NBA6 Nutrient digestion + absorption + nutrient sensing
21 important questions on NBA6 Nutrient digestion + absorption + nutrient sensing
Mechanisms of water-soluble vitamin absorption; vitamin B12
- release of bound B12 by acid-peptic digestion; binding of B12 to haptocorrin; release of B12 from haptocorrin by pancreatic enzymes; complex with intrinsic factor
Transport
- membrane receptor (cubilin); endocytosis and processing via endosomal-lysosomal pathway;B12 enters transcobalamin-contaning secretory vesicles, transports through Bas-lateral membrane, and binds to transcobalamin II
Vitamin B12 absorption
- Vitamin B12 is released from food
- Vitamin B12 binds to R proteins found in saliva and gastric juice
- Within the small intestine R protein is digested to release vitamin B12
- Vitamin B12 binds intrinsic factor (IF) forming a complex in the small intestine
- The vitamin B12-IF complex binds to a receptor on enterocytes in the ileum and gets internalized by endocytosis
What needs to be known about mineral absorption
- The vast bulk of mineral absorption occurs in the small intestine
- the best-studied mechanism of absorption are for calcium and iron
- for many minerals specific ATPase activity is required
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How is calcium being absorpted?
- Duodenum and jejunum
- two distinct mechanisms:
- active, transcellular absorption
- requires carrier
- passive, paracellular absorption
- only when moderate or high amounts in diet
- stimulated by vitamin D
How is iron absorpted?
- Heme iron (represents ±10-15% of dietary iron intake)
- ±20% absorbed
- present in meats
- absorption not affected by other compounds
- Nonheme iron (±80% dietary intake)
- ±max 2-3% absorbed
- absorption susceptible to inhibition/stimulation by other dietary constituents
Why nutrient sensing?
- To control nutrient/energy intake
- two different levels
- cellular level
- whole intestine
- required: receptors and/or afferent/efferent nerves
- ultimate effect: appetite regulation
The gut endocrine system
where are which cells located
- intestinal stem cells
- paneth cells
- transit amplifying cells
- goblet cells
- enteroendocrine cells
- enterocytes
Enteroendocrine cells, what do they do?
they make gut hormones
- Restricted to mucosa; deeper half; only ±1% of epithelial population
- diversity higher in small intestine than colon
- various subtypes (>12); secrete > 20 hormones
- secreted hormones act locally, on other cells, on nerves ending or other organs
every enteroendocrine cell is different, it has a different specialisation --> so they make different hormones (>12 subtypes and make >20 hormones)
Enteroendocrine cells, what do they do?
they make gut hormones
- Restricted to mucosa; deeper half; only ±1% of epithelial population
- diversity higher in small intestine than colon
- various subtypes (>12); secrete > 20 hormones
- secreted hormones act locally, on other cells, on nerves ending or other organs
every enteroendocrine cell is different, it has a different specialisation --> so they make different hormones (>12 subtypes and make >20 hormones)
What can the gut hormones made by enteroendocrine cells do?
- endocrine - distant target cell
- autocrine
- neurocrine
- paracrine
Effects of the gut hormones are pleiotropic it does the regulation of:
- Appetite and satiety
- changes gastric emptying and intestinal transit
- release of digestive enzymes
- induction of nutrient transporters and digestive enzymes
- increase intestinal barrier function
- modulation of tissue growth and immune response
What are the locations and principal effects of GIP and GLP-1?
- proximal small intestine
- stimulation of insulin release
GLP-1
- distal small intestine, colon
- stimulation of carbohydrate uptake, slowing of intestinal transit, appetite regulation, insulin release
What can be seen in the simplified model of nutrient sensing?
G protien
What is the G protein-coupled receptor structure?
- The extracellular domain contains the binding site for a ligand (a hormone or neurotransmitter)
- seven trans-membrane helices
- intracellular domain that interacts with G proteins
What are the components of the hormone receptor - G protein effector system
no hormon: inactive effector
Bound hormone (H): active effector
N; C; E; H; alfa; beta; gamma; GDP/GTP
Signal amplification by second messengers, how does this work
-->>intracellular effects
Signal amplification by second messengers, how does this work
-->>intracellular effects
What are the surface receptors for
- free fatty acids
- carbohydrates
- peptide and amino acids
- bile acids
- free fatty acids
- FFAR1-3, GPR119, GPR120, ILDR1
- carbohydrates
- T1R2-T1R3, SGLT1
- peptide and amino acids
- CasR, LPAR5, GPR92, GPR93, GPRC6a, T1R1-T1R3
- bile acids
- TGR5
an enteroendocrine cell expresses multiple receptors
What are the functional impacts (g protein)
- Modulating digestive tract motility
- e.g. Serotonin
- Food perception and feeding behaviour
- e.g. PYY/GLP1/GIP
- Microbiota monitoring
- e.g. GPR41/GPR43
What are the biological functions of GIP and GLP-1?
- increase bone formation
- increase memory
- increase insuline, beta cell mass, glucagon
- decrease gastric acid secretion
- increase fat accumulation
GLP-1
- increase memory
- decrease food intake
- increase insulin, beta cell mass
- decrease glucagon
- decrease gastric emptying
- increase cardio protection and cardiac output
Stimulation of GIP and GLP-1 secretion
Secretion stimulated after meal ingestion:
- rich in fast and glucose; rate of absorption
- made by
K cells
GLP-1
- rich in fats and carbohydrates, presence in lumen
- made by L cells
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