nutrition exam 3

What is GLUT4?

• receptors in adipose tissue, released to cell surface in presence of insulin

• when glucose is in excess → GLUT4 binds to glucose and brings into adipose to oxidize to acetyl coa

What is ketone synthesis?

liver takes excess acetyl coa in blood to make acetic acid

• acetic acid → beta hydroxybutyrate

• acetic acid → acetone

What is over conditioned?

Symptoms: decreased intake which causes decreased blood glucose, glucagon production

• glucagon phosphorylates lipase to breakdown triglyceride to fatty acids

• fatty acids go to beta-oxidation to create acetyl coa

• liver converts acetyl-coa to ketones bodies

• beta-hydroxybutyrate goes to tissues/bloodstream

• acetone is respired in the lungs (less harmful)

How to treat severe ketosis?

Under severe ketosis the body needs to generate more oxaloacetate to take acetyl coa into the Krebs cycle

• but since there is decreased intake, not enough OAA is available to compensate for the huge quantities of acetyl coa

• treatment: orally dose with PROPYLENE GLYCOL to generate more oxaloacetate

What is Kwashiorkor?

Protein malnutrition, occurs when the only source of sustenance is high in starch and no protein

• high glucose, liver oxidizes to acetyl coa, acetyl coa carboxylase is activated for fatty acid synthesis

• to export VLDLs out of the liver, apoproteins are required

• NO proteins available → no export of fats out of liver

• formation of triglycerides remain in liver → FATTY LIVER DISEASE

**distended stomach in malnutritional children due to enlarged fatty liver

**can also occur in over consumption of alcohol → cirrhosis of liver

What is brown adipose tissue?

Brown fat is prevalent in all mammals

• fat that generates heat instead of ATP

• contains thermogenin protein

• norepinephrine/cortisol stress hormones trigger mobilization if brown fat

**hibernating animals generate a different variation

What are biological functions of proteins?

• tissue proteins (collagen, elastin)

• keratin (hair, wool, feathers)

• blood proteins (albumins, globulins)

• enzymes

• hormones/growth factors

• immunity

• purine/pyrimidine, histamine, pigment and vitamin synthesis

Why is using protein for oxidative metabolism not the best for agriculture?

1. protein is expensive

2. proteins as an energy source is metabolically inefficient

3. could be a burden on the kidney and liver and potentially lead to organ failure (geriatric companion animals)

4. excess of some amino acids can affect uptake and utilization of other nutrients

Protein digestion in monogastric/lower GI of ruminants

• acid in stomach denatures protein to lose tertiary and quaternary structures

• pepsin hydrolyzes peptide bonds to smaller peptides

• in duodenum, exo/endo-peptidases secreted by pancreases hydrolyze to smaller peptides and free amino acids

• can NOT digest tripeptides → secreted in feces

Amino acid inter-conversion via transamination

Non-essential amino acids (NEAA) can be synthesized by the body with metabolites of biochemical pathways and an “amine” group.

• Interconversion transfers an amine group to a “carbon skeleton”

• alanine + a-ketoglutarate —-transanimase—→ pyruvate + glutamate

• aspartate + a-ketoglutarate —-transaminase—→ oxaloacetate + glutamate

De-amination in the rumen and use of NH3

amino acid —-enzymatic/microbial action—→ a-ketoacid + NH3

1. ammonia can be utilized in the synthesis of NEAAs

2. excess ammonia is absorbed into the blood and taken up by the liver to be converted into urea and excreted by kidney in urine

3. urea can be recycled in saliva (poor protein nutrition)

Absorption of amino acids

• energy requiring active transport in the SI

• high levels of certain amino acids (lysine) can inhibit uptake of other amino acids

Protein synthesis and degradation

• synthesis and degradation is constantly occurring - a never ending process

• “growth” is achieved when the rate of protein synthesis exceeds the rate of degradation

What are macro-minerals?

minerals required in large amounts

• Cations (sodium, potassium, calcium, magnesium)

• anions (phosphorous, sulfur, chlorine)

what are micro (or trace) minerals?

minerals required in small amounts

• primary requirement (iron, copper, cobalt, zinc, manganese, selenium)

• others (fluorine, molybdenum, chromium, silicon, iodine)

What are toxic minerals?

• arsenic

• lead

• mercury

• fluorine

• molybdenum

• selenium

What are endopeptidases?

protein hormones that cleave the middle of peptides

• trypsin

• chymotrypsin

• elastase

What are exo-peptidases?

protein hormone that cleaves the ENDS of peptides

• carboxypeptidase A and B

Peptide and amino acid transport

dipeptides from diet enter IMC along with H+

• H+ is pumped back into intestinal lumen in exchange of Na+

• Sodium potassium pump takes Na+ out of the cell in exchange for K+ across basolateral membrane

Transport of amino acid into other tissues require sodium

• sodium binds to amino acid transporter

• binding of sodium increases carriers affinity

• sodium-amino acid co-transporter forms

• conformational change

• sodium is pumped out of cell with Na/K pump

What is chelate?

A mineral bound to an organic compound, natural occurring or commercially synthesized

• chelates can either enhance or reduce bioavailability of the bound mineral

Role of calcium

Important oxidation state Calcium 2+

• structural component

• muscular contractile activity

• nervous impulse transmission

• second messenger function, critical role in blood clotting cascade

tissue stores: 99% in bone/teeth, 1% in extracellular fluid

Calcium homeostasis - LOW blood calcium

LOW blood calcium → sensed by parathyroid gland (PTG)

• PTG secretes parathyroid hormone (PTH)

  1. PTH signals the kidney to STOP excreting calcium

  2. PTH also signals long bones to mobilize calcium into the blood = resorption

  3. PTH also increases hydroxylase to add an OH group to vitamin D to convert it to its active form

• vitamin D tells the IMC to upregulate calcium binding proteins to absorb more calcium form the diet

Calcium homeostasis - HIGH blood calcium

High blood calcium is sensed by the THYROID GLAND

• thyroid glands secrete calcitonin

  1. calcitonin signals the kidneys to excrete calcium

  2. calcitonin will inactivate hydroxylase → no more active vitamin D

  3. calcitonin shuts done resorption of long bones

Absorption of calcium

A variable depending on age and presence of chelating agents

• initiated by parathyroid hormone via upregulation of calcium transport proteins in IMC

• increased formation of vitamin D3 → which decreases kidney excretion of calcium, enhance bone resorption

Calcium deficiency

Lack of calcium, phosphorous OR vitamin D3 results in weak bones

• Osteoporosis = reduction in bone mass with tendency to fracture

Calcium in animal nutrition

Laying hens require the HIGHEST calcium % in ration of any animal

• laying hens need ~4% calcium in diet for eggshells

• dairy cattle → calcium deficiencies = “milk fever”, Parturient Paresis

What is “Milk Fever”

Calcium deficient cows after they give birth.

• high colostrum production causes a significant draw on “pool” calcium supply

• disorder marked by cold body temp, sluggish behavior, sternal recumbency

• treatment with intravenous calcium gluconate solution → induces muscle spasms, expelling of feces, attempts to stand

• Jersey cows are more prone to milk fever, Holsteins not so much

Best prevention for calcium defiency?

1. high calcium will NOT work!

2. feeding low calcium during the dry period will slightly improve but not enough

3. administer vitamin D3: difficult to manage timing of injections (daily 30 mill units)

4. Dietary cation/anion balance → to induce a systemic acidosis right before parturition, adding anions will decrease incidence of milk fever, bones will give up more calcium during acidosis (**minerals not palatable for cattle)

5. low potassium diet: high potassium blocks the parathyroid gland which makes it ineffective to sense low calcium. Less potassium will ensure that PTG can monitor calcium levels

Calcium toxicity

Excess calcium is excreted in the urine and feces. High dietary calcium can overwhelm the homeostatic mechanism

• osteopetrosis = excessive calcium deposition in bones and soft tissue (muscle and urinary calculi)

• excessive calcium interferes with Zn, Mg, P, Fe, I, MN, Cu utilization

Mineral metabolism: PHOSPHOROUS

Phosphorous does not exist in the free form but as compounds with oxygen PO4 3-.

• P deposits are found in rocks but must be extracted before use in a feed supplement because they contain toxic excessive levels

Phosphorous absorption

Phosphorous is absorbed in the duodenum, amount dependent on:

• source plant vs animal (PHYTIC ACID, concern in nonruminant nutrition)

• Calcium to Phosphorous ratio should never exceed a 1:1 ratio

• intestinal pH

• levels of other minerals (iron, manganese, potassium, magnesium)

• status of body, the greater the need the more efficient the absorption process

• Vitamin D deficiency → less phosphorous absorbed

• regulated by parathyroid hormone, calcitonin, Vit D

Excretion of Phosphorous

Excess phosphorous is primarily excreted in the urine with endogenous P excreted in feces.

Biological role of phosphorous

A major constituent of bone, essential component of organic compounds in tissue metabolism

• muscle

• energy

• carbohydrate

• amino acid

• fat

• nerve

Deficiency or imbalance of Phosphorous

**deficiencies are almost unknown

• fragile, weak bones

• weight loss, emaciation

• reduced feed intake, milk production, repro efficiency

• **Chewing of wood, rocks, bones and other objects = PICA

Toxicosis of Phosphorous

Excess of Phosphorous relative to calcium in ruminants can result in urinary calculi in kidneys or bladder (kidney/bladder stones)

• high blood phosphorous levels result in decreased blood calcium → causes the parathyroid gland to increase resorption of bone stores and increase renal excretion of phosphate

Calcium : Phosphorous nutrition

1. meet Ca and P requirement, Ca : P ratio is worthless if either is deficient

2. develop desired ratio - always have more Ca than P in ration.

• growing animals need 2 : 1, Ca : P

3. avoid excessive levels of both Ca and P - grains are high in P and low in Ca, forages are high in Ca and low in P

Mineral Metabolism: Magnesium (Mg2+)

• 50-60% Mg stores in bones

• remaining in soft tissue

• liver and skeletal cells contain highest concentration of Mg

• significant amounts associated with red blood cells

Magnesium absorption

Precise mechanism of absorption is unknown

• thought to be absorbed in ileum

• proportion of Mg absorbed declines with increasing dietary levels, availability of carbohydrate source (+), presence of organic acids (-)

• high levels of calcium, phosphorous, potassium ADVERSELY affect Mg absorption

Magnesium Excretion

• excreted mainly in urine

• feces (bile salts, pancreatic enzymes, saliva, gastric juice, intestinal secretions)

Biological role of Magnesium

Component of bone and needed for bone development

• “activator” for enzyme systems in protein synthesis, nucleic acid, fats, coenzyme synthesis, neuromuscular transmission

• phosphate group transfer in cellular respiration, oxidative phosphorylation

• “ activator” for thiamine pyrophosphate (TPP) reactions (decarboxylation of a-keto acids)

• associated with mitochondria (oxidative phosphorylation)

Magnesium deficiencies/imbalances

*Uncommon due to generally adequate concentration

• Deficiency in ruminants = “grass tetany” (hypomagnesemia)

• occurs during early spring/late fall, abrupt changes in temperatures → lush, fast growing pastures have soil excesses of P, N or K

• symptoms: nervousness, hyperexcitability, stiff ataxic gait, muscle tremors, hypersalivation

• treatment: magnesium fluids IV

Magnesium toxicosis

Unlikely except by accidental poisoning or administered in high levels.

• lethargy, ataxia, diarrhea, low feed intake, death

Microminerals: POTASSIUM, SODIUM, CHLORIDE

Sodium, chloride, potassium work together in regulating osmotic pressure gradients in intracellular and extracellular fluids, acid-base balance

• Potassium (K+) mostly intracellular

• Sodium (Na+) mostly extracellular

• Chloride (Cl-) extracellular, Cl- and bicarbonate (HCO3-) balance Na+ in extracellular fluids

• Milliequivalents of cations MUST balance the Meq of anions

Biological function of Sodium, Potassium, Chloride

Na+ is the primary cation of extracellular fluids

• Muscle (heart) action and nervous impulse conduction, transmission

K+ (with Na+) influences osmotic equilibrium across membranes

Cl- functions as components of gastric secretions (HCl) to ensure proper fluid-electrolyte, acid-base balance

Absorption of sodium, potassium, chloride

• Sodium and Potassium cross IMC by active transport but by diffusion in stomach

• Chloride is transferred by active processes in stomach and upper intestine, passive diffusion in large intestine

RECYCLING of sodium, potassium, chloride

80% of sodium and chloride arises from endogenous secretions (saliva, bile, GI secretions) so variations in salt intake have small effects

• Diarrhea, skin burns and parasitic loads in GI can interfere with normal absorption

Homeostatic control of sodium, potassium, chloride

• excess dietary intake of any of these 3 will cause increased excretion by kidneys

• plasma sodium levels controlled by hormone aldosterone to increase sodium absorption in kidneys. Natriuretic hormone induces the kidney to excrete sodium and anti-diuretic hormone (ADH) secreted by posterior pituitary

• **if diet is low in sodium, kidney will reabsorb sodium

All above hormones maintains a constant ratio of sodium to potassium, INVERSE relationship between Na/K

Chloride metabolism is controlled in relation to sodium, excess kidney excretion of sodium is accompanied by chloride

• High plasma bicarbonate (HCO3-) = excretion of chloride

Deficiencies in sodium, potassium, chloride

• deficiency in potassium - abnormal electrocardiograms (arrythmia), lesions in kidney tissue. Poor growth, weakness, pica, emaciation. **Lack of Mg will result in failure to retain potassium

• deficiencies in sodium or chloride - reduced growth in growing, weight loss in mature, reduced production in lactating animals. Will display cravings for sodium → drink urine.

• decline in urinary excretion of sodium, decline in urine volume

Toxicosis of potassium, sodium, chloride

• Potassium toxicosis - high potassium interferes with magnesium absorption, can predispose animal to hypomagnesemia tetany.

• Salt toxicosis - increased intake of water , anorexia, weight loss. About 4-9% salt tolerated by cattle/sheep/swine. Only 2% tolerated by poultry.

• Chloride toxicosis - unlikely. Consumption of purified amino acids may decrease acidity of diet.

Macro mineral SULFUR

-2 oxidation state is most important

• sulfur containing amino acids: Cysteine, methionine, cystine (2 cysteine)

• Glutathione

• Thiamin

• Biotin

• Estrogens

• Heparin

• chondroitin sulfate

• fibrinogen

• coenzyme A

**all can be synthesized in vivo from sulfur EXCEPT thiamin and biotin

Biological function of sulfur

• acid base balance

• protein synthesis

• lipid and carb metabolism

• collagen and connective tissue

• blood clotting cascade

• ergothioneine (red blood cell)

• endocrine function

Absorption of Sulfur

Absorption of organic and inorganic sulfur occurs by ACTIVE transport in small intestine.

• absorption is very low for inorganic sulfur

• organic forms are readily absorbed

Excretion of sulfur

Primarily in form of bile if excreted in fecal and urinary fractions

Inter-relationships of sulfur

• Sulfur / Selenium → Selenium (toxic) containing amino acids have a similar structure to sulfur containing amino acids and can compete for reactive sites on enzymes

• Sulfur / Molybdenum / Copper → Tetra thiomolybdate

Deficiency of Sulfur

Inorganic sulfur is not really needed. Shortages of sulfur-containing amino acids can have adverse affects on synthetic and catabolic pathways.

• Ruminants may benefit from inorganic sulfur supplements to be used for the synthesis of sulfur-amino acids

• Sheep and birds require a higher dietary sulfur level because of wool and feathers

Toxicity of Sulfur

Toxicity of ingested sulfur converts to hydrogen sulfide → hydrogen cyanide toxicity