Week 2 Flashcards
Average Daily Carb intake
300 - 500 g / Day
Average Daily Protein intake
(essential a.a)
40 - 100 g / Day
Average Daily Fats intake
50 - 100 g / Day
Average Daily Water intake
1.5 - 2 L / Day
3 Phases of Digesgtion
1) Luminal phase
2) Small intestinal phase
3) Intracellular digestion
Digestion in Oral phase
- a-Amylase (starch)
- Lipase (important in infants / pancreas dev.)
Absorption in Oral phase
Lipid-soluble substances
(drugs, nicotine, ethanol)
- Nitroglycerin in case of Angina to bypass liver filtration & quicker
Digestion in Gastric phase
- Pepsinogen (10-15% of protein deg.)
- Gastric Lipase
(chief cells)
Absorption in Gastric phase
Lipid-soluble products
(ethanol, lipophilic drugs: aspirin)
Desquamation
Shedding of Enterocytes every 2-3 days to maintain new cells
(basically the cell-turnover)
The macromolecules in cells are reclaimed by GI
Carbohydrate forms
- Amylopectin (branched)
- Amylose (a-1,4 glycosidic)
- Cellulose (B-1,4 glycosidic)
Which carbohydrate form contributes to Feces?
Cellulose
Due to B-1,4 glycosidic bonds bw glucose that cannot be hydrolyzed
Principal dietary disaccharides
- Sucrose
- Lactose
Principal dietary monosaccharides
- Glucose
- Fructose
Luminal Carb. Digestion
a-Amylase hydrolyzes internal a-1,4 glycosidic bonds resulting in:
- Maltose
- Maltotriose
- a-Dextrins
Brush-border Carb. Digestion
Oligosaccharidases on epithelial apical membrane to break disaccharides to monosaccharides
Lactose digestion
Lactase
= Glucose + Galactose
Sucrose digestion
Sucrase
= Glucose + Fructose
Maltose digestion
Maltase (glucoamylase)
= Glucose (1,4)
a-Dextrin digestion
Isomaltase (a-dextrinase)
= Glucose (1,6)
GLUT5
Fructose transport from Apical membrane, Slow & easily overwhelmed
GLUT2
Transport of all 3 monosaccharides
(glucose, galactose, fructose)
Protein intake from internal sources
50g / Day from Desquamation & Enzymes
What % of proteins is digested in stomach?
10 - 15%
What activates Trypsinogen?
Enteropeptidases
How do di/tripeptides get absorbed?
They use H+ coupled transport
(25% of total)
Lipid digestion enzymes
- Lipases (TG)
- Phospholipase A2 (PL)
- Cholesterol esterase (CE)
What is needed to activate Lipid digestive enzymes?
Colipase
- Requires activation by Trypsin in small intestine
- Attached the lipase to fat droplet
What structure is required to absorb digested lipids?
Micelles (mixed)
also contain Bile acids
Lipid uptake mechanism Luminal
1) Micelle interacts with acidic unstirred layer directly above ep.
2) Hydrophobic molecules dissolve out of micelles.
3) Deprotonated FA become protonated & uncharged
4) Now lipophilic molecules are taken up passively
Lipid uptake mechanism Intracellular
1) Digested lipid molecules in enterocytes converted back to TG
2) TG go to SER & Golgi and packaged into Chylomicrons
3) Lipoproteins taken up by Central Lacteals to enter circulation
Absorption of Bile acids
1) After FA taken up due to acidic unstirred layer, only Bile A. remain
- Active uptake: Terminal Ileum by Na+/Bile acid Symporter (conjugated bile)
- Passive uptake: Duodenum by diffusion (unconjugated bile)
What up-regulates Na absorption? & opposite
Aldosterone for expression of ENaC in distal colon
(inh. by amiloride)
Ca2+ Average Daily intake
1 g / Day
Ca2+ Average Daily Absorption
0.4 g / Day
(mostly duodenum & jejunum)
Mostly passive paracellular
What binds Ca?
Calbindin
What regulates Ca absorption in hypocalcemia?
Calcitriol & Parathyroid H.
Entire Iron pool in Body
4 g
Average Daily Iron loss
1 mg / Day
(~3 mg / Day in Women)
2 forms of Dietary Iron
- Heme (absorbed intact by Enterocytes)
- Non-heme (depends on pH)
Non-heme Iron absorption
- Ferric Fe3+: Not soluble at pH7
- Ferrous Fe2+: Soluble at pH7 absorbed by DMT-1
Fat-Soluble Vitamins
ADEK
Water-Soluble Vitamins
- B: 1, 2, 6, 12
- C
- Niacin
- Biotin
- Folic Acid
How much B12 is needed per day?
2 - 4 micrograms / Day
How are most water-soluble Vitamins Absorbed?
Na coupled transport
Absorption of B12
1) Acidic pH & Pepsin release Cobalamin from dietary proteins
2) Salivary & Gastric glands secrete Haptocorrin (R-protein) binding & protecting B12 from low pH
3) R-protein cleaved by proteases from pancreatic juice, IF (par. cells) binds B12
4) Absorbed by Ileal enterocytes
What binds B12 in blood and where does it go?
Transcobalamin II
To Liver
Location & % of Water absorption
- Small Intestines: Jejunum & Ileum ~80 - 85%
- Colon: ~15 - 20%
Water intake per day
9 L / Day
- 2L ingested
- 7L from GI secretions
Out of total daily water intake where is it absorbed & lost?
- 8.5L in Small intestines
- 0.5L passed onto Colon where 80-90% is absorbed, ~100mL excreted
Where are hormones secreted?
Into the blood except for Testosterone in Testicular ducts
Concentration of Hormones in blood
Micro/Nano/Pico-mol / L
(10^ -6 - 10^ -12)
Technical Model of Negative Feedback
Input, Subtractor = Error signal -> Amplifier, Converter (hormone), Target -> Feedback Signal
Perturbation Effect
1) Regulated parameter thrown off
2) Feedback signal deviates
3) Increased error signal changes Hormone release
4) Hormone restores regulated parameter
Weight of Pituitary gland
0.6 g in Adults
Posterior lobe of Pituitary
Neurohypophysis
- Store & Release of Oxytocin + Vasopressin produced by Hypothalamus (SON, PVN)
Anterior lobe of Pituitary
Adenohypophysis
- Acido/Basophilic cells & Chromophobe cells
- GH, Prolactin, ACTH, TSH, LH, FSH
What cell produces GH
Somatotropic Cell
What cell produces Prolactin
Mammotropic (lactotrope) Cell
Placental Hormones GH/PL family
- Human Chorion Somatomammotropin (HCS)
- Growth Hormone (GH)
Glycoprotein Hormone family Subunits
- a-Subunit: Identical 92AA
- B-Subunit: Different, specific.
Glycoprotein Hormones
- TSH (thyrotropic c.)
- FSH, LH (gonadotropic c.)
FSH effects
- Ovary: Granulosa cells, stimulates development of follicles
- Testis: Sertoli cells, Regulates spermatogenesis
LH effects
- Ovary: Theca cells
- Testis: Leydig cells
Placental Hormones Glycoprotein family
Human Chrionic Gonadotropin (HCG)
- Bids LH-R maintaining corpus lut.
- Basis of pregnancy test
- Peak in first trimester
Pro-opio-melano-cortin Hormone Family (POMC)
- Makes a precursor polypeptide Prohormone
- Needs to be cleaved to form hormones in ant/mid pit.
(ACTH, B-endorphins, a-MSH)
What cell produces ACTH
Corticotropic cell
ACTH effects
- Major effects on Adrenal cortex Fasciculate layer
- F-layer produces glucocorticoids like Cortisol
B-endorphins effects
Opioid
- NT & Hormone associated with Hunger, Sex, …
a-MSH effects
- Skin pigmentation & hair
- First 13 a.a of ACTH
Regulation of Pituitary Hormone secretion
- Hypothalamic Releasing Hormones (RH)
- Hypothalamic Release Inhibiting Hormones (RIH)
- Negative-feedback from target hormones
Portal circulation of Pituitary
1) Capillary bed on Median eminence of Hypothalamus receives RH & RIH
2) Hypophyseal portal veins carry hormones to 2nd capillary bed
3) Adenohypophysis or anterior pituitary receive these RH + RIH hormones
Growth Hormone Releasing Hormone (GHRH)
Stimulates GH
(Gs)
Somatostatin (SST)
Inhibits GH & TSH
(Gi)
Thyrotropin Releasing Hormone (TRH)
Stimulates TSH
(Gq)
Gonadotropin Releasing Hormone (GnRH)
Stimulates LH & FSH
(Gq)
Can be Gi inhibitory for pulsatile flow to prevent desensitization
Corticotropin Releasing Hormone (CRH)
Stimulates ACTH
(Gs)
Vasopressin Parvocellular & CRH
1) High ADH released by parvocellular cells in SON & PVN goes from Median eminence to ant. Pituitary
2) V1B-R (Gq) couples with CRH to release more ACTH
Vasopressin Magnocellular & CRH
1) Lower ADH released by Magnocellular cells in SON & PVN enter systemic circulation through Posterior Pituitary
2) V2-R (Gs) high affinity reg. water reabsorption
Dopamine
D2-R (Gi)
- Inhibition of Prolactin
Inhibitors for GH secretion
- Somatostatin
- Hyperglycemia
- Increased blood FFA
GH Receptor Signaling
Cytokine signaling with Tyrosine Kinase
1) JAK2 activated and STAT5 is phosphorylated
2) STAT5 dimerizes and moves to Nucleus
3) Increased Gene expression
Somatomedins
Local growth factors/hormones stimulated by GH responsible for indirect effects of GH
(IGF-1, NGF, EGF, PDGF, bFGF)
IGF-1 Role
Special Somatomedin (C) that enters blood through Liver and does not only act locally.
- Negative feedback of GH release through Somatostatin release
- Has a binding protein in blood
GH in fasting state
- GH increases to increase blood glucose levels
- Somatomedins do NOT increase as we do not want to grow
- So only primary GH effects are seen
When is GH administered?
- GHRH production issue
- GHRH receptor issue
- GH production issue
When is IGF-1 administered?
- GH receptor issue
- IGF-1 production issue
- IGF-1 receptor issue
