Lecture 37/38 Flashcards
Digestion of Macronutrients: Carbs, Fats and Proteins
1
Q
dietary carbohydrates
A
REVIEW
- monosaccharides: glucose, galactose, fructose
- disaccharides: sucrose, maltose, lactose
- polysaccharides: glycogen, cellulose, amylose, amylopectin
pg 982
2
Q
disaccharide review
A
- sucrose: glucose - α(1,2) - fructose
- lactose: galactose - β(1,4) - glucose
- maltose: glucose - α(1,4) - glucose
- could also have α(1,6) bonds
pg 983
3
Q
polysaccharides review
A
- glycogen: highly branched polymer of glucose -> α(1,4) and α(1,6) linkages (1,4 -> linear bonds, 1,6 -> branches b/n every 8-10 glucose) -> major storage form of glucose in animals
- starch: two forms in plants -> amylose and amylopectin
- amylose: unbranched, α(1,4) glycosidic linkages
- amylopectin: branched, α(1,4) and α(1,6) glycosidic linkages (α(1,6) branches b/n every ~20 glucose)
pg 984
4
Q
locations of carb digestion in the GI
A
- mouth, intestinal lumen (duodenum), and mucosal lining of the upper jejunum
- mechanical processing (chewing and peristalsis), saliva, duodenum by pancreatic enzymes, intestinal brush border enzymes
- Enzyme: glycosidase -> hydrolase -> uses H2O to break glycosidic bonds
pg 985
5
Q
carb digestion in the mouth
A
- done by salivary α-amylase
- role: breaks large insoluble polysaccharides into smaller soluble ones
- specificity: hydrolysis of α(1,4) bonds ONLY
- substrates: any carb with α(1,4) bonds -> starch, glycogen, maltose
- products: short branched and unbranched oligosaccharides (dextrins)
- pH optimum: 7.0 -> inactivated by the acidic pH of the stomach within 20 minutes
pg 986
6
Q
carb digestion in the duodenum
A
- done by pancreatic α-amylase
- role: continues to break down larger carb molecules into smaller soluble ones
- specificity: hydrolysis of α(1,4) bonds ONLY
- substrates: any carb with α(1,4) bonds -> starch, glycogen, maltose and dextrins
- products: short branched and unbranched oligosaccharides (dextrins) and disaccharides
- pH optimum: 7.0
- Clinical Correlation: plasma levels of α-amylase are used as a diagnostic marker for pancreatitis
pg 987
7
Q
sucrase/isomaltase (SI) complex
A
- one protein cleaved into 2 functional subunits with different activities:
- α(1,2) bonds in sucrose (sucrase)
- α(1,6) bonds (branches) in isomaltose (isomaltase)
pg 988
8
Q
maltase-glucoamylase (MGA)
A
- a single protein with 2 enzymatic activities:
- α(1,4) bonds in maltose (maltase)
- α(1,4) bonds in dextrins (glucoamylase)
pg 988
9
Q
lactase
A
- cleaves β(1,4) bonds in lactose (milk sugar)
- it has high expression in infants and gradual decrease with age
pg 989
10
Q
trehalase
A
cleaves α(1,1) bonds in trehalose (a disaccharide in mushrooms and fungi)
pg 989
11
Q
cellulose
A
- unbranched glucose polymer in plants with β(1,4) glycosidic bonds
- humans do NOT have enzymes to hydrolyze these bonds
- important nutrient as component of dietary fiber (softens stool, increases bowel motility, etc)
pg 990
12
Q
absorption of monosaccharides
A
after carbohydrate digestion, monosaccharides enter enterocytes, then leave the enterocytes and enter the bloodstream to be absorbed
pg 992
13
Q
absorption and transport of monosaccharides
A
Glucose and Galactose
- use SGLT-1 (secondary active transporter) to enter the enterocyte
- use GLUT-2 (facilitated diffusion) to leave the enterocyte and enter the blood stream
- SGLT-1-mediated secondary active transport that requires a symport of sodium ions
Fructose
- Na+ independent facilitated transport
- uses GLUT-5 to enter the enterocyte
- uses GLUT-5 and GLUT-2 to leave the enterocyte and enter the blood stream
pg 993
14
Q
glucose transporters: GLUT proteins
A
- GLUT proteins span the plasma membrane
- facilitated diffusion: ATP-independent
- upon glucose binding it changes conformation, which allows transport across the membrane
- tissue specific expression
- specific regulation and affinity
pg 994
15
Q
GLUT-2
A
- found in the liver, kidney, pancreatic β-cell, and serosal surface of intestinal mucosa cells
- high-capacity, low-affinity transporter
- transports o-monosaccharides from enterocyte into bloodstream
pg 994
16
Q
GLUT-5
A
- found in intestinal epithelium and spermatozoa
- FRUCTOSE specific transporter
pg 994
17
Q
alterations in disaccharide degradation: osmotic diarrhea
A
any deficiency (genetic or acquired) in a specific disaccharidase activity of the intestinal mucosa results in:
- passage of undigested carbohydrate into the large intestine
- this osmotically active material causes water to be drawn from the mucosa into the large intestine, causing osmotic diarrhea
- reinforcement by the bacterial fermentation of the remaining carb to two- and three-carbon compounds plus large volumes of CO2 and H2, causing abdominal craps, diarrhea, and bloating
- Diagnosis: oral tolerance tests with the individual disaccharides, measurement of H2 in the breath
pg 995
18
Q
alterations in disaccharide degradation: lactose intolerance
A
due to lactase deficiency
- congenital -> rare
- age-dependent loss of lactase activity starting around age 2 (as we get older, our body is no longer able to digest lactose)
- treatment: avoid milk and lactose-rich foods, use lactase pills
pg 996
19
Q
alterations in disaccharide degradation: sucrase-isomaltase deficiency
A
- intolerance to ingested sucrose
- autosomal recessive with more than 25 different mutations in the SI gene -> homozygosity leads to osmotic diarrhea, mild steatorrhea, irritability, and vomiting after consuming sucrose -> heterozygous carriers often have symptoms including chronic diarrhea, abdominal pain, and bloating
- treatment: dietary restriction of sucrose and enzyme replacement therapy
pg 996
20
Q
alterations in disaccharide degradation: other causes
A
a variety of intestinal diseases, malnutrition, and drugs that injure the mucosa of the small intestine
pg 996
21
Q
dietary lipids
A
- 90% fats and oils (TAGs)
- 10% others -> cholesterol (animals only) and phospholipids (plants + animals)
pg 999
22
Q
locations of lipid digestion in the GI
A
- begins in the stomach (limited)
- emulsification occurs at the duodenum
- intestinal brush border
- Enzyme: lipases (hydrolyze lipids)
pg 1000
23
Q
lipid digestion in the mouth and stomach
A
- done by salivary lipase and gastric lipase
- role: act in the stomach to hydrolyze FA from TAG molecules with short or medium chain FA (no more than 12 carbons) -> these FAs are found in milk fat
- limited role in healthy adults
- very important role in infants since milk fat is primary source of calories
- pH optimum -> 4.0-6.0 (relatively acid stable)
pg 1001
24
Q
emulsification (duodenum)
A
- increases the surface area of the hydrophobic lipid droplets to allow the enzymes to access the lipids and act effectively (breaks lipid into smaller molecules)
- accomplished by two complimentary mechanisms: use the detergent properties of the conjugated bile salts and phospholipids in the bile and mechanical mixing due to peristalsis
pg 1003
25
enzymatic hydrolysis by pancreatic enzymes
* triacylglycerols: cleaved by pancreatic lipase which requires a co-lipase
* cholesterol esters: storage form of cholesterol; cleaved by cholesterol esterase into free cholesterol and a fatty acid
* phospholipids: cleaved by phospholipases to release the two fatty acids
* pancreatic secretion of hydrolase is controlled by hormones secreted by enteroendocrine cells found throughout the small intestine
* *primary products*: free fatty acids, 2-monoacylglycerol, cholesterol
## Footnote
pg 1004
26
lipid absorption in the enterocytes of jejunum
* primary products of digestion (free fatty acids, 2-monoacylglycerol, and cholesterol) form a mixed micelle for proper absorption at the brush border
* fat-soluble vitamins (A,D,E,K) also absorbed via this method
* in enterocyte: lipids re-esterified and accumulte in lipoprotein called chylomicron
* chylomicrons go to lymph and then blood to reach peripheral tissues and eventually the liver
* chylomicrons needed because lipids are hydrophobic and insoluble in water (GI tract is water system)
## Footnote
pg 1005-1007
27
products of lipid digestion in the blood
* chylomicrons: TAGs, cholesterol (free, esterified), and phospholipids
* medium and short chain FA (less than 14 C)
* glycerol
## Footnote
pg 1008
28
steatorrhea
excess lipids in the feces due to any disturbances in the digestion and absorption of lipids (can also be impacted by carbs)
Potential Causes:
* small intestinal disease/resection: in patients with short bowel syndrome, bariatric surgery
* small intestinal bacterial overgrowth
* pancreatic exocrine insufficiency: in patients with cystic fibrosis (CF), Schwachman syndrome, or Zollinger-Ellison syndrome
* disorders of bile acid metabolism: inadequate synthesis or secretion of bile acids (indigestion of lipids)
* other causes: inadequate synthesis or defective structure of Apo 48 in chylomicrons
## Footnote
pg 1009
29
locations of protein digestion in the GI
* stomach -> denaturation of protein due to acidic pH
* duodenum lumen
* intestinal brush border
* **enzymes**: exopeptidases (start at ends and work toward middle) and endopeptidases -> both hydrolases
## Footnote
pg 1012
30
protein digestion in the stomach
* by stomach juice: contains hydrochloric acid (HCl, pH 2-3) which helps to aid digestion by denaturing proteins and kill microorganisms
* by enzyme pepsin
## Footnote
pg 1013
31
pepsin
* enteropeptidase -> acid stable
* secreted by chief cells of the stomach as a **zymogen** (inactive precursor, proenzyme) -> *pepsinogen* (pepsin zymogen)
* activation: at the low pH, undergoes *autocatalysis* (self-cleavage) to *produce the active pepsin*
* products: shorter polypeptides and amino acids (AA)
## Footnote
pg 1013
32
protein digestion in the duodenum
* enzymes: pancreatic proteases (trypsin, chymotrypsin, elastase, and carboxypeptidases)
* endo- and exo-peptidases with pH optimum, 6.0-7.0
* secreted by pancreas as zymogens
* activation via different mechanisms
* products: oligopeptides and amino acids (AA)
## Footnote
pg 1014
33
protein digestion and absorption in the jejunum
* enzymes: di- and tri-peptidases, aminopeptidases
* membrane bound enzymes localized to small intestinal cells
* final digestion to AAs (and some di-/tri-peptides)
* within the enterocyte, di-/tri-peptides are hydrolyzed to AAs
* final step is transfer of free AA from intestinal cells into the portal blood
## Footnote
pg 1015
34
absorption and transport of amino acids
* amino acids are majority of products at brush border, but dipeptides and tripeptides are also here
* dipeptides and tripeptides can go to enterocytes, but have to break down into AAs there
* transport from brush border through enterocyte and to capillary is active transport that requires ATP and ion-dependent symport
## Footnote
pg 1016
35
transport of AA into the cells
* mostly active transport systems driven by the hydrolysis of ATP
* some facilitated transport occurs
* at least 8 different transport systems are known that have overlapping specificities for different amino acids
* small intestine and proximal tubule of the kidney have common transport systems for AA uptake
* a defect in any one of these systems results in an inability to absorb particular amino acids into the gut cells and into the kidney tubules
## Footnote
pg 1017
36
small intestine and kidney transport systems
1. specific for basic amino acids
2. specific for zwitterionic AAs (monoamino, monocarboxylic acid amino acids)
3. specific for anionic amino acids (asp, glu)
4. specific for proline, hydroxyproline, and glycine
## Footnote
pg 1017
37
cystinuria
* disorder of the proximal tubule's reabsorption of filtered cysteine and dibasic amino acids (ornithine, arginine, lysine - COAL)
* inability to reabsorb cysteine leads to accumulation and subsequent precipitation of stones of cysteine in the urinary tract
* error of AA transport
## Footnote
pg 1018
38
Hartnup disease
* autosomal-recessive mutations in a *Na+-dependent neutral amino acid co-transporter (tryptophan)*
* affected individuals may develop *pellagra-like symptoms* (photosensitivity, dementia) as a result of tryptophan deficiency
* *tryptophan is a precursor in niacin (B3) synthesis*, so the mutation can result in niacin deficiency
* *alternate routes for tryptophan absorption can partially compensate for the defect*
* *patients usually require dietary niacin supplementation*
## Footnote
pg 1018
39
pellagra
* a deficiency of niacin -> a disease involving the skin, GI tract, and CNS
* symptoms progress through the 3 Ds: dermatitis (photosensitive), diarrhea, and dementia
* if untreated, a fourth D, death, occurs
## Footnote
pg 1019
40
celiac disease
* gluten (protein in wheat, barley, rye) triggers autoimmune reaction that damages intestinal cells and results in malabsorption of nutrients
* symptoms: GI-related issues (severe pain, diarrhea, bloody stools) and others that are consequence of the chronic nutrient malabsorption (short stature, delayed puberty, dental and bone issues, nutritional anemias, neurological and psychiatric disorders, behavioral changes, etc)
* treatment: strict gluten-free diet
## Footnote
pg 1020
41
Kwashiorkor
protein deprivation is relatively greater than the reduction in total calories
* severely decreased synthesis of visceral protein; frequently seen in children after weaning at about one year of age when their diet consists predominantly of carbs
* *symptoms*: stunted growth, skin lesions, anorexia, decreased plasma albumin, **edema**, depigmented hair, enlarged fatty liver (lipids cannot be moved out by their protein)
* **edema** results from the lack of adequate plasma proteins to maintain the distribution of water between blood and tissues -> may mask muscle loss
## Footnote
pg 1021
42
Marasmus
calorie deprivation is relatively greater than the reduction in protein
* usually occurs in children less than 1 year old when breast milk is supplemented with watery gruels of native cereals that are usually deficient in both, protein and calories
* *symptoms*: arrested growth, extreme muscle wasting (emaciation), weakness, anemia
* patients with marasmus do NOT show the edema or changes in plasma proteins observed in kwashiorkor
## Footnote
pg 1021
