28 Carb Digestion, Absorption And Metabolism

Oral cavity

Stomach

Small Intestines

Mastication - decrease particle size and increase area for enzyme digestion

Salivary amylase - converts startch to maltose and smaller oligosaccharides (minor in pigs&dogs)

Corpus and fundus

-Salivary amylase converts starch to maltose and small oligosaccharides (esp. pigs)

-enzyme inactivated with low pH

-Pancreatic amylase converts remaining starch and polysaccharides to monosaccharides

Luminal phase - enzymes active in gut lumen

Membranous phase - Enzymes active on surface of the gut

-large polymers (starch, protein)

-Digestive enzymes from salivary, gastric, and pancreatic glands

=breakdown to smaller polysaccharides

-small polymers (polysaccharides, peptides)

-Digestive enzymes synthesized in enterocytes and attached to apical membrane

= breakdown to peptides (monomers for absorption)

**some salivary amylase starts break down**

1. a-alymase is secreted

2. Breaks down large polysaccharides into smaller oligosaccharides (breaks a-1,4 linkages)

3. Dextrinase, Maltase, Isomaltase are secreted

4. Brush boarder breakdown of a-dextrins, maltotriose, and maltose to monosaccharides (glucose)

1. Monosaccharides are picked up by Na+ glucose like transporter (SGLT1)

2. Then secreted by GLUT 2 into portal circulation OR used for gut metabolism

3. Na+ recycled with ATPase

4. Liver (DELIVERY PHASE)

**HIGH concentration of glucose can pass directly though paracellular groove

-Galactose then glucose by lactase

a-glucosidase inhibitors

-acarbose, miglitol

SGLT1

-Kidney, intestine

-Glucose reabsorption in intestine and kidney

SGLT2

-Kidney

-Low affinity - high selectivity for glucose

**SGLT3 is on SI and skeletal muscle for glucose activated Na+ channel

GLUT1: ubiquitous (RBC, Brain, eye, mammary)

-basal glucose uptake

-transport across blood tissue barrier

GLUT2: Liver, kidney, pancreas, SI

-High capacity low affinity transport

GLUT4: Muscle, Fat, Heart

-insulin regulated transport in muscle and fat

GLUT5: Intestine, kidney, testis

-Fructose transport

High luminal glucose concentrations (>25mM)

1. Facilitative Transport (GLUT 1-12)

-fructose tranport (GLUT5) - limited in ruminants

2.Sodium dependent glucose transport (SGLT1-3)

-high affinity, low capacity

-throughout GI tract (increased in jejunum)

-1 glucose + 2 H2O for 2Na+

-rapidly inducible by glucose (high grain)

- Dogs expression of SGLT1 and disaccharidases (sucrase, maltase, lactase) and absorption is greater than CATS

-Ruminant Digestion efficiency: SI (97%) > LI (80%) > rumen (60%)

Foregut (reticulo-rumen and abomasum)

Hindgut (cecum and colon)

Energy for microbes (rumen, cecum and colon) and host

-maintain healthy GI tract!

-FEED -> microbes -> VFA + CH4 + CO2 + microbial cells + long chain FA

-Acetate

-Propionate

-Butyrate (isobutyrate, isovalerate, 2-methyl butyrate)

Slow digestive process of anaerobic digestion by microbial enzymes

Foregut = reticulrumen (ruminants, camels)

Hindgut = cecum, colon (horses, rabbits)

Host: provide environment

-substrate, H2O, pH, oxidation-reduction conditions, slow digesta flow)

Microbes (bacteria, protozoa, fungi)

-convert indigestible material into usable products

-VFA, CH4, NH4, CO2, microbial cells, Long chain FA

1. Substrate - regular supply

2. Microbes - suitable numbers & types (removal comparable with regeneration)

3. Mixing/propulsion - add new substrate & buffers, move contents to abomasum and present inhibitory end product accumulation

4. Fermentation end products - steadily removed

5. Stable intraruminal conditions

1. optimum temperature (37)

2. osmolality 300 mOsm

3. pH ~6.4

4. Anerobic conditions

-negative oxidation-reduction potential

1. Engulf feed particles, digest and store CHO, proteins, and fat

2. Ingest bacteria (keep in check)

3. Produce SOME VFA and NH3

4. Slow down digestion of rapidly fermentable starches and proteins

5.Decrease with high grain diet (pH <5.5)

1. Store starch particles - preventing rapid starch degradation by amylolytic bacteria

2. Reservoir of microbial protein at times of scares/poor feed

3. Digested = provide host with protein, starch and PUFA

1. Free living in Liquid phase

2. Loosely/firmly associated with feed particles

3. Associated with rumen epithelium

4. Attached to surface protozoa and fungi

1. Primary bacteria (feed on digesta)

-cellulolytic: 18h to double (slow metabolism)

-Amylolytic: <4h to double (pH 5.5-6.6) (fast)

2. Secondary bacteria (feed on byproducts) - 16h to double (pH 6.2-6.8)

-Propionate bacteria = utilize lactate

-methanogenic bacteria = utilize H2

1. free bacteria move to fibrous substrate

2. Initial non specific adhesion (electrostatic/ionic) on cut/macerated surfaces

3. Specific adhesion (ligands on bacteria) = proliferation and colonization on feed

DECREASE in digestion of cellulose!! (kills bacteria)

1. Brings enzymes and substrate together

2. Protects enzymes from proteases

3. Allows bacteria to colonize the digestible surface of feed

4. Retention in the rumen to prolong digestion

5. Reduces predatory activity of protozoa

Function: digestion and storage of starch and fat particles

-feed on bacteria

-produce VFA, CO2 and NH3

Storage: feed particle to delay digestion

Location : Both liquid and solid phases

# and size: 10^4-10^6 cell/gm rumen (~51%)

pH sensitivity: highly sensitive (die in grain)

Function: fermenting CHO, fat, protein to VFA CO2 and NH3

Storage: Very limited to none

Location: Free living phase, loosely attached to feed, protozoa and fungi attached

# and size: 10^10-10^12 cells/ gm rumen (48%)

pH sensitivity: some are pH resistant

Starch (amylolytic bacteria pH >5.5) -> glucose

Cellulose (cellulolytic bacteria pH > 6.2) -> glucose

GLUCOSE => fructose 1,6 BisP

Fructosans -> fructose -> fructose 1,6 BisP

Hemicellulose + Pectin -> xylose -> fructose 1,6 BisP

fructose 1,6 BisP -> phosphoenopyruvate (glycolysis)

phosphoenopyruvate (glycolysis) ->

-FORMATE

-ACETATE

-PYRUVATE

FORMATE -> CH4 and CO2

ACETATE -> Acetyl CoA -> Acetoacetate -> B-OH Butyrate -> BUTYRATE

PYRUVATE ->

1. Acetyl CoA -> Acetoacetate -> B-OH Butyrate -> BUTYRATE

2. Lactate -> [direct reductive pathway - propionate bacteria pH >6.2] -> Acrylate -> PROPIONATE

3. Oxaloacetate -> [Randomizing pathway (70-90%)] -> succinate -> PROPIONATE

Microbial (protein) synthesis using stages 1-3 intermediates!!

Amylolytic

-pH >5.5

-15 min - 4h doubling

Cellulolytic bacteria

-pH>6.2

-18h to double

Propionate bacteria

-pH >6.2

-16h double

Decreases (acidic)

Range = 6.5 -> 5.0

1.Diffusion of undissociated short chain fatty acids (HSCFA)

-lipophillic acids (ie. butyric) = efficient

-Acids release protons once inside cell

2.SCFA (acetic, propionic, butyric) transportors

-anions (SCFA-) for HCO3- for apical uptake

-important for less lipophilic acids (acetate)

3.Lactates anions can enter the cell in co-transport with their protons

HCO3-

-imported from the blood via Na+/HCO3- cotransport

-apically-exported HCO3- neutralizes one H+ in the rumen = CO2 + H2O

1. Diffusion of lipophilic and undissociated HSCFA

2. Anion channel permeable to large anions (Cl-) like SCFA- (Cl-/SCFA- antiporter)

3. SCFA-/HCO3- exchanger

4. Metabolized ketone bodies, lactate expelled with protons via monocarboxylate transporter 1 (MCT1)

H+ taken up with HSCFA or lactic acid

= neutralized by HCO3- from basolateral Na+/HCO3- cotransport

= expelled by Na+/H+ exchange (apical or basalateral)

=ATPase on basolateral provides energy form Na+ driven transport

90% Butyrate = kentone bodies (BHBH & acetoacetate) = alimentary ketogenesis

70% Propionate = lactate + CO2 + AA

30% acetate metabolized (fast absorption)

MORE [H+] + [A-]

-Dissociated

-Charged

-Unprotonated

-Free

-Conjugate base (H+ acceptor)

-'Acetate' form

-SLOWLY ABSORBED (some active)

**NORMAL!!

MORE [HA]

-Undissociated

-Uncharged

-Protonated

-Bound

-Conjugate acid (H+ donor)

-'Acetic Acid' form

-RAPIDLY ABSORBED (diffuses across rumen)

Acetate = Phosphoenol pyruvate

Butyrate = Acetyl CoA

Propionate = oxaloacetate and lactate

High forage = A>P>B

High grain = P>A>B

HSCFA = RAPID

H+ + SCFA = SLOW

Rumen = 70%

Omasum = 20%

Intestine = <10%

lactate < acetate < propionate < butyrate

-energy (30% metabolized in rumen epithelium)

-Carbon source for FA - adipose & mammary

-not used for net glucose (no effect on insulin)

- Energy (70% metabolized in rumen epithelium)

- Precursor of glucose (stimulates insulin)

-5% to lactate

-Energy (90% converted to BHBA in rumen epithelium)

-Carbon sourse for FA - mammary

-Not glucose synthesis, but stimulate secretion of insulin and glucagon

-Critical for rumen papillae growth (young calves)

-Increased fermentable carbs causes SLOUGHING of the stratum corneun

= excessive keratinization of epithelium

**PARAKERATOSIS = decreased absorption

Amylolytic bacteria

-Selenomonas ruminatium

-Streptococcus bovis

-Lactobacillus

-S. ruminantium

-S. bovis

-decreases ruminal pH

=inhibits the growth of most ruminal bacteria

=acid tolerant lactobacilli become dominant

-Lactobacilli runimis (produces L (+) lactic acid)

-Lactobacillus vitulinus (produces D (+) lactic acid)

-increase lactic acid producing bacteria

-Decrease lactate utilizing bacteria like M elsdenii and S ruminatium

-Rumenitis (ulcers)

-Liver abscesses (F. necrophorum)

-Diarrhea (increase osmolality of rumen fluids)

-Laminitis

-Death from dehydration, acidosis or endotoxemia

1. Increase in fermentable CHO (pH>6.2)

2. Increase Growth Rate of amylolytic, cellulolytic, methanogenic, propionibacteria, S.bovis, Lactobacillus)

3. Increased VFA production

4. Decreased pH (5.5-6)

5. Increased S. Bovis growth rate (&Lactobacillus)

6. Increased Lactic acid

-Decreases pH

-D/L lactic acid absorbed

- decreases the growth rate which...

-decreases pH more (<5.5)

== INCREASED lactobacillus increases lactic acid

==Decreased S. Bovis

- persistent activation of RR epithelial receptors

-decreased excitation of buccal receptors

1.Inhibition of brain stem, gastric, and salivary centres (decrease bicarb)

2. Stasis in fermentation (decreased motility)

3. D/L lactic acid absorbed

4. METABOLIC ACIDOSIS!!!!

Carbohydrates - glycolysis, glycogenesis, glycogenolysis

Lipids - lipid transport, lipogenesis, lipolysis, B-oxidation

Proteins - AA metabolism, Ureagenesis

1. transport glucose into the cell

2. Glycolysis to pyruvate (aerobic) or lactate (anerobic)

3. TCA cycle and oxidative phosphorylation via ETS = 36ATP/glucose

1. Transport to mitochondria

2. B-oxidation to acetyl CoA

3. TCA cycle and ETS = 129 ATP?palmitate molecule

1. Transamination to generate carbon-skeletons

2. Ketone bodies enter TCA cycle and ETS

1. Lactate (blood or muscle to liver) to pyruvate

2. Pyruvate to glucose (gluconeogenesis)

3. Glucose to glucose-6-phosphate to glucose-1-phosphate

4. converted to LIVER GLYCOGEN with glycogen synthase

1. Glucose from the liver to glucose-6-phosphate

2. to glucose-1-phosphate

3. to MUSCLE GLYCOGEN via glycogen synthase

Glycogenesis = glycogen synthase

Glycogenolysis = glycogen phosphorylase and glucose-6-phosphatase (absent in muscle)

Glucose-6-phosphate

1. Lactate from muscle

2. Transported via blood to liver

3. Gluconeogenesis from lactate in liver

4. Glucose returned to muscle via blood

Plasma glucose: 50-60mg/dl

Energy source: CNS, RBC

Fat synthesis: NADPH, Glycerol

Pregnancy and lactation: Fetal energy, lactose synthesis

Propionate

AA

Lactate

Glycerol

-75-90% of total glucose (occurs at all times)

AA

-plasma glucose 100mg/dl

Muscle lactate from cori cycle

1. Insufficient gluconeogenesis and glycogen stores

- esp. ruminants and neonatal pigs

2.Mesenchymal tumors

-inhibition of glucagon

3.Glycogen storage disease

4.Hyperinsulinemia

-Insulin overdose causing hypoglycemia = increase glucagon and cortisol secretions = HYPERGLYCEMIA and glucosuria

-Organic (tutor of islets) or functional (over secretion of insulin) hyperinsulinism (dogs)

1. Type 1 (juvenile)

-primary insulin deficiency (B-cell failure, autoimmune)

-Dogs and cats

2. Type 2 (adult onset)

-Primary insulin resistance (B-cell exhaustion and atrophy)

-Cats, early lactation cows

3. Gestational Diabetes

4. Diestrus diabetes