Lecture 12/13 Flashcards

1
Q

What are the 4 major sites of absorption for nutrients in the GI tract?

A
  1. Macro nutrients such as carbohydrates, proteins, and lipids are absorbed in the small intestine, with highest absorption in the duodenum and jejenum
  2. Iron and folate are absorbed in the duodenum, and calcium is absorbed throughout the small intestine
  3. Net absorption of bile acids mainly occurs in the distal jejunum, ileum, and ascending colon
  4. Cobalamin (vitamin B12) is absorbed in the ileum

Slide 4

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2
Q

What are the 6 enzymes used in digestion of carbohydrates?

A
  1. Amylase- reduce polysaccharides for oligosaccharides and brush border enzymes complete the digestion into monosaccharides
  2. Lactase- digests lactose
  3. Maltase, sucrase, isomaltase- xan digest α1-4 linkages of maltose, maltotriose, and α-limit dextrins
  4. Maltase- digests straight chain oligosaccharides 9 monomers long
  5. Sucrase- digests sucrose
  6. Isomaltase- only enzyme to digest α1-6 linkages and α-limit dextrins

Slide 6

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3
Q

What are the 3 channels that mediate carbohydrate absorption?

A
  1. Sodium/glucose cotransporter (SGLT1) mediates absorption of glucose & galactose on the apical surface
  2. Glut5 mediated absorption of fructose on the apical surface
  3. GLUT2 mediated the transport of monosaccharides to the bloodstream on the basolateral side

Slide 6

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4
Q

What is lactose intolerance?

A

Caused by lactose deficiency
Occurs naturally after weaning in many mammals, including some humans
When occurs, consumption of lactose (milk) will commonly lead to diarrhea and increased flatulence
Hydrogen gas can be observed in the breath of lactase deficient person who recently drank milk

Treatment- eliminate lactose from diet

Slide 7

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5
Q

What is glucose-galactose malabsorption?

A

Caused by SGLT1 deficiency
Can lead to diarrhea whenever they consume sugar or lactose

Treatment- eliminate lactose, glucose & galactose from the diet and consume only fructose as a source of carbohydrate

Slide 7

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6
Q

How are proteins digested?

2 ways

A
  1. Gastric (pepsin) and pancreatic proteases (trypsin) reduce proteins into oligopeptides, and in some cases into amino acids
  2. Brush border proteases have a high affinity for 3-8 amino acid length oligopeptides and digest these into smaller peptides and amino acids

Slide 8

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7
Q

How are proteins absorbed?

3 ways

A
  1. Amino acids in the intestinal lumen are absorbed by sodium/amino acid contransporter, 7 types of transporters that sever different types of amino acids
  2. Tetrapeptide, tripeptides, and dipeptides are absorbed by a H/oligopeptides contransporter james PepT1
  3. Transport of amino acids at the basolateral surface from the cytoplasm into the bloodstream is mediated by at least 3 different types of sodium in dependant transporters

Slide 8
Slide 10

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8
Q

What is the kinetic advantage of absorbing oligopeptides, as opposed to single amino acids?

A

It is thought that the reason an oligopeptide absorption mechanism exists is for a higher efficiency in absorption
Evidence for higher efficiency is shown

Slide 9

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9
Q

What is hartnup disease?
What is cystinuria?
What is lysinuric protein intolerance?

A

Hartnup disease- absorption of neutral amino acids is defective, can result in mental disorders

Cystinuria- absorption of cationic amino acids is defective, can result in kidney stones

Lysinuric protein intolerance- impaired basolateral transport of cationic amino acids

Slide 11

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10
Q

How are lipids digested?

A

Dietary lipid is an essential component of the human diet
This is the only source of polyunsaturated fats
Certain vitamins can only be absorbed in fats
Majority of ingested lipid is triacylglycerols with varying degrees of saturated and unsaturated fatty acid composition, small but significant portion will be phospholipids, cholesterol, and cholesterol ethers

Slide 12-13

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11
Q

How are lipids absorbed?

A

Lipolytic products must still cross the mucous later lining the intestine and the apical membrane before they can be absorbed by enterocytes
Mixed micelles are thought to be able to diffuse through the mucous layer and interact with the apical surface of cells
Fatty acids are thought to be neutral at the microvilli surface, and that this helps with cellular uptake
If bile acids are absorbed they are secreted back into the lumen by the ABCG1/ABCG8 transporter to contribute furthermore to mixed micelles formation

Slide 14-15

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12
Q

What is the digestion/absorption of folate?

A

Dietary folate is essential to produce tetrahydrofolate, which is involved in the synthesis of DNA
Folate deficiency can lead to metablastic anemia, and defects in a developing fetus
Foods such as spinach, beans, and liver supply is with this nutrient in the form of folate polyglutamate
To absorb folate, PteGlu7 is deconjugated by a brush border enzyme (folate conjugase)
Once inside the cell, it is converted to the active form of tetrahydrofolate, which is transported into the bloodstream through an unknown mechanism

Slide 16

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13
Q

What is the digestion/absorption of cobalamin?

A

Dietary cobalamin can be found in meat, fish, shellfish, eggs
Critical for DNA synthesis
It is bound to haptocorrin in stomach
Must bind to intrinsic factor for absorption, this occurs in intestine because proteases digest haptocorrin
Intrinsic factor carries cobalamin into enterocytes through receptor mediated uptake
Then transferred to transcobalamin which carries it to bloodstream

Slide 17

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14
Q

How is calcium absorbed?

A

Numerous cellular processes and the formation of healthy bone depends on calcium
The absorption of calcium can occur through paracellular passive uptake in the small intestine
Can also occur through a transcellular active transport mechanism (regulated by vitamin D)
Vitamin D stimulates the uptake of calcium via the TRPV6 calcium channel down its electrochemical gradient, as well as the production of calbindin, and production of a calcium pump and sodium/calcium exchanger

Slide 18

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15
Q

What is the absorption of iron?

A

Iron Is also critical for numerous cellular processes and must be carefully balanced as too much causes hemochromatosis and too little causes anemia
Iron absorption comes from heme and non heme sources

Slide 19

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16
Q

How is non heme iron absorbed?

A

Non heme iron can be ferric or ferrous
Ferrous iron is more soluble at the pH found in the intestine
Ferric iron is converted to ferrous iron by ferric reductase Dcytb, and then ferrous iron is absorbed via the divalent metal co transporter DMT1
Mobilferrin binds ferrous iron and takes it to ferroportin for transport across the basolateral membrane

Slide 19

17
Q

How is heme iron absorbed?

A

Heme bound iron enters enterocytes by an unknown mechanism
In the cell, heme oxygenase will split heme to release ferrous iron, which then travels the same path as described above

Slide 19

18
Q

What is the problem with the certain minerals and inorganic chemicals used to support homeostasis?

A

The cellular processes that support systemic homeostasis require a continued and reliable availability of certain minerals and inorganic chemicals that are essential for a variety of functions
These same agents can be fatal in excess though

Need to maintain a stable level & availability of calcium & phosphate

19
Q

What is calcium’s role in homeostasis?

A

Ca modulates hormone secretion, muscle contraction, nerve conduction, exocytosis, activity of many metabolic enzymes
Needs free Ca levels for all these activity’s, tightly constrained in the bloodstream

Rising levels of free calcium inhibits PTH synthesis and secretion (negative feedback look since PTH increases Ca

Slide 5 lecture 13

20
Q

What is phosphates (PO4-) role in homeostasis?

A

PO4- is key component of ATP, this necessary for the human body to generate the energy currency that is required to support virtually all life processes

21
Q

What are the homeostatic control of calcium and phosphate linked?

A
  1. Together they are the principal components of hydroxyapatite crystals, which is the mineralized portion that gives rigidity to the bones
  2. They are regulated by the same hormones, which are parathyroid hormone (PTH) and vitamin D
22
Q

What is the calcium distribution and balance?

A

Circulating Ca is in one of 3 states:
Free ion (45%)
Protein (albumin) bound (45%)
Complexed with an anion (10%)

Free Ca2+ is tightly constrained at 1.0-1.3mM which is critical for regulating many types of biological processes
Constant and controlled flux of Ca from gut, bone & kidney maintain a net balance

Slide 4 lecture 13

23
Q

What is phosphate (PO4-) distribution and balance?

A

Circulating levels of free PO4 is less tightly controlled and can range from 0.8-1.5 mM
Like Ca, only a small amount of PO4 is in the extracellular fluid as most is in tissues (especially bone)
Constant and controlled flux of PO4 from gut, bone & kidney maintain a net balance

Slide 4 lecture 13

24
Q

What is parathyroid hormone (PTH)?

A

Peptide hormones synthesized and stored in parathyroid glands
Humans have 4 parathyroid glands that are largely made of chief cells which synthesize and secrete PTH
These glands are located on the left and right lobes of the thyroid gland
PTH promotes Ca reabsorption and inhibits PO4 reabsorption in the kidneys
Persistently elevated PTH levels promote bone reabsorption

PTH increases Ca and decreases PO4 levels in circulation

Slide 5 lecture 13

25
Q

What is vitamin D (D3 & D2)?

A

Steroid based vitamin
Vitamin D3- 7-dehydrocholesterol is made via cholesterol synthesis and makes vitamin D3 when reacting with UV light
Vitamin D3 hydroxylated in the liver to 25OH Vitamin D3
Normally large pool of vitamin D in adipose, which takes years to deplete (vitamin D deficiency is rare
When circulating vitamin D is low, adipose releases it

Slide 6 lecture 13

26
Q

What are the actions of vitamin D?

A

Circulated through the blood, bound to proteins it in chylomicrons, then enters a cell and binds to a nuclear receptor (like a steroid hormone) to regulate transcription
Can suppress PTH production, negative feedback loop
In small intestine, vitamin D increases Ca and PO4 absorption
In kidney, it synergizes with PTH to enhance Ca reabsorption

Slide 6 lecture 13

27
Q

What are the 3 homeostatic feedback responses to Ca ingestion?

A
  1. When eating mean with Ca, rise in circulating Ca inhibits PTH which reduces bone reabsorption, which limits post prandial rise in circulating Ca and PO4 and reduces Ca reabsorption in kidneys
  2. If dietary intake keeps circulating Ca levels high, the sustained drop in PTH lowers vitamin D production, which will cause a reduction in Ca absorption in the GI tract
  3. If dietary Ca intake is deficient, circulating Ca levels drop and PTH secretion rises to increase bone reabsorption, Ca reabsorption in kidneys, and vitamin D production

Slide 7 lecture 13

28
Q

What are the 7 Ca linked homeostatic feedback responses to PO4- ingestion?

A
  1. If ingest too much PO4, leads to bone mineralization and lower Ca
  2. This leads to rise in PTH levels causing PO4 excretion by kidneys
  3. PTH promotes bone reabsorption and vitamin D production to reestablish homeostatic level of Ca/PO4 ratio
  4. PO4 levels significantly depend on PTH responses to Ca levels
  5. FGF23 is another regulator of PO4 levels which is secreted by osteocytes
  6. High PO4 levels stimulate FGF23 secretion which decreases PO4 absorption in the intestine and reabsorption in the kidneys
  7. Vitamin D can enhance FGF23 levels by directly acting on parathyroid gland to suppress PTH expression

Slide 7 lecture 13