Biochemistry

the branch of science concerned with the chemical and physico-chemical

processes and substances which occur within living organisms.

Definition of biochemistry. 1 : chemistry that deals with the chemical

compounds and processes occurring in organisms. 2 : the chemical
characteristics and reactions of a particular living organism or biological
substance.

Types of Carbohydrates

There are three main types of carbohydrates: starches, sugars and dietary fiber. Starches and
sugars are considered the energy-yielding carbohydrates because they are fully digestible and,
once absorbed, they provide the body with 4 calories of energy per gram of carbohydrate.
Alternatively, fiber is a type of carbohydrate which is not fully digestible because humans lack
the enzymes to break down fibers. As such, fiber is the main carbohydrate which is eliminated
through excretion.

Carbohdyrate Digestion

The two digestible carbohydrates are starches and sugars, and both of these carbohydrates are
digested, or broken down into their most elementary form, along the gastrointestinal tract.
Amylase, an enzyme which breaks apart starches, is found in the mouth and in the small
intestine. Similarly, the three major enzymes which break apart sugars -- sucrase, maltase and
lactase -- are also found in the mouth and in the small intestine. Once these digested starches
and sugars begin to move through the small intestine, they are able to be absorbed.

Carbohydrate Absorption

Once carbohydrates are broken down into their simplest forms, they are quickly absorbed
along the upper and lower parts of the small intestine. Small, finger-like projections, called
villi, absorb the carbohydrates, then they are transferred to the blood stream and carried to
muscles and the liver.

What Are the Steps to

Digestion for Carbohydrates?

Carbohydrate digestion begins in the mouth.

The main function of carbohydrates is to provide your
body with energy to support muscular work, brain
activity, breathing and other important activities.
Carbohydrates are made up of sugars known as
saccharides. Most carbohydrate foods contain many
saccharides linked together, which are known as
polysaccharides. Carbohydrate digestion begins in the
mouth and is complete when the polysaccharides are
broken down into single sugars, or monosaccharides,
which can be absorbed by the body.

Mouth

Carbohydrate digestion begins in the mouth. The salivary

glands in the mouth secrete saliva, which helps to
moisten the food. The food is then chewed while the
salivary glands also release the enzyme salivary amylase,
which begins the process of breaking down the
polysaccharides in the carbohydrate food.

Stomach

After the carbohydrate food is chewed into smaller

pieces and mixed with salivary amylase and other
salivary juices, it is swallowed and passed through the
esophagus. The mixture enters the stomach where it is
known as chyme. There is no further digestion of chyme,
as the stomach produces acid which destroys bacteria in
the food and stops the action of the salivary amylase.

Pancreas and Small Intestine

After being in the stomach, the chyme enters the
beginning portion of the small intestine, or the
duodenum. In response to chyme being in the duodenum,
the pancreas releases the enzyme pancreatic amylase,
which breaks the polysaccharide down into a
disaccharide, a chain of of only two sugars linked
together. The small intestine then produces enzymes
called lactase, sucrase and maltase, which break down
the disaccharides into monosaccharides. The
monosaccharides are single sugars that are then
absorbed in the small intestine.

Large Intestine (Colon)

Carbohydrates that were not digested and absorbed by

the small intestine reach the colon where they are partly
broken down by intestinal bacteria. Fiber, which cannot
be digested like other carbohydrates, is excreted with
feces or partly digested by the intestinal bacteria.

Digestion and Absorption of LIpids

. 1. Digestion andAbsorptionOf Lipids Biochemistry For Medics

http://www.namrata.co/

. 2.LipidsLipids are heterogeneous group of water insoluble organic molecules

that can be extracted from tissues by non polar solvents.Major source of
energy for the bodyAlso provide the hydrophobic barriers that permit
partitioning of aqueous contents of cells and sub cellular structures. Fat
soluble vitamins have regulatory or coenzyme role in the body. Prostaglandins
and steroid hormones play major roles in the control of bodys homeostasis.
Give shape and contour to the body and protect internal organs by providing a
cushioning effect.

. 3.Dietary fat CompositionMore than 95% are triglycerides, the other

areCholesterol,Cholesteryl esters,Phospholipids, andUnesterified fatty
acids.

. 4.Dietary sources of Lipids Animal SourcesDairy products- Meat, butter,

gheeMeat and Fish, Pork, eggs Vegetable SourcesCooking oils- Sun flower
oil, Mustard oil,Ground nut oilFats from other vegetable sources
. 5.Digestion in MouthHydrolysis of triacylglycerols is initiated bylingual and
gastric lipases, which attack the sn-3ester bond forming 1,2-diacylglycerols and
freefatty acids, aiding emulsification.Lingual lipase:Secreted by dorsal
surface of tongueActive at low pH (pH 2.0 7-5)optimum pH 4.0-4.5Ideal
substrate-Short chain TGS.Milk fat contains short chain fatty acids whichare
esterified at -3 position, thus it is the bestsubstrate for lingual
lipaseEnzymatic action continues in stomachShort chain fatty acids,
released are absorbeddirectly from the stomach wall and enter theportal vein.

. 6.Triglyceride degradationTriglycerides are degraded by lipases to form free

fatty acids and glycerol

. 7.Digestion in StomachGastric Lipase- secreted in small quantitiesMore

effective at alkaline p H (Average p H7.8)Requires the presence of Ca+
+Less effective in stomach due to acidic p Hexcept when intestinal contents
areregurgitated in to the gastric lumenNot effective for long chain fatty acids,
mosteffective for short and medium chain fatty acidsMilk, egg yolk and fats
containing short chainfatty acids are suitable substrates for its action

. 8.Role of fats in gastricemptying Fats delay the rate of emptying of

stomach Action is brought about by secretion of Enterogastrone
Enterogastrone inhibits gastric motility and retards the discharge of bolus of
food from the stomach. Thus fats have a high satiety value.

. 9.Significance of Lingual andGastric Lipases Play important role in lipid

digestion in neonates since milk is the main source of energy Important
digestive enzymes in pancreatic insufficiency such as Cystic fibrosis or other
pancreatic disorders Lingual and gastric lipases can degrade triglycerides
with short and medium chain fatty acids in patients with pancreatic disorders
despite a near or complete absence of pancreatic lipase

. 10.Emulsification and digestion Lipids are hydrophobic, and thus are poorly
soluble in the aqueous environment of the digestive tract. The digestive
enzyme, lipase, is water soluble and can only work at the surface of fat
globules. Digestion is greatly aided by emulsification, the breaking up of fat
globules into much smaller emulsion droplets.

. 11.Emulsification and digestion Triacylglycerol digestion occurs atlipid-water

interfaces Rate of TAG digestion depends onsurface area of this interface
which isincreased by churning peristalticmovements of the intestine
,combined with the emulsifying actionof bile saltsThe critical process of
emulsificationtakes place in the duodenum.

. 12.Digestion in small intestineMajor site of fat digestion Effective

digestion due to the presenceof Pancreatic lipase and bile salts. Bile salts
act as effective emulsifyingagents for fats Secretion of pancreatic juice
isstimulated by- Passage of acid gastric contents in to theduodenumBy
secretion of Secretin, Cholecystokininand Pancreozymin, the gastro
intestinalhormones

. 13.Gastro Intestinal hormones Secretin- Increases the secretion of

electrolytes and fluid components of pancreatic juice Pancreozymin of CCK -PZ
 stimulates the secretion of the pancreatic enzymes Cholecystokinin of CCK-PZ-
causes the contraction of the gall bladder and discharges the bile in to the
duodenum. Hepatocrinin- Released by intestinal mucosa, stimulates more bile
formation which is relatively poor in bile acid content

. 14.Contents of Pancreatic JuicePancreatic Lipase- For the digestion

oftriglycerides Phospholipase A2- for the digestion
ofPhospholipidsCholesterol esterase-For the digestion ofCholesteryl esters

. 15.Bile SaltsBile salts are required for the properfunctioning of the

pancreatic lipaseenzymeBile salts help in combination of lipasewith two
molecules of a small proteincalled as Colipase. This combinationenhances the
lipase activity. Bile salts also help in the emulsificationof fats TG particle
Colipase lipase

. 16.Bile SaltsBile salts are synthesized in the liver and stored in the gall
bladder They are derivatives of cholesterol They consist of a sterol ring
structure with a side chain to which a molecule of glycine or Taurine is
covalently attached by an amide linkage

. 17.Bile SaltsBile salts are formed from bile acidsThe primary bile acids are
cholicacid (found in the largest amount) andchenodeoxycholic acid .The
primary bile acids enter the bileas glycine or taurine conjugates.In the
alkaline bile, the bile acidsand their conjugates are assumed tobe in a salt form
hence the term"bile salts.

. 18.Synthesis of bile saltsIn humans, the ratio of the glycine to the

taurineconjugates is normally 3:1.

. 19.Bile Salts A portion of the primary bile acids in the intestine is subjected
to further changes by the activity of the intestinal bacteria. These include
deconjugation and 7-alpha dehydroxylation, which produce the secondary bile
acids, deoxycholic acid and lithocholic acid.

. 20.Enterohepatic circulation ofBile saltsThe bile salts present in the body are
not sufficient to fullyprocess the fats in a typical meal, thus they need to
berecycled.This is achieved by the enterohepatic circulation.Specific
transporters in the terminal ileum move bile saltsfrom the lumen of the
digestive tract to the intestinalcapillaries.They are then transported directly to
the liver viathe hepatic portal vein.Hepatocytes take up bile salts from the
blood, and increasethe secretion of bile salts into the bile canaliculi,
smallpassage ways that convey bile into the larger bile ducts. 95% of the bile
that is released to the small intestine isrecycled via the enterohepatic
circulation, while 5% of thebile salts are lost in the feces.

. 21.Enterohepatic circulation ofBile salts

. 22.Emulsification by bile saltsBile salts as emulsifying agents interact with

the dietary lipid particles andthe aqueous duodenal contents, thereby stabilizing
the lipid particles asthey become smaller, and preventing them from coalescing.
. 23.Triacyl glycerol degradationby pancreatic lipase Pancreatic lipase is
specific for the hydrolysis of primary ester linkages(Fatty acids present at
position 1 and 3) It can not hydrolyze the ester linkages of position -2
Digestion of Triglycerides proceeds by removal of a terminal fatty acid to
produce an , diglyceride. The other terminal fatty acid is then removed to
produce mono glyceride.

. 24.Triacyl glycerol degradationby pancreatic lipase

. 25.Triacyl glycerol degradationby pancreatic lipase The last fatty acid is

linked by secondary ester group, hence can not be hydrolyzed by pancreatic
lipase. - Mono acyl glycerol can be converted to - Mono acyl glycerol by
isomerase enzyme and then hydrolyzed by Pancreatic lipase. The primary
product of hydrolysis are - Mono acyl glycerol (78%), - Mono acyl glycerol
(6%) with free fatty acids and glycerol (14%)

. 26.Emulsification and Digestionof Triglycerides

. 27.Significance of PancreaticlipaseThe enzyme is present in

highconcentration in pancreas. Only verysevere pancreatic deficiency such as
cysticfibrosis results in malabsorption of fatsdue to impaired digestion.
Orlistat, an antiobesity drug inhibits ,gastric and pancreatic lipases, there
bydecreasing fat digestion and absorptionresulting in weight loss.

. 28.Cholesteryl ester degradation Dietary cholesterol is mainly present in

the free (Non esterified) form Only 10-15% is present in the esterified form
Cholesteryl esters are hydrolyzed by pancreatic Cholesteryl esterase
(Cholesterol ester Hydrolase) to produce cholesterol and free fatty acid The
enzymatic activity is greatly increased in the presence of bile salts.

. 29.Cholesteryl ester degradation

. 30.Phospholipid degradation The enzyme Phospholipase A 2requires bile

salts for optimum activity. Removes one fatty acid from carbon 2 of
Phospholipid to form lysophospholipid. The remaining fatty acid at position 1
can be removed by lysophospholipase , leaving a glycerylphosphoryl base that
may be excreted in the feces, further degraded or absorbed.

. 31.Phospholipid degradation

. 32.Absorption of Lipids Glycerol, short and medium chain fatty acids (Chain
length less than 14 carbons) are directly absorbed from the intestinal lumen in
to the portal vein and taken to liver for further utilization. Long chain fatty
acids, free cholesterol and - acyl glycerol together with bile salts form mixed
micelles.

. 33.Micelles Micelles are disk shapedclusters of amphipathic lipidsthat

coalesce with theirhydrophobic groups on theinside and their hydrophilicgroups
on the outside ofclusters Mixed micelles are soluble inthe aqueous
environment ofthe intestinal lumen The micelles approach thebrush border
membrane of theenterocytes
. 34.Micelles Micelles constantly break down and re-form, It is the
monoglycerides and fatty acids that are free in solution that are absorbed, NOT
the micelles. Because of their nonpolar nature, monoglycerides and fatty acids
can just diffuse across the plasma membrane of the enterocyte. Some
absorption may be facilitated by specific transport proteins

. 35.Clinical Significance ofCholesterol AbsorptionThe drug ezetimibe blocks

a protein that specifically mediates cholesterol transport across the apical
plasma membrane of enterocytes.Ezetimibe has been shown to be effective
at reducing levels of LDL cholesterol, particularly when combined with a statin,
a drug that inhibits cholesterol synthesis in the liver.However, several clinical
trials have shown that further cholesterol lowering with ezetimibe does not
improve measures of atherosclerotic plaque.Clinical trials are in progress to
determine whether ezetimibe (alone or combined with a statin) is beneficial for
preventing cardiovascular events.

. 36.Resynthesis of Triacyl glyceroland Cholesteryl esters Within the

intestinal epithelium, 1- monoacyglycerols are hydrolyzed to fatty acids and
glycerol and 2-monoacylglycerols are re-acylated to triacylglycerols via the
monoacylglycerol pathway. Lysophospholipids are recycled to form
phospholipids. Cholesterol is re acylated to form Cholesteryl esters Long
chain fatty acids are used for esterification to form TGs, phospholipids and
cholesteyl esters. Short and medium chain fatty acid are released in to the
portal circulation and are carried by serum albumin to liver.

. 37.Formation and Transportation ofChylomicrons

. 38.LipidMalabsorption(Steatorrhea)Lipid malabsorption results in increased

lipidsincluding fat soluble vitamins A,D E and K in thefeces. Cause may be
pancreatic insufficiency, includingcystic fibrosis , chronic diseases of pancreas
orsurgical removal of pancreas Shortened bowel, Celiac diseases, sprue
orcrohns diseaseMay be bile duct obstruction due to gall stones,tumor of
head of pancreas, enlarged lymph nodesetc.Milk and coconut oil are used
therapeuticallysince they contain medium chain fatty acids.

. 39.Secretion of lipids fromenterocytesOnce inside the enterocyte,

monoglycerides and fatty acidsare re-synthesized into TAG.The TAG is
packaged, along with cholesterol and fat solublevitamins, into
chylomicrons.Chylomicrons are lipoproteins, special particles that
aredesigned for the transport of lipids in the circulation.Chylomicrons are
released by exocytosis at the basolateralsurface of the enterocytes. Because
they are particles, they aretoo large to enter typical capillaries.Instead they
enter lacteals, lymphatic capillaries that pokeup into the center of each
villus.Chylomicrons then flow into the circulation via lymphaticvessels.

. 40.Structure of Chylomicron Size: 0.11 m Average composition o TG

(84%) o Cholesterol(2%) o Ester Cholesterol (4%) o Phospholipid (8%) o Apo
lipoproteins (2%)

. 41.Transport and Utilization ofchylomicrons

 . 42.Clinical significance of Chylomicronsynthesis and utilization Defective
synthesis- Due to deficiency of apo-B 48 protein. The triglyceride may
accumulate in intestinal cells. Chyluria- Due to an abnormal connection
between urinary tract and lymphatic drainage system of the intestines, forming
Chylous fistula. Characterized by passage of Milky urine. Chylothorax- There
is an abnormal connection between pleural space and the lymphatic drainage of
small intestine resulting in accumulation of lymph in pleural cavity giving Milky
pleural effusion

. 43.Physiologically important lipasesLipase Site of action Preferred Product(s)

substrateLingual / acid Mouth , stomach TAGS with FFA+DAGstable lipase
medium chain FASPancreatic lipase Small intestine TAGS with long
FFA+2MAG+ co-lipase chain FASIntestinal lipase Small intestine TAGS with
2FFA+glycerolwith bile acids medium chain FASPhospholipase A2 Small
intestine PLs with unsat. Unsat FFA+ bile acids FA at position 2
lysolecithinLipoprotein Capillary walls TAGs in FFA+ glycerollipase insulin (+)
chylomicron or VLDLHormone Adipose cell TAG stored in FFA+ glycerolsensitive
lipase adipose cells

. 44.Summary of lipid digestion andAbsorptionChylomicrons deliver absorbed

TAG to the bodys cells. TAG inchylomicrons and other lipoproteins are
hydrolyzedby lipoprotein lipase, an enzyme that is found in capillaryendothelial
cells. Monoglycerides and fatty acids released fromdigestion of TAG then
diffuse into cells.

Digestion and absorption of proteins

. 1. The proteins subjected to digestion and absorption are obtained from two
sources.1.Exogenous2.Endogenous

. 2.The Fate of Dietary Protein The intake of dietary protein is in the range of
50-100g/day.Digestion and absorption .Maintenance of body protein
stores.Net protein synthesis.Synthesis of non-protein
compoundsOxidative deamination

. 3.PROTEINS in the BODYAmino Acid Pool amino acids that are available
throughout the body (tissues and fluids) for use when needed.Protein
Turnover of the ~ 300 grams of protein synthesized by the body each day, 200
grams are made from recycled amino acids.

. 4.Protein DigestionWhole proteins are not absorbed. Too large to pass

through cell membranes intact. H3N+ H C C O H O R N C C HDigestive
enzymes.Hydrolases R N H C C O H O Break peptide bonds RSecreted as
inactive pre-enzymes. Prevents self-digestion.

. 5.Protein Digestion Initiated in stomach HCl from parietal cells

StomachpH 1.6 to 3.2 Denatures 40, 30, and 20 structures Pepsinogen
 from chief cells Pepsinogen HCl Pepsin Cleaves only when carbonyl group of
the peptide bond is contributed by Aromatic amino acids. Protein leaves
stomach as mix of insoluble protein, soluble protein, peptides and amino acids

. 6.Protein Digestion Small IntestinePancreatic enzymes secreted

Trypsinogen Chymotrypsinogen Procarboxypeptidase Proelastase
Zymogens Collagenase

. 7.The release of pancreatic zymogens is mediated by the secreation of

Cholecystokinin and secretin,two polypeptide hormones of digestive tract.

. 8.Digestion inSmall Intestine Zymogens must be converted to active form

Trypsinogen Enteropeptidase/Trypsin Trypsin Endopeptidase Cleaves on
carbonyl side of Lys & Arg Trypsin Chymotrypsinogen Chymotrypsin
Endopeptidase Cleaves carboxy terminal Phe, Tyr and Trp Trypsin
Procarboxypeptidase Carboxypeptidase Exopeptidase Removes carboxy
terminal residues

. 9.Trypsin InhibitorsSmall proteins or peptidesPresent in plants, organs,

and fluids Soybeans, peas, beans, wheat Pancreas, colostrumBlock
digestion of specific proteinsInactivated by heat

. 10.Protein Digestion Proteins are broken down to Tripeptides

Dipeptides Free amino acids

. 11.Peptide Absorption Form in which the majority of protein is absorbed

More rapid than absorption of free amino acids Active transport Energy
required Metabolized into free amino acids in enterocyte Only free amino
acids absorbed into blood

. 12.Free Amino Acid Absorption Free amino acids Carrier systems

Neutral AA Basic AA Na+ Na+ Acidic AA Imino acids Entrance of
some AA is via active transport Requires energy

. 13.Protein DigestionSmall intestine (brush border) Aminopeptidases

Cleave at N-terminal AA Dipeptidases Cleave dipeptides into Aas.
(Enterokinase or enteropeptidase) Trypsinogen trypsin Trypsin then
activates all the other enzymes

. 14.In the Enterocytes First cells that can use the amino acids Transport
into portal blood Protein synthesis Digestive enzymes Structure and
growth Energy

. 15.Basolateral MembraneTransport of free amino acids only* Peptides are

hydrolyzed within the enterocyteTransport mainly by diffusion and Groff &
Gropper, 2000 Na-independent carriers *Whole proteins are nutritionally
insignificant...

. 16.Absorption of Intact Proteins Newborns First 24 hours after birth

Immunoglobulins Passive immunity Adults Paracellular routes Tight
junctions between cells Intracellular routes Endocytosis Pinocytosis
 Of little nutritional significance... Affects health (allergies and passive
immunity)

. 17.Abnormalities in the proteindigestion and amino acidabsorption.Defect in

the pancreatic secreation.Cystic fibrosis,incomplete digestion of fat and
protein,results in abnormal appearance of lipids (steatorrhea) and proteins in
feces.Defective carrier system

. 18.HARTNUPS DISEASEInability of itestinal and epithelial cells to absorb

neutral amino acids.Tryptophan absorption is severely effected resulting in
pellagra.CYSTINUREA.