Absorbsi Makro dan Mikronutr,

Air
Amallia N. Setyawati
Dept of Biochemistry, FMDU
http://staff.undip.ac.id/fk/amallia_setyawati/
 The Odyssey
• The gastrointestinal tract:
– Includes the esophagus, gall bladder, liver,
stomach, pancreas, small intestine, large
intestine, rectum, and anus (which are both part
of the large intestine).
– Its entire length from the mouth to the anus is 6-8
meters long.
– It is the tube that supplies nutrients and water to
the body.

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 The GI Odyssey
– The nutrients are delivered to the liver by way of
the hepatic-portal vein and then they are
distributed throughout the body by the circulatory
system.
– It takes the GI tract 1-3 days to eliminate the
ingested food.

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 Mouth & Esophagus
• By chewing, grinding, mashing and softening food
particles, food becomes easier to swallow and
becomes accessible to enzymes and other digestive
substances that start the breakdown process.
• Smooth muscle contracts rhythmically causing the
contents to move (peristalsis).
• This happens at zero gravity even if a person is
turned upside down.
• At the end of the esophagus is the esophageal
sphincter which is a one way ring of muscle that
relaxes to allow the food to enter the stomach.

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 The Stomach
• The sto a h’s olu e a ra ge fro .5 liters
when empty to up to 6 liters when distended
after an extremely large meal.
• Inside the stomach wall are gastric glands.
These glands secrete hydrochloric acid and
other powerful enzyme containing digestive
juices that continually degrade the nutrients.

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 The Stomach
• Carbohydrates are the easiest
macronutrient to digest and leave the
stomach most rapidly, followed by proteins
than fats.
• It takes between 1-4 hours to empty
depending on the nutrient concentration
and volume of the meal.
• The food mixes with a chemical substance
called chyme, and then passes through the
pyloric sphincter into the small intestine

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 The Small Intestine
• Approximately 90% of digestion (and essentially all
lipid digestion) takes place in the first two sections of
the 3 meter long small intestine.
• It is a coiled structure with three sections called the
duodenum, jejunum and the ileum.
• There are tiny fingerlike protrusions along the walls
of the small intestine called villi.
• These structures absorb the carbohydrates, proteins,
lipids, water, vitamins and minerals.

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 The Small Intestine
• The intestinal walls are made up of smooth muscle
that contract and relax moving the food or chyme
forward then slightly backward.
– This gives the intestine additional time for
absorption.
– Here the pancreas secretes 1.2-1.6 liters of alkali
containing juice to help buffer the hydrochloric
acid that mixes with the chyme and enters into
the small intestine from the stomach.
• Neutralizing this acid is crucial otherwise it causes
ulcerations or ulcers.

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 The Large Intestine
• This is the final digestive structure.
• It consists of the ascending and descending
colon, transverse colon, sigmoid colon, rectum
and anal canal. It is 1.2 meters long.
• By the time the digested food or chyme reaches
the large intestine, most of the nutrients have
been absorbed.
• The primary role of the large intestine is to
convert chyme into feces for excretion.
• Here the colon absorbs water from the chyme,
changing it from liquid to solid. The large
intestine does not contain villi.

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 The Digestive Process
Carbohydrate digestion and absorption
• Carbohydrates start breaking down in the mouth.
• The enzyme salivary amylase starts breaking up
the starches reducing it into smaller glucose
molecules where in the stomach it continues to be
broken down further.
• Upon entering the small intestine the pancreas
releases the enzyme pancreatic amylase to help
complete the hydrolysis of starch into smaller
chains of glucose molecules – monosaccharides,
which is 1 molecule of sugar.

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 The Digestive Process

(Carbohydrate digestion continued)

• The monosaccharides are absorbed into
the small intestine and delivered to the
liver by way of the hepatic portal vein.
• After the liver processes the nutrients, the
nutrients enter into the blood stream
circulating throughout the body.

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 The Digestive Process
Lipid or fat digestion and absorption
• In the stomach fats are broken down into
glycerol and fatty acids.
• The digestion of fats starts in the stomach when
mixed with the enzyme lipase.
• The major part of the breakdown takes place in
the small intestine.
• In the duodenum the enzyme pancreatic lipase
furthers the process by breaking the fats down
from triglycerides to monoglycerides (which is 1
fatty acid instead of 3 fatty acids connected to a
glycerol molecule).

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 The Digestive Process
(Lipid/fat digestion and absorption
continued)
• Bile is produce in the liver and secreted by the
gall bladder which increases the lipids solubility,
breaking it down into droplets, making it easier
for the small intestine to absorb.
• When foods with high lipid content enter the
stomach, the hormone – gastric inhibitory
peptide is released, slowing down movement
flow out of the stomach.
• This is why we feel full after eating high fat foods.

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 The Digestive Process
Protein Digestion and Absorption
• Proteins are split into linked amino acids called
peptides and then into individual amino acids.
• In the stomach the enzyme pepsin starts the
breakdown of proteins into smaller units called
polypeptides and peptides.
• In the duodenum of the small intestine the
pancreatic enzymes trypsin and chymotyrpsin
also split proteins into polypeptides and peptides.

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 The Digestive Process
(Protein Digestion and Absorption continued)
• In the jejunum of the small intestine an enzyme created
by the small intestine called peptidase splits the large
peptides into smaller peptides and than into amino
acids.
• All of these smaller protein fragments go directly to the
liver by the hepatic portal vein.
• Once in the liver one of three things happens to the
proteins:
– 1. It converts to glucose,
– 2. It converts to fat or
– 3. It is directly released into the blood as amino
acids.
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 The Digestive Process
Vitamin Absorption
• Vitamins are absorbed mainly in the jejunum
and ileum sections of the small intestine. A,
D, E, and K are the fat soluble vitamins and
they must be absorbed in combination with
fat.
• Fat is the transport for which the vitamins are
delivered to the liver.

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 The Digestive Process
(Vitamin Absorption Continued)
• The B’s a d C ita i s are ater solu le
vitamins.
• They start breaking down in the stomach and
then throughout the small intestine.
• They do ot re ai i the ody’s tissues ery
long and the excess is passes on into the
urine.

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 The Digestive Process
Mineral Absorption
• Intestinal absorption of minerals increases
when the body is lacking the particular
nutrient.
• Intestinal absorption of minerals decreases
when the body is not lacking the particular
nutrient.

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 The Digestive Process
Water Absorption
• Saliva, gastric secretions, bile, pancreatic acids and
intestinal secretions take up approximately 7 liters of
water, when combined with an intake of an average
of 2 liters of water ingested, the body is processing
approximately 9 liters of water daily.
• 72% is absorbed in the first half of the small
intestine, 20% is absorbed in the lower half of the
small intestine, and 6% is absorbed in the large
intestine.

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NUTRIENT ABSORPTION in the SMALL
INTESTINE
• Most absorption occurs in the SI – 90%
• Provides the surface area equivalent to a
tennis court!
• Nutrients are trapped in folds of the intestinal
wall and absorbed through the microvilli
• Each villus contains blood vessels and a lymph
vessel which transport nutrients
NUTRIENT ABSORPTION in the SMALL
INTESTINE

• Water-soluble nutrients are absorbed

directly into the bloodstream
• Fat-soluble lipid compounds are
absorbed into the lymph rather than
the blood
NUTRIENT ABSORPTION in the SMALL
INTESTINE
• Duodenum and Upper Jejunum: most
minerals (except sodium, chloride, and
potassium)
• Jejunum and Upper Ileum: carbohydrates,
amino acids, water-soluble vitamins
• Jejunum: lipids and fat-soluble vitamins
• Terminal Ileum: Vitamin B12
 LARGE INTESTINE

• Is ~ 5 feet long and includes the

cecum, colon, rectum, and anal canal
 NUTRIENT DIGESTION in the LARGE
INTESTINE
• Little digestion occurs in the large
intestine
• The large population of bacteria digests
small amounts of fiber
• This bacterial activity forms: Vitamin K,
Vitamin B12, Thiamin, Riboflavin, Biotin,
and gases
NUTRIENT ABSORPTION in the LARGE
INTESTINE
• Little absorption occurs in the large
intestine
• However, it does absorb: water,
sodium, potassium, chloride, and
some of the Vitamin K produced by
bacteria
• It does not absorb Vitamin B12
 M1 - GI Sequence

Micronutrients

Winter, 2009
 ESSENTIAL MINERAL ELEMENTS

1. Required to maintain normal physiology and

health

2. Occur in diet, sometimes as trace elements

3. Variable absorptions may be regulated

4. In steady state intestinal absorption equals

body losses
MINERAL ABSORPTION BY SMALL INTESTINE
IS AFFECTED BY:

1. Intraluminal pH

2. Redox state of metals

3. Formation of chelates to enhance solubility

4. Formation of insoluble complexes

 IRON

1. Essential for oxidative energy metabolism

and DNA synthesis

2. Body stores contain about 4 g with 2.5 g in

red blood cells

3. To maintain a balance, the gut absorbs 1-2

mg/day from dietary supply of 10-20 mg
 CELLULAR IRON HOMEOSTASIS

1. All cells take up iron-transferrin from plasma by

transferrin receptor endocytosis.

2. Iron is stored intracellularly complexed to the binding

protein ferritin.

3. Iron regulatory proteins function as cytoplasmic iron

sensors and increase Tf Receptors by stabilizing mRNA
when more iron is needed.

4. Efflux from cells such as macrophages is by ferroportin.

 IRON ABSORPTION
1. Dietary iron present as heme (minor) and
nonheme iron compounds (major).

2. Nonheme iron in the Fe3+ ferric state requires

gastric acid for solubilization.

3. Fe3+ mainly reduced to Fe2+ (ferrous) prior to

absorption.

4. Iron absorption occurs primarily in the

duodenum and upper jejunum.
Model for Absorption of Iron by the Small Intestine

Source Undetermined
Mechanism of Iron Absorption by Enterocytes

Source Undetermined
 NEW PROTEINS INVOLVED IN IRON ABSORPTION

Ferrireductase Apical membrane enzyme to reduce iron

DMT-1 Divalent Metal Transporter-1

Apical Membrane Iron Transport

Ferroportin-1 Iron Export Carrier on the Basolateral

Membrane

Hephaestin Basolateral membrane protein which

facilitates the transport of iron out of cells
Role of Ferritin in the Regulation of Iron Absorption

Fig. 29-16 Rhoades, R, Tanner, G. Medical Physiology. 1995: 568.

 Role of Liver in Regulating Iron Absorption

1. Liver is main storage site for excess iron

2. Hepcidin is an antimicrobial peptide secreted by

hepatocytes which it acts as an inhibitor of iron
absorption by the gut and release from macrophages.

3. Production of hepcidin is decreased by iron deficiency

and increased with iron loading and inflammation

4. Hepacidin interacts directly with ferroportin leading to its

degradation. This leads to decreased iron absorption and
release
ORGANISMAL IRON HOMEOSTASIS

Source Undetermined
CAUSES OF IRON DEFICIENCY

1. Dietary Deficiency

2. Excess phytate or oxylate in diet

3. Gastric achlorhydria

4. Hookworm infestation

5. Excessive bleeding
CONSEQUENCES OF IRON DEFICIENCY

1. Anemia (microcytic, hypochromic)

2. Poor growth in children

3. Impaired energy metabolism

 HEREDITY HEMOCHROMATOSIS
1. Common form is autosomal recessive with
gene frequency as high as 1 in 10 in
individuals of Northern European descent
2. Excessive mucosal iron absorption relative
to need
3. Clinical manifestations are a result of iron
deposition in liver, heart, pancreas and joints
4. >80% of patients have a single mutation in
HFE protein which leads to decreased
plasma hepcidin
 Iron Stain of Liver in Hemochromatosis

Source Undetermined
 ABSORPTION OF VITAMINS

1. Water soluble vitamins

- facilitated diffusion (Na+-coupled)

2. Fat soluble vitamins

-absorbed same as other lipids

3. Vitamin B12
-special receptor
-requires intrinsic factor
 WATER SOLUBLE VITAMINS

Thiamine Pyridoxine Folate

Riboflavin Pantothenate Cobalamin (B12)

Niacin Biotin Ascorbic Acid

Generally metabolized to forms acting as coenzymes

Vit C functions as a water soluble antioxidant

 Structure of Conjugated Folates

Fig. 1 Chang, E, Sitrin, M, Black, D. Gastrointestinal, Hepatobiliary, and Nutritional Physiology. Lippincott – Raven, Philadelphia, PA; 1996: 190.
 FOLATE DEFICIENCY

1. Folates function as coenzymes in 1 carbon

transfers; important in nucleic acid synthesis
and amino acid metabolism
2. Deficiency results in megaloblastic anemia and
growth retardation
3. Recent studies show a relationship to neuronal
tube birth defects
PHS recommends women of childbearing
age
consume 400 μg daily
Metabolism and Absorption of Conjugated Folates

Fig. 2 Chang, E, Sitrin, M, Black, D. Gastrointestinal, Hepatobiliary, and Nutritional Physiology. Lippincott – Raven, Philadelphia, PA; 1996: 191.
Polyglutamyl folates must be hydrolyzed to the monoglutamyl form before
absorption

A specific enzyme, folate conjugase, is involved which is inhibited by ethanol and

some drugs (Dilantin, sulfasalazine)

Absorption is by a saturable mechanism involving a folic acid: OH- exchange

mechanism

Within enterocyte folic acid is reduced and methylated

FAT SOLUBLE VITAMINS

A – Retinol, carotenoids

D – Cholecalciferol (D3); Ergosterol (D2)

E – α-Tocopherol

K – Phylloquinone (K1); Menaquinones (K2)

 VITAMIN E

1. The major lipid soluble antioxidant in plasma

and cell membranes

2. Dietary Sources are vegetable oils, wheat germ,

nuts, green leafy vegetables. Recommended
intake 15 mg/day

3. Absorption varies from 10-80% by passive

diffusion and packaging into chylomicrons

4. Role in therapy unclear (macular degeneration,

cardiovascular disease, prostate cancer)
 VITAMIN K

1. Biological function is to serve as a cofactor

for essential post-translational modifications
essential for certain proteins including blood
clotting factors
2. Dietary form (K1) most abundant in green
leafy vegetables
3. Insoluble in water; requires bile salts for
absorption
4. Importance of bacterially derived K2
controversial but prevents severe deficiency
in humans unless colonic flora absent
 Vitamin A Family

Source Undetermined

Retinoids present in liver, milk, eggs

Carotenoids present in carrots and green leafy vegetables
DISORDERS OF VITAMIN A HOMEOSTATIS
1. Vitamin A deficiency results in xeropthalmia;
initially night blindness can progress to total
blindness
2. Deficiency also increases susceptibility to
infection
3. Recommended daily intake of 1000 μg
retinol or 6000 ug beta carotene
4. Hypervitaminosis most commonly due to
self-medication; can result in signs and
symptoms of increased intracranial pressure,
skin lesions and hepatic injury
Intestinal Absorption and Metabolism of Vit. A

Fig. 3 Chang, E, Sitrin, M, Black, D. Gastrointestinal, Hepatobiliary, and Nutritional Physiology. Lippincott – Raven, Philadelphia, PA;
1996: 166.
Hepatic Vitamin A Metabolism and Storage

Fig. 6 Chang, E, Sitrin, M, Black, D. Gastrointestinal, Hepatobiliary, and Nutritional Physiology. Lippincott – Raven, Philadelphia, PA;
1996: 170.
Uptake, Metabolism and Action of Retinol and Retinoic Acid

ROL = Retinol RA = Retinoic Acid

RBP = Serum Retinol Binding Protein
CRABP = Cellular Retinol Binding Protein
RXR = Retinoid X Receptor
RAR = Retinoic Acid Receptor
Fig. 7 Chang, E, Sitrin, M, Black, D. Gastrointestinal, Hepatobiliary, and Nutritional Physiology. Lippincott – Raven, Philadelphia, PA; 1996: 171.
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