5-methyl form w/o B12
39
# Folate
Food Sources
Green, leafy vegetables
Orange juice
Legumes
Enriched breads and cereals
| Bioavailability: Food 50%, Folic acid supplements (MonoGLU) 85% (*1.7x*)
40
# Folate
Digestion
Hydrolyze food to **Mono GLU**
Conjugases
* Brush border *zinc* dependent (zinc deficiency prevents absorption)
* Chronic *alcohol* diminish absorption
* *pH* sensitive
41
# Folate
Absorption
Transport system
* Carriers (saturable, pH dependent, energy and Na dependent)
* Simple diffusion (high amounts)
Intestinal cells
* Folic acid → THF (via *NADPH* dependent dihydrofolate reductase)
* 4 H added to 5-8
* THF methylated → 5,CH3-THF
42
# Folate
Body
Blood: **mono GLU** (5-methyl-THF)
Liver/tissue: **demethylated, elongated** glutamate tail (*trapped in cells*)
Total body: **11-28 mg** (half in *liver*)
43
# Folate
Functions
Accepts and donates C units
**Nucleotide synthesis (DNA, RNA)** via *5-10 methylene-THF*, purines, and *thymidine*
**Methylation** of *homocysteine → methionine*, *5-methyl-THF*, synthesis of *SAM*
Primary source of methyl: phospholipids, proteins, DNA, and neurotransmitters
44
# Folate
Homocysteine (HCY) → methionine
| Methylation reactions
5-CH3-THF + HCY → methionine + THF*
* **B12** dependent (frees THF)
* Enzyme **HCY methyltransferase**
45
# Folate
Methionine + ATP → SAM
| Methylation reactions
SAM transfers methyl (CH3) to DNA
**DNA methylations turn genes off**
46
# Folate
Sub-optimal folate status
* Inadequate folate intake
* Genetic deficiencies (HCY elevation, MTHFR)
47
# Folate
Disease risk
| Suboptimal intake
CVD (HCY increase)
Neural tube defect
Cancer
Cognitive function
48
# Folate
Relationship with B12
Methyl folate trap (5-methyl-THF trapped w/o B12, THF not regenerated, decreased production of folate coenzymes)
B12 deficiency = megablastic anemia (homocysteine methyltransferase, B12 does not allow for THF to 5,10 to thymidine for DNA)
| Tight relationship
49
# Folate
Metabolism
* Body wants to **hold onto folate**
* Folate **reabsorbed by kidney** and enterohepatic circulation (*little urinary excretion* of intact folate)
* Catabolism between C9 and N10 (pABG excreted in urine)
50
# Folate
DRI
**400 micrograms** of dietary folate equivalents (DFE)
**1 DFE** = **1** microgram natural food, **0.6** microgram synthetic, folic acid (folic acid to DFE, ***1.7x***), 0.5 mcg synthetic on empty stomach (*2.0x*)
| Women consume 400 micrograms to reduce neural tube defects
## Footnote
100 FA x 1.7 = 170 DFE
51
# Folate
Fortification in enriched grains
Prevent neural tube defects
Enriched grains have 140 micrograms per 100 g flour
200 microgram per day to diet (340 DFE)
| Folate deficiency decreased
52
# Folate
Deficiency populations
Elderly
Alcoholics
Inflammatory bowel disease
Malignancies
Pregnant and lactating
Medications (phenytoin, cholestyramine, and sulfasalazine)
53
# Folate
Assessment
Megaloblastic anemia (enlarged immature RBC, decreased DNA, B12 deficiency) - dietitians must assess to see if it is B12 **OR** folate
Low blood folate
Elevated HCY
Altered DNA
54
# Folate
Toxicity
UL: 1000 micrograms
Major concern: masks B12 deficiency (corrects anemia but damages neurology)
Secondary concern: feed cancer and increase tumor growth
55
# Folate
Absorbable forms
Polyglutamate
Reduced, poly GLU
One glutamic acid (no more)
56
# Folate
5,10-methylene-THF
5,10-methylene-THF
57
# Folate
Megaloblastic anemia
Cells cannot divide correctly, not enough folate/B12
58
# Nutritional Genomics
Transcription and translation
Transcription: DNA to mRNA/tRNA/rRNA
Translation: RNA to proteins
59
# Nutritional Genomics
tRNA in action
mRNA code matches to AA and tRNA carrying AA
| Lack of alanine (pairs with pyruvate) - body can create
60
# Nutritional Genomics
Single nucleotide polymorphism (SNPs)
Mutation
A to T changes C to G
| Protein can change
61
# Nutritional Genomics
Human Genome Project (HGP)
Explore all kinds of human and plant genomes
How nutrient and dietary patterns affect health maintenance and disease development
Nutrient and gene interactions
62
# Nutritional Genomics
Genomics
Study of entirety of one's DNA sequence or genome
63
# Nutritional Genomics
Nutritional genomics
**Nutrigenomics** (*different diet affects gene expression similarly on individuals*) + **Nutrigetics** (*gene variance among individuals leads to different nutrient needs*)
64
# Nutritional Genomics
Nutrigenomics
Interaction between dietary components and genome
Resulting changes in gene expression
*Different diet affects gene expression similarly on individuals*
**Nutrients for genes**
## Footnote
Zinc helps gene transcription, Vitamin A in cell differentiation, Energy restriction downgrade metabolism
65
# Nutritional Genomics
Nutrigenetics
Gene variants leads to change in encoded proteins
Affects *nutritional* needs
***Gene variance** among individuals leads to different nutrient needs*
**Gene variations for nutrition needs**
| 5,10-methylene-THF helps form thymidine for DNA and needs MTHFR
## Footnote
PKU, Phe hydroxylase mutation; **MTHFR, C and T polymorphism** variation
66
# Nutritional Genomics
Defected enzyme (MTHFR)
| Nutrigenetics
Methylation impacted because 5,10-methylene-THF excess can contrinue DNA
*Eat more folate for defected MTHFR*
| 65% less
## Footnote
Prevalence: African American higher risk than caucasian
67
# Nutritional Genomics
Mechanisms
Folate inadequacy = carcinogenesis
DNA hypomethylation and cancer genes (677TT) *- eat more folic acid, take genomic/genetic test*
Misincorporation of uracil during DNA synthesis (DNA instability) from 677CC and B12
68
# Nutritional Genomics
Folic acid deficiency and poor methylation diseases
Cardiovascular disease
Neurological diseases
Birth defects
Cancers
69
# Epigenetics
Liver cells (metabolism) versus muscle cell (contraction)
Same DNA
Different function (different genes on and controls)
Cancer is immature cells we do not want
70
# Epigenetics
Nutrition regulate gene expression
Regulatory elements (food) impact DNA sequence to turn on/off structural gene sequence
71
# Epigenetics
Epigenetics
Study of changes in ***gene expression*** caused by mechanisms other than changes in the underlying ***DNA*** sequence
*Methylation DNA turns genes off*
*Bioactive food components inhibit histone deacetylases (HDACs) which may promote tumor suppressor gene expression/cancer*
72
# Epigenetics
DNA methylation
| Adding CH3
Turns off gene
Alters gene expression pattern in cells such that cells can remember or decrease expression
| Dietary factors include alcohol, folate, B12, B6
## Footnote
Cells programmed to be pancreatic islets during embryonic development remain pancreatic islets throughout life
73
# Histone acetylation
Histone (chromatin) modification, acetylation
**De-acetylated** by *HDAC* (positive charge, bound to DNA, turn gene off)
**Acetylated** by HATs (no charge, less bond to DNA, turn gene on)
74
# Epigenetics
Histone deacetylase (HDAC)
Enzyme removes acetyl from histone
Turn gene off
75
# Epigenetics
Sirtuins (SIRT1-7)
| 7 deactylase HDAC
NAD dependent
Animals: NAD precursor, NR or NMN increase SIRT (reduce aging)
76
# Epigenetics
Nonredox reactions and control of NAD levels
| From niacin
Histone deacetylase (HDAC): enzyme removes acetyl group from histone (turn gene off)
Sirtuin (in HDAC): NAD dependent
77
# Vitamin A
Fat solube
Toxic in excess
Liver stored (no deficiency)
Rely on lipids
More stable
| Added to nonfat milk
78
# Vitamin A
Preformed vitamers
Retinol (alcohol)
Retinal (aldehyde)
Retinoic acid (RA)
79
# Vitamin A
Provitamin A
Carotenoids that can be converted to retinol
Beta-carotene (most potent), Beta-crytoxanthin, Lycopene, Canthaxanthin, Lutein
80
# Vitamin A
Plant and animal foods
Plants: beta-carotene to retinal (vision)
Animal: retinyl ester to retinol (reproduction)
Retinal and retinol to retinoic acid (growth, genes, cells) - *cannot convert back*
81
# Vitamin A
Sources
**Free retinol (trans forms) not in food**
* Precursor fatty acid esters
* Retinyl palmitate
* Animal products (yolk, butter, whole milk, liver, fish liver)
**Carotenoids**
* Red, orange, yellow
* Beta-carotene greatest A activity
* *12* micrograms beta-cerotene (*24* micrograms other carotenoids) = **1 retinol activity equivalent (RAE)**
82
# Vitamin A
Digestion and absorption
Often complexed to protein (release pepsin in stomach and proteases in SI)
Release from fatty acid (bile acid, esterases, and lipases)
Release carotenoids and retinols in SI incorporated into micelles
Vitamin A diffuses into enterocyte in proximal SI
70-90% retinol absorbed
20-50% carotenoid absorbed
| Retinol can be acetylated (reesterified) to RE
83
# Vitamin A
Enterocyte digestion and absorption
Beta-carotene to retinal to retinol or RA
Retinol acetylated (reesterified) to RE
Primary pathway for reesterification involves cellular retinol-binding protein (CRBP) II
CRBP II binds retinal and retinol (reduce retinal to retinol, esterification of retinol to retinyl esters, lecithin retinol acyl transferease (LRAT) forms retinyl palmitate)
Nonspecific protein bind retinol in high amounts (reesterification needs acyl CoA retinol acyl transferase/ARAT)
Retinyl esters + unesterified retinol and unchanged carotenoids incorporated into *CM* with cholesterol esters, phospholipid, TGs, apoproteins)
CM enter lymphatic system
Retinal irreversibly converted to *retinoic acid* (*portal blood* and binds to* albumin*)
84
# Vitamin A
Transport
CMs remove RE, retinol, and carotenoids on route to liver by extraheptatic tissues (bone marrow, blood cell, spleen, adipose, muscle, lung, kidney)
CM remnants removed by liver
85
# Vitamin A
Liver
Carotenoids follow 1 of 3 routes
(Cleavage to retinol, incorporated into VLDL, or stored in liver)
Retinyl esters hydrolyzed to free retinol, retinol binds with CRBP, and enzymatic metabolism (LRAT or ARAT, retinol to retinal, retinol to retinyl phosphate)
Retinol not metabolized or transported out (stored as RE in stellate cells)
86
# Vitamin A
Retinol export from liver
Dependent upon synthesis and secretion of retinol-binding protein (RBP)
RBP binds retinol (stellate cells, holo RBP)
Complex secreted to plasma
87
# Vitamin A
Plasma
Holo-RBP interacts with *transthyretin* (TTR)
RBP-TTR complex circulates in plasma
Retinol can be taken to complex
88
# Vitamin A
Cells
Retinoic acid production
| Retinol uptake and retinoic acid production
Retinol to RBP-TRR to Apo-RBP
Retinoic acid binds to CRABP
89
# Vitamin A
Functions
**Visual cycle** (retinal): retinol to retina via RBP-TTR (rod cell), retinol to trans retinal to 11-cis retinal binds to opsin to form rhodopsin
**Cell differentiation** (retinoic acid): DNA sequence, genes ON
Reproduction
Kertain (skin, nails)
Immunity
Bone development
Antioxidants
Growth (lungs, trachea, skin, cornea)
90
# Vitamin A
Interactions
E: cleaveage of beta-carotene, protect substrate
Excess A: inhibit E and K absorption
Protein: transport depends on A
Zinc deficiency: reduce RBP, RBP, ROH
A deficiency: microcytic anemia, iron metabolism, RBC differentiation
91
# Vitamin A
Excretion
Oxidize RA via bile (70% metabolites)
Urinary (30%)
92
# Vitamin A
RDA and UL
RDA: 900 mcg (M) and 700 mcg (F) retinol or RAE
UL: 3000 micrograms (preformed)
12 microgram beta-carotene or 24 microgram other carotenoids = 1 retinol activity equivalent (RAE)
93
# Vitamin A
Deficiency
Developing countries
Mortality (anorexia, retarded growth, infection, keratinization)
Night blindness (rhodopsin in rods, reversible)
Xerophtalamia (conjunctiva and cornea dryness, reversible), Bitot's spots (white sloughed cells)
Corenal ulceration/ketomalacia (soft cornea, irreversible)
| Fat malabsorption, parasites, protein deficit, nephritis, measles
94
# Vitamin A
Toxicity
Dry, itchy skin
Bone and muscle pain
100,000 IU
25,000-50,000 IU/d
Beta-carotene not toxic
95
# Vitamin A
Assessment
Bitot's spots
Dark adaptation
Electroretinograms
Plasma ROH
RDR (reactive dose response) = (plasma ROH at 5 hr - 0 hr) / ROH at 5 hr = >50% = deficit
96
# Vitamin K
2-CH3-1,4-naphthoquione
Plants: phylloquinone (K1), major source
Animals/bacteria: menaquinones (K2)
Menadione: synthetic (K3) to menaquinones in liver
97
# Vitamin K
Absorption
Bile salt
Pancreatic salt
CM
40-80% absorbed
98
# Vitamin K
Sources
Dark green vegetables
Plants
Animal sources
99
# Vitamin K
Blood clotting
Vitamin K needed for post-translational carboxylation for specific glutamic acid residues
Factors II, VII, IX, X
Carboxylated proteins bind calcium
Blood clotting requires conversion of fibrinogen (soluble) to fibrin (insoluble) - catalyzed by thrombin
Thrombin circulates in blood as prothrombin (zymogen inactive)
Prothrombin to thrombin activated by intrinsic or extrinsic pathway
100
# Vitamin K
Transport
CM to liver
VLDL and LDL (liver hepatic)
101
# Vitamin K
Storage
Adrenal gland
Lung
Bone marrow
Lymph nodes
102
# Vitamin K
Cycle
K in carbonxylation is cyclic
Initiated by K reduction to hydroquinone (KH2)
KH2 + glutamic acid + CO2 to carboxylated glutamate residue + K 2,3-epoxide
K 2,3-epoxide reduced to quinone
103
# Vitamin K
Anticoagulant medicine
Warfarin (Coumadin) prevent reduction of K quinone to hydroquinone
Prevent K regeneration (interfere with epoxide reductase)
Atherosclerosis
Ingest more dietary K lead to warfarin resistance
| Avoid K
104
# Vitamin K
Functions
Blood clotting
Synthesis of protein to carry Gla
Bone Gla (osteocalcin) and Matrix Gla dependent on K (MGP)
Kindey Gla protein
105
# Vitamin K
Skeletal tissue
| Vitamin K dependent
Osteocalcin
Synthesis from 1-25-OH2(D3) and RA
Osteoblasts
Gla facilitate Ca binding
Binds hydroxyapatite (bone mineralization)
Deficient - cessation of long bone growth and crystallization
Stimulated by calcitrol (D)
106
# Vitamin K
Interactions
Vitamin A and E interfere
107
# Vitamin K
Excretion
Phylloquinone and menodione into metabolites in urine and feces
108
# Vitamin K
DRI
120/90 micrograms (M/F)
Bacterial synthesis of menaquinones insufficient
109
# Vitamin K
Deficiency
New borns (sterile GI, lack of K in milk, inadequate stores, shot at birth)
Chronic antibiotics (destroy gut bacteria)
Fat malabsorption (liver, gallbladder)
Salicylates, warfarin
| Hemorrhage sign and symptom
110
# Vitamin K
Toxicity
Only menadione (synthetic) combines SH groups = oxidation of membrane phospholipids (hemolytic anemia, hyperbilirubinemia, jaundice)
111
# Vitamin K
Assessment
Prothrombin time (fibrin clot, 11-13 seconds normal, 25+ hemorrhaging)
Plasma prothrombin 80-120 micrograms/mL
Des carboxyglutamyl prothrombin to prothrombin
112
# Vitamin K
DRI
120/90 microgram (M/F)
Bacterial synthesis of menaquinone insufficient
