1
Q
PTH, Vitamin D and P Regulation
A
- When [P] in the blood is low:
- Stimulates 1,25(OH)2-VitD3 production
- Decreases PTH secretion
-decreases serem [P] - When [P] in the blood is high
- Increases PTH secretion and decreases 1,25(OH)2-VitD3 production
- **PTH decreases renal resorption of P**
-decreases serum P
2
Q
Ca: P ratio imbalances
A
- Excessive dietary P can interfere with Ca2+ absorption in the small intestine.
- High dietary phytate can be problematic, found in plants
- Phytate is a mostly insoluble, phosphate rich plant compound that binds dietary
cations (iron, zinc, calcium and magnesium), preventing absorption. - High dietary P levels leads to large fecal losses and bone resorption
-ratio should be Ca:P 1:2 between 2:1
3
Q
Ca2+ sources
A
- Normally insufficient in plant sources
- To get a balanced Ca2+ -P ratio in diets, normally add:
1. Meat meal for protein/P
2. Dicalcium phosphate for P
3. Limestone or calcium carbonate (oyster shells) to balance Ca2+ :P ratio - Can use bone meal for P; has some Ca2+ , but is mostly useful as a P
source - Ca2+ is cheap; P is expensive
4
Q
Ca2+, Vitamin D, Phosphorus Deficiency
A
- Rickets in young; osteomalacia in
adults - Osteomalacia and poor
pigmentation in older animals - Abnormalities of erythrocytes,
leukocytes and platelets - Pica where animals consume dirt,
chew on pen materials
5
Q
cage layer fatigue
A
- Occurs in laying hens at peak production
- Due to high requirement for Ca2+ for egg shell formation
- Causes bone deformities, fractures and paralysis
- Pullets should be fed high Ca2+ to build up reserves and proper Ca2+ ,
P and Vitamin D levels should be maintained in the diet
6
Q
Ca, P and vit D toxicity
A
- Ca toxicity does not occur normally: Excess Ca2+ is simply not absorbed
- P toxicity is rare: Usually due to kidney failure
- Vitamin D leads to:
- Calcification of soft tissue
- Hypertension
- Renal failure
- Avoid megadoses of vitamin D
7
Q
phosphorus functions
A
- As phosphate (PO43-), it is the most abundant intracellular anion
- Structural: P is an essential part of bone mineral (75-85%)
- Component of cell membranes (phospholipids)
- Metabolic: ATP, RNA, DNA, NADP etc.
- Free phosphate liberated for energy from ATP
- Phosphate intestinal absorption:
- Passive paracellular diffusion
- Active transcellular transport
- Active stimulated by Vitamin D
- Excretion and absorption regulated by PTH
and Vitamin D
8
Q
functions of Ca
A
- Bone strength and maintenance
- Can contribute to membrane potential (funny current)
-blood clotting cofactor - Serves as 2nd messenger to rely info
from outside to inside the cell - e.g. muscle contraction
-major component of milk
9
Q
Absorption of Ca2+
A
- Active, transcellular absorption
* Upregulated to increase Ca2+ absorption when body Ca2+ stores are low - Passive, paracellular absorption
* Occurs all the time
* Passive diffusion, so rate is dependent on
dietary Ca2+ concentration
10
Q
Passive paracellular absorption of Ca2+
A
- Occurs:
- In the jejunum and ileum
- When dietary calcium levels are moderate or high
- Ca2+ diffuses through tight junctions into the basolateral
spaces around enterocytes, and into blood - Up to 50% of absorption in monogastrics
- Less important in ruminants because rumen dilutes Ca2+ in digesta
11
Q
Active transcellular absorption of Ca2+
A
- Occurs
- In the duodenum
- Up regulated when body Ca2+ stores are low
- Process has 3 steps
1) facilitated diffusion of calcium into the enterocyte
2) transport across the enterocyte
3) active transport into extracellular fluid (ATP > ADP)
-regulated by calbindin carrier which vitamin D activates the synthesis of calbindin
12
Q
Factors Affecting Ca2+ Absorption
A
Absorption is inhibited by compounds that form insoluble Ca2+ salts
* Oxalates, phytates and phosphates all form insoluble salts
* Undigested fats form Ca2+ soaps
- A large part of ingested Ca2+ is not absorbed and is excreted in
feces (low digestibility)
13
Q
vitamin K
A
- Vitamin K is a cofactor in the enzymatic
production of Gla (serum prot) which Ca is a cofactor - Vitamin K deficiency can reduce bone
density and cause osteoporosis - Vitamin K needed for y-carboxylation and
activation of osteocalcin
vit K poisoning: * Warfarin and dicoumarol interfere with regeneration of vitamin K by inhibiting its reductase
* Leads to deficiency of active vitamin K
14
Q
Vitamin K Deficiency
A
- Human newborns have no stores of Vitamin K
- If a supplement is not provided hemorrhagic disease of newborns can result
- Human babies usually given a 1 mg injection of vitamin K at birth
- Deficiencies rare in ruminants and most non- human monogastric species
- Deficiency leads to spontaneous hemorrhages in chickens and pigs
15
Q
Sources of Vitamin K
A
- Plants and bacteria
- Intestinal synthesis is important; ruminants don’t normally require
additional Vitamin K - High levels of feed antibiotics may reduce Vitamin K synthesis
- Synthetic source: menadione
- Synthetic Vitamin K susceptible to oxidation if exposed to sunlight, moisture, choline or trace elements
16
Q
Ca2+ Excretion
A
- Kidney - excreted by this route
when [Ca2+] in serum is high;
tightly regulated - Secretion into intestinal lumen
when calbindin is downregulated
(epithelial cells are sloughed and
unabsorbed Ca goes with them) –
fecal excretion - Sweat (small amount)
17
Q
Regulation of Body Ca2+
A
- 99% of Ca2+ in bones and teeth: Hydroxyapatite
- Bone resorption changes with Ca2+
- Osteoclasts remove Ca2+-P from bone
- Osteoblasts deposit Ca2+-P in bone
levels regulated by:
-PTH secreted when Ca is low, fast effect increases glomerular reabsorption, decreases Ca secretion
-slow effect PTH: stimulates vit D in kidney, which increases Ca absorption in intestine, and increases the Ca release from bones (osteoclasts)
-also Vit D, calcitonin and estrogen
18
Q
Vitamin D regulation of Ca/ P
A
- Increases Ca2+ absorption
- Induces gut epithelial calbindin expression
- Increases P absorption
- Stimulates synthesis of collagen and other bone matrix proteins by osteoblasts
- Stimulates bone resorption by osteoclasts and stimulates osteoclast recruitment
- Net effect is higher blood Ca2+ concentrations
-vit D can be activated by UVB UV rays
19
Q
calcitonin and estrogen in Ca regulation
A
Calcitonin:
* Important in fish
* Relatively unimportant in terrestrial animals
* Has the opposite effect of PTH
Estrogen:
* Regulates osteoclast and osteoblast populations
* When estrogen levels low, more bone resorbed; can lead to osteoporosis
* Supplemental estrogen prevents osteoporosis in postmenopausal women
20
Q
energy associated vitamins
A
- Thiamin, Riboflavin, Niacin, Pantothenate, Biotin
- Involved extensively in CHO, AA and lipid metabolism as components
of coenzymes - These B vitamins act as coenzymes or cofactors, body needs for enzymes to work
21
Q
Thiamin or Thiamine
A
vitamin B1
* Active thiamin is thiamin diphosphate (TPP)
* Thiamin diphosphate is a coenzyme in reactions involving removal of CO2
-in prot metabolism, TCA cycle,
22
Q
Thiamine Deficiency
A
- Neural disorders
- Lack of thiamine causes brain damage (star gazing chick, balance loss and siezers in people)
- Beriberi
- Common in SE Asia because of polished rice diets (human diet lacks thiamine and riboflavin. leads to human infant mortality and cardiomyopathy.
in ruminants:
* High sulfate water destroys thiamine causing polioencephalomalacia
(PEM) characterized by cerebral
necrosis
* Signs of PEM are disorientation and
wandering, blindness and
opisthotonos (retraction of the head)
23
Q
riboflavin
A
-vitamin B2
* Functions as coenzyme to two electron
transport reactions:
* FAD to FADH2 (Complex 1)
* FMN to FMNH (Complex 2)
* Crucial for glucose & fatty acid
oxidation, TCA cycle
24
Q
Riboflavin Deficiency
A
- Relatively common vitamin deficiency
- Low in cereals and legumes used for most
monogastric diets - Requirement increased with high fat diets
- Deficiency not life threatening conditions
- Symptoms include:
- Stomatitis
- Cheilosis
- Glossitis
- In chickens causes curled-toe paralysis
25
Niacin
-vitamin B3
* Tryptophan (Trp) can be converted into
nicotinamide and can replace some of
the requirement for niacin
* pathway is very inefficient, especially in poultry.
-sometimes need to add niacin to ruminant diets when using urea
-can give high doses in people to lower LDL cholesterol
26
Niacin deficiency
Causes pellagra in humans
* 4 d’s diarrhea, dermatitis, dementia and death, rough skin
* To produce a niacin deficiency requires a diet low in niacin and tryptophan =Corn based diet
27
Pantothenic Acid
* Vitamin B5
* Pantothenic acid is part of Coenzyme A
* Needed for protein catabolism to produce oxaloacetic acid
* Needed for Acetyl CoA production from either glucose or fats
* Needed in TCA cycle
28
Pantothenic Acid Deficiency
* A deficiency of pantothenic acid
results in impaired fat synthesis
* Deficiency symptoms include:
* Dermatitis
* Goose-stepping
29
Biotin
* Vitamin B7
* Functions as a CO2 carrier in carbon
dioxide fixation and decarboxylation
* Biotin required for protein catabolism
* Biotin required by fat synthesizing
enzymes
* Polyunsaturated fatty acids increase
biotin requirements
* Wheat-based diets have low biotin
availability
30
biotin defiiency
Biotin Deficiency
* Hair-loss, dermatitis and foot cracking, depression, hallucinations and muscle pain
* Raw egg whites contain a protein called avidin which binds biotin making it unavailable to the host
31
Choline
* Important for synthesis of key signaling molecules in body:
* Phosphatidyl choline in cell membrane
* Lipid transport
* Neurotransmitter acetylcholine
* Acts as a methyl donor group in SAM
pathway after conversion to betaine
32
Choline Deficiency & Toxicity
* Fatty liver (puppies), increased blood
prothrombin times, thymic atrophy,
decreased growth, anorexia, peritubular infiltration in liver (cats)
* Egg yolks, glandular meals and fish are rich in choline
* Toxicity: Rare, but reports of anemia with only 3x dietary requirement in dogs
33
Carnitine
* L-carnitine important for fatty acid
shuttling across inner mitochondrial
membrane and β-oxidation
* Found in animal tissue, meat
ingredients
Carnitine Deficiency rare
* Muscle weakness, fasting hypoglycemia,
cardiomyopathy, hepatomegaly, dicarboxulic aciduria
34
Absorption of Microminerals
* Most microminerals form salts and other compounds which are
relatively insoluble (I and Se are exceptions)
* Not readily absorbed
* Minerals often require carrier proteins
* Synthesis of these proteins is important in regulation of mineral
metabolism
35
chelation
* Metal ions are reactive
* Must be chelated to prevent oxidation in the body
* Metals form complexes with a well defined number of organic
ligands (proteins and AA)
36
Storage of minerals
* Most minerals have significant storage so deficiency will not occur
unless absent from diet from weeks to years (Exception Na and K)
* Macrominerals (Ca, P, Mg) stored in bones
* Microminerals (Fe, Cu, Zn, Se, Cr and others) stored in liver often
associated with specific storage proteins
37
Water soluble Vitamins
* All B vitamins are absorbed passively at high levels in the gut and by
sodium-dependent active transport at low levels in the gut (Exception
B12)
* Excesses are excreted in the urine
* Toxicity is rarely a problem
* Storage is limited (apart from B12) and they must be provided
regularly
38
Water soluble Vitamins
Monogastrics vs Ruminants
* Rumen bacteria can synthesize B vitamins and vitamin K
* Production of B-vitamins by microbes in the rumen exceeds ruminant
requirements
* Monogastrics do have some production of B-vitamins in the ceca and
hindgut but absorption in hindgut is limited
39
fat soluable vitamins
* Four fat-soluble vitamins (Vitamins A, D, E and K)
* All are handled by the GI system in the same was as dietary fat
* After absorption fat-soluble vitamins transported to liver in chylomicrons
* Fat-soluble vitamins can be stored unlike water soluble vitamins
* Vitamins A, D and K stored in liver
* Vitamin E stored in adipose tissue
-the body cannot store excess so toxicity can occur.
* Vitamin D is not a true vitamin; hormone involved in regulation of calcium/phosphorus metabolism
* Not excreted in urine; appear in bile and excreted in feces
40
Groupings of Vitamins and Minerals
* Electrolytes (Na, K)
* Bones (Ca, P, Mg, Vit D, Vit K)
* Energy releasing vitamins (Thiamin, Riboflavin, Niacin, Pantothenate,
Biotin)
* Hematopoetic (Folate, B12, Fe, Cu)
* Antioxidant (Vit E, Vit C, Se)
41
electrolytes
* Maintain osmotic and electrolytic environment in body fluids: Maintains protein function
* Maintain a Na/K gradient between intracellular
and extracellular environment
* Important in nerve and muscle function
* Transport of molecules across cell membrane
* Concentrations of electrolytes (primarily K and Na) are maintained at defined levels in intra and extracellular fluids
42
Electrolyte deficiency/ tox symptoms
* Na: Lethargy, loss of appetite, muscle weakness, respiratory
depression and arrest
* K: Elevated blood pressure, muscle weakness, respiratory depression
and cardiac arrest
Electrolyte toxicity symptoms
* Na: Dehydration, seizure, coma
* K: Cardiac arrhythmia and death
43
reactive oxygen species ROS
-O2 superoxide, hydrogen peroxide, hydroxyl peroxide, ect.
* Oxidative stress = when antioxidant
defenses are insufficient to neutralize all ROS
44
antioxidants
-free radical scavengers
* Chemicals that prevent the transfer of electron from O2 to organic molecules
* Preferentially accepts unpaired electron from free radicals
* Terminates free radical reaction
45
Antioxidant Enzymes
* Superoxide Dismutase (SOD)
* Converts superoxide produced from
electron transport chain to hydrogen
peroxide
* Glutathione peroxidase (Selenium) and catalase (Fe) convert hydrogen peroxide to H2O + O2
46
selenium
-narrow range from theuraputic to tox
Se metabolims:
* Se-Methionine is actively absorbed same as Met, absorbed in the SI (no digestion in rumen)
-levels excreted in urine
functions:
- Component of a single enzyme called glutathione peroxidase
* Enzyme degrades peroxides formed during tissue fat oxidation
* Closely associated with Vitamin E
47
Se-Deficiencies (or Vit E deficiency)
* White muscle disease (nutritional muscular dystrophy):
* Infiltration of the muscle tissue by connective tissue which
causes white streaks (calves and lambs)
* Mulberry heart disease:
* Pigs develop malformed heart, sudden death may occur
* Stiff lamb disease:
* Stiff gait, arched back
* Exudative diathesis:
* Young chicks develop severe edema due to poor capillary integrity
48
Selenium Toxicity
* In oviparous vertebrates (fish and birds), Se- Met and Se-Cys incorporated into egg yolk protein: * Causes spinal, skeletal and cardiac deformities,
cataracts
* In non-oviparous vertebrates, see the
following toxicity instead:
* Hoof problems (brittle nails)
* Hair loss
49
vitamin E
* It is an antioxidant which helps to protect cell membranes from damage by radicals
* Main function is as a chain-breaking antioxidant
* Scavenges free radicals for excretion in the urine
*slows the aging process
-major role in stopping lipid peroxidation.
* Deficiency leads to fragile red blood cells, reduced fertility
-stored in adipose tissue
50
vitamin C
* Also known as ascorbic acid
* Acts as a free radical scavenger
* Can be endogenously synthesized from glucose in
animals or obtained from green/citrus plants
* Vitamin C necessary cofactor for several hydroxylase enzymes that synthesize or aid:
* Collagen
* Carnitine
* Co-administration of Vitamin C aids iron absorption
Deficiencies & Toxicities
* Scurvy in humans
* Uncommon in animals due to endogenous synthetic capacity
* Toxicities uncommon
51
Hematopoetic Vitamins and Minerals and functions
-Folic acid, Vitamin B12 and Fe
* Both vitamins are involved in single carbon transfers as catalysts
-Fe is involved in oxidation reduction reactions and heavily involved in red blood cell metabolism
-Fe is a key component of hemoglobin that enables its oxygen binding capacity
* Aerobic metabolism would be impossible without Fe in
hemoglobin
* Fe is also a key component in myoglobin which draws oxygen
from hemoglobin in the blood to muscle tissue
52
Vitamin B12: Cyanocobalamin
* B12 is synthesized by bacteria and yeast: B12 absent in plant products
-B12 is required for methionine synthase.
* Conversion of homocysteine to
methionine requires both B12 and Folate
- If B12 is deficient it breaks the
folate cycle
* Folate and B12 deficiencies look
similar
* Tell difference by administering
folate
* If folate deficiency was cause,
animal will be better
* If B12 was the problem, folate can’t
be recycled and symptoms persist
53
B12 Deficiency
* B12 deficiency results in pernicious or megaloblastic anemia (large, immature RBCs in the blood)
* B12 deficiency occurs as a heritable condition called
Sprue in humans caused by a lack of intrinsic factor
* Ruminants benefit from cobalt supplementation so that
rumen microbes can synthesize B12
54
Folic Acid
* Vitamin B9
* Required for methionine & DNA synthesis
* Abundant in plant sources including
forages
-deficiency:
* Megaloblastic anemia
* Folate deficiency is the most common B-vitamin deficiency in humans in North America
* In early pregnancy in humans folate deficiency can result in neural tube defects (spina bifida)
* In animals, causes anemia, stunted growth, weight loss, increased clotting time
55
Biochemical Functions of Fe
Important hemoproteins:
* Oxygen transport
* (hemoglobin and myoglobin)
* Electron transfer
* (Cytochromes A, B and C – needed for ATP production)
* Metabolism of O2 and peroxides:
* Cytochrome P450 (hormone synthesis and drug metabolism)
* Catalase (degrades H2O2)
* Redox enzymes
56
iron handling in animals
* Iron reduced to Fe2+ in acid environment of stomach
* Intestinal absorption is poor (2-5% can only be absorbed as Fe2+
* Regulation of DMT1 synthesis controls Fe absorption
* Fe2+ is released to Ferritin in cell and transported to the basolateral membrane.
* Feroportin tranports Fe2+ across the basolateral membrane
* Transferrin transports iron in plasma, then ferritin stores iron in liver, spleen and bone marrow cells
57
Lactoferrin – normal function and during infection
* Two main functions
1. Excreted in milk to bind iron in gut of neonates
2. Prevent bacterial infections
* During an infection, secreted by liver:
* Binds iron in the body and returns it to the liver where it is stored as ferritin
* Reduces availability of Fe to bacteria
* Competition between host and bacteria for Fe
-animals have developed defenses to withhold Fe from bacteria via lactoferrin
* Lactoferrin also possesses direct anti-microbial and anti-inflammatory properties
58
iron toxicity
-Iron overload is rare in animals
* Causes anorexia, weight loss, decreased serum albumin, hepatic dysfunction and
hemosiderosis when overloaded
* Hemochromatosis is a genetic disease
in humans where iron is over-absorbed
from the diet
* Causes joint pain, liver disease, heart
abnormalities
*Iron content of oilseeds and pulses is higher than cereal grains
*Forage iron is relatively unavailable
*Animal source Fe is highly available
59
iodine
* Absorbed by the small intestine by passive diffusion
* Highest concentration of iodine is in the thyroid
* Sources of iodine in feed are highly variable and depend on soil iodine
levels
* Functions:
1. Iodine is a component of the hormones triodothyronine (T3) and thyroxin
(tetraiodothyronine T4)
2. These hormones control basal metabolism including: thermoregulation,
intermediary metabolism, reproduction, growth and development
deficiency: goiter thyroid or caused by brassicas and goitrogens
60
chromium
* Cr is involved with CHO, lipid, protein and nucleic acid metabolism
* Cr works as a cofactor with insulin
* Chromium is known to promote insulin activity and enhance CHO metabolism in pigs
* Insulin promotes anabolic processes (molecule assembly) and inhibits
catabolic processes
* This metabolic activity has the net effect of promoting protein synthesis
(muscle growth) while inhibiting fat deposition
61
Chromodulin & Insulin
* Cr is a cofactor in insulin
* Cr utilization depends on its:
* Valence- Cr3+ is utilized, while Cr6+ is not
* Chemical form: organic Cr is used while inorganic Cr is no
* Binds 4 chromium ions for maximal
activity
* Potentiates insulin activity without
changing insulin concentration
62
chromium and pig production / sources
Cr supplemented pigs had:
* Better feed conversion
* Improved carcass traits
* Increased carcass lean
* Increased loin muscle area
* Reduced tenth rib backfat thickness
Inorganic Cr is not well absorbed
from the small intestine
* Absorption is higher from chelated
Cr
* Chelated Cr sources include
* Chromium picolinate
* Chromium yeast
63
vitamin A
* Vitamin A: Retinol, retinal, retinoic acid
* Provitamin A: carotenoids: Found in plant products
Vitamin A requirements are defined in retinol equivalents (RE)
* 1 RE = 1 μg of all-trans retinol
Bioavailability of Carotenoids:
* Pigs are less efficient in converting carotenoids into usable Vitamin A than poultry
* Vitamin A and carotenes are transported across the gut
epithelium the same as fatty acids: passive diffusion
* In the epithelial cell, carotenes are converted to retinol
64
Vitamin A functions
* Vision
* Retinal needed for rhodopsin function in rods
* Immunity
* Maintains normal skin health by
switching on genes and differentiating
immature skin cells (keratinocytes) into
mature epidermal cell
* Bone health
* Optimal retinoic acids levels needed to
maintain balance between osteoblast and osteoclast activity
* Gene regulation
* Retinoic acid regulates expression of
RXR target genes
* Birth defects: Both vitamin A deficiency and excess
65
Vitamin A deficiency
Classic deficiency is night blindness
* Epithelial keratinization, mucosal membrane atrophy
* Low conception rate and libido
* Decreased immunity
* Generally causes reduced feed intake and growth
66
Vitamin A Toxicity
* The most toxic vitamin**
* At 10x requirement, Vitamin A causes toxicity
* Leads to developmental deformities, skeletal deformation and
fractures in adults, peeling skin, increased intracranial
pressure, hyper-irritability, convulsions and death
* Bear, seal livers are extremely high in Vitamin A and can be toxic
* Carotenoids less toxic, but can lead to yellow-orange skin if
carrots or other high carotenoid foods eaten
animal production
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