Biochemistry - Lecture 21/22 - Digestive System

Front 1

What are the lipid soluble vitamins?

Back 1

D, A, K and E

Front 2

Where are water soluble vitamins found?

Back 2

Most are found in plants except for vitamin b12.
Intrinsic factor formed in parietal cells of stomach are required for uptake of b12.

Front 3

What is pepsin?

Back 3

Protein that functions at low pH in the stomach to break down proteins into polypeptides and amino acids

Front 4

What is Salivary alpha-amylase?

Back 4

Cleaves alpha (1-4) of starch and glycogen to branched oligosaccharides. Functions in the mouth and is inhibited in the intestine because oh low pH.

Front 5

What is Lingual Lipase?

Back 5

Is another enzyme in the mouth which is important in babies and prefer TAGs with medium chained fatty acids.
Majority are palmitate but some medium chained FAs are found in breast milk.

Front 6

What is the function of Gastrin?

Back 6

Is secreted by G cells at the bottom of the gastric gland, and leads to the release of gastric acid from parietal cells into the stomach. Decrease pH - which activates pepsinogen (released by chief cells) to Pepsin .
Pepsin, Lingual lipase and gastric lipase are active.

Front 7

Effect of low pH in the stomach?

Back 7

Denatures protein and DNA and RNA.
Degrades of large proteins and TAGs with medium chain FAs (milk) by lingual and gastric lipase.

Front 8

What is secretin?

Back 8

Released from the duodenum when the stomach chyme enters the duodenum. Secretin acts on the pancreas to activate secretion of water and bicarboante - neutralizing the pH.
Pancreatic enzymes want higher pH in duodenum (Typsin)

Front 9

What causes release of cholecystokinin (CCK)?

Back 9

Is released from the presence of FA (gastric lypase) and AA (pepsin). CCK causes the gall bladder to release bile acids. CCK also acts on the pancreas to release enzyme.
Inhibits gastric motility, stops release of more chyme so it has time to digest.
-Activates enteropeptidase in the duodenum

Front 10

Function of liver in production of bile?

Back 10

Liver cleaves cholesterol to make free cholesterol and puts it into bile salts and phosphatidycholine, and conjugated bilirubin. Addition of bile salts with cholesterol increases solubility to 100,000 fold.

Front 11

What is is pancreatic alpha-amylase?

Back 11

Does not need to be in inactive form. Carbohydrates enzyme do not require zymogen. It is an enzyme that acts on oligosaccharides to form disaccharides sucrose, lactose, maltose and isomaltose.

Front 12

What is the function of pancreatic nucleases?

Back 12

They digest RNA and DNA to oligonucleotides, nucleosides, free bases, ribose and deoxyribose.
Purine free base in excess is bad.

Front 13

Which enzymes from the pancreas must be synthesizes as inactive proenzymes?

Back 13

Protease and phospholipase A2 (PLA). Activated by enteropeptidase which was synthesized by the duodenum and activated by CCK.

Front 14

Enteropeptidase

Back 14

Released into the lumen after action of CCK and is highly specific and only activates trypsinogen.

Front 15

What is Trypsin, what does it cleave and what residues do those enzymes act upon on AA chain?

Back 15

Cleaves at carboxyl of AA at the Arg and Lys residues.
Trypsin cleaves and activates:
Trypsinogen - trypsin
Chymotrypsinogen - chymotrypsin ( Trp, Tyr, Phe, Met, Leu)
Proelastase - elastase (Ala, Gly, Ser)
Procarboxypeptiades - Carboxy Peptidases (Ala, lle, Leu, Val)
Lipid Digest"
Procolipase
Phospholipase A2
Will eventually degrade themselves. End up taking up more proteins than you consumed.

Front 16

What is the function of the trypsin inhibitor protein?

Back 16

Pancreas produces an inhibitor protein that is in the pancreatic juice and inhibits Trypsin if it happens to get activated in the pancreas. Once in intestine, protein is cleaved.

Front 17

Causes of pancreatitis on digestion, what causes it and what are the serum markers?

Back 17

Trypsin make be abnormally active which may activate pancreatic zymogens and destroys pancreas and duct.
Can be caused by gallstones (ALP) or tumors.
Hypertriacylglycerolemia (elevated lipoprotein with high % of TAG)
And from ethanol abuse
Serum markers are alpha-amylase and lipase.
Cholelithiasis - block duct

Front 18

What are some causes of pancreatitis?

Back 18

Can results from blockage of the pancreatic duct from gallstones or Hypertriacylglycerolemia (elevated lipoproteins with high % of TAG) and ethanol.
To test or pancreatitis, look for serum marker alpha-amylae and lipase.

Front 19

What is cholelithiasis?

Back 19

Is cholesterol gallstone disease. Can block pancreatic duct.
Im balance of either too little bile salts and phosphatidylcholine and high cholesterol.

Front 20

What is the function of bile salts?

Back 20

Bile salts in the bile duct emulsify cholesterol.
95% of bile salts are recycled via the enterohepatic circulation.
Formed by conjugation of bile acids with glycine or taurine.

Front 21

What are the characteristics of bile acids that allow it to emulsify lipids?

Back 21

Cholic acid is the primarily bile acid that is synthesized and has one side that is hydrophobic and hydrophilic. Because the pKa of cholic (pKa6) you want bile acids to be conjugated to a charge so it can be more powerful.

Front 22

Function of conjugation by liver and how does lower pKa affect the function of bile acids?

Back 22

Liver conjugated cholic acid (bile acid) with glycine - to glycocholic. It changes pKa to 4.
Also conjugated chenodeoxycholic acid with taurine - to taurochenodeoxycholic - changing pKa to 2.
This leads to negativiely charged molecules at the pH in the lumen of duodenum - helps emulsify cholesterol.

Front 23

What are functions of bile salts?

Back 23

They transport free cholesterol.
Emulsify dietary cholesterol for digestion.
Uptake products of lipid digestion into intestinal mucosal cells.

Front 24

What is the function of pancreatic phospholipase A2?

Back 24

Phosphatidycholine (from bile salt) and phospholipids are cleaved by phospholipase A2 - cleaving acyl group. Product is lysophosphatidycholine and other lysophospholipids + FA (which has detergent character).

Front 25

What is the function of pancreatic lipase and procolipase?

Back 25

Secreted together with procolipase by the pancreas and reaches the intestine. Digestion of dietary TAGs by this enzyme require emulsifcation of lipids by the conjugated bile salts and lyso-phophatidycholine.
Procoplipase is needed to anchor lipase to lipid droplet. And is involved in moving some of the bile salts out of the way.

Front 26

What are the digestive products of prancreatic lipase?

Back 26

Cleaves 2 fatty acids to make 2-monoacylglycerol. This allow it to enter the intestinal mucosal cells.
Also cleaves cholesteryl ester are hydrolyzed which produces cholesterol + FA.

Front 27

Why do we need mixed micelles?

Back 27

These are disk-shaped cluster of amphipathic lipids that coalesce with their hydrophobic groups on inside and hydrophilic groups on outside. They consists of FA, free cholesterol and 2-monoacylglycerol plus bile salts.
Therefore, they are soluble in aqueous environment of the lumen.

Front 28

What is the function of intestinal flora (bacteria) on bile salts.

Back 28

The liver produces primary bile acids which are first conjugated with glycine or taurine to produce primary bile salts. These are transported to the duodenum and are cleaved of their glycine and taurine residues to primary bile acids - which eventually return back to the liver. Bacteria is involved in removing some of these residues but also in converting some of the primary bile acids into "secondary" bile acids.

Front 29

Where are primary and secondary bile acids formed?

Back 29

Primary bile acids are formed in the liver which uses free cholesterol. Secondary bile acids are formed from primary bile acids by intestinal bacteria. Both are conjugated only in the liver

Front 30

What are the assembly and secretion steps of chylomicrons?

Back 30

Fatty acids are converted into their activated form and 2-monoacylglycerols are converted to TAgs by the MAG pathway and uses two fatty acyl CoAs.
These will aggregate in an aqueous environments so they are packaged into a lipid droplet surrounded by phospholipids. This increases solubility for fat-soluble vitamins and cholesterol ester. They chylomicrons are released into the lymph which later join the blood. The TAGs will be cleaved and chylomicron remnants with cholesterol esters and lipid vitamins are taken up by the liver.

Front 31

What enzymes are responsible for the digestion of oligo-and disaccharides digestion of Sucrose, Lactose, and Maltose?

Back 31

Sucrase: sucrose --> glucose + fructose
Lactase: lactose ---> glucose + galactose
Maltase glucoamylase: maltose --> glucose
All of these enzymes are at the brush border of the intestinal lumen.

Front 32

What is congenital lactase deficiency?

Back 32

Autosomal recessive disorder in the deficiency of the enzyme lactase. Inability to break down lactase results in bacteria acting on lactose in the large intestine to produce CO2, H2, and methane. This results in bloating diarrhea and dehydration. In infants this can be life threatening and require special formula without lactose.

Front 33

What is primary lactose intolerance?

Back 33

Activity of lactase is highest in infants and declines by 90% at the age of 7 years in majority of humans. This is very common in Asian and African populations.

Front 34

Secondary Lactose Intolerance

Back 34

Experienced due to damage or loss of intestinal mucosal cells (food poisoning). Results in severe diarrhea or gastroenteritis due to rotavirus.
Also can occur during celiac disease which is immune-mediated damage in response to gluten.

Front 35

How are glucose and galactose taken up into the intestinal mucosal cells?

Back 35

They are taken up via secondary transport of SGLT.
Secondary-ion glucose trasport proteins use the Na+ gradient to transport 1 glucose and 2 Na+ into the cell

Front 36

How is fructose take up into the intestinal mucosal cell?

Back 36

Fructose is taken up via facilitated transport with GLUT-5. Which is a low affinity transporter and also transports glucose at very high concentrations.

Front 37

How are AA taken up into the intestinal mucosal cells?

Back 37

AA are taken up via secondary transport with group specific proteins. Most are sodium dependent co-transporters

Front 38

What is steatorrhea (fatty feces)

Back 38

Could be due to lack of conjugated bile salts
- due to liver damange, liver cirrhosis or bile duct obstruction by gallstones
Defects related to pancreatic juice
-deficiency of enzymes, lack of transport of enzymes or lack of bicarbonate, impair pH
Defective mucosal cells

Front 39

What is CF? What is the cause and what are symptoms?

Back 39

Cystic fibrosis is a deficiency of CFTR. CFTR is an ABC- transporter that opens after phosphorylation by protein kinase A (cAMP) and chloride ions diffuse into extracellular.
Meconium ileus is feces of newborn. We need water to make feces more fluid.
Lack of Cl leads to thick mucus in the lung and pancreatic duct. Dried mucus blocks the pancreatic duct. Dry mucus in lung attracts bacteria. The pancreas can be damaged by fibrosis.