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Summary BBS2041 - Human Intermediary Metabolism
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Summary BBS2041 - Human Intermediary Metabolism
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BBS2041 – Jits Korsten i6275941Anatomy GI tract
General structure and layers of GI tract:
- Mucosa epithelium with connective tissue, containing
blood/lymph vessels, smooth muscle, lymphocytes and
lymphoid nodules.
- Submucosa connective tissue with large vessels, submucosal nerve plexus and glands.
- Muscular layer circular/longitudinal smooth muscle, between myenteric nerve plexus.
- Serosa mesothelium, also called adventitia.
Organs of GI tract
Mouth stratified squamous epithelium. Keratinized on gums, hard plate, and dorsum of tongue.
Esophagus stratified epithelium, joins stomach in cardiac orifice, surrounded by gastroesophageal
and cardiac sphincter. Mucous cells on both sides of sphincter for protection of acid.
Stomach upper left quadrant of peritoneal cavity, nearly hidden by liver and diaphragm. Contains
gastric pits that lead into tubular gastric glands that produce gastric juice.
- Cardia surrounds cardial orifice through which
food enters stomach.
- Fundus stomach dome-shaped part, used for gas.
- Body midportion of stomach, containing lesser-
and greater curvature.
- Pyloric antrum narrows from the pyloric canal.
- Pylorus gate at end of stomach.
Gland cells in stomach:
- Mucous neck cells produce soluble mucus.
- Parietal cells secrete hydrochloric acid and intrinsic
factor.
- Chief cells produce pepsinogen, which is activated by HCl.
- Enteroendocrine cells release chemical messengers into
interstitial fluid of lamina propria.
Small intestine high adapted for absorbing nutrients. Has circular
folds, villi, and microvilli – amplifying absorptive surface by a factor
more than 600 times. Three subdivisions:
- Duodenum 25cm, containing bile duct
- Jejunum 2,5m
- Ileum 3,6m
Large intestine different parts:
- Cecum
- Appendix, masses of lymphoid tissue, important in immunity
- Ascending, transverse, and descending colon.
- Rectum.
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Macronutrients
Carbohydrates
Provide energy for muscle and CNS during movement and exercise. Broken down into glucose, or
sugar molecules. Functions: (1) instant energy, (2) energy store (glycogen in muscle and liver), and (3)
digestion.
Breakdown
Carbohydrates are derived from sugars and starches. Sugar include monosaccharides (glucose,
galactose, and fructose) and disaccharides (lactose, sucrose, maltose, and trehalose).
Monosaccharides are absorbed in the small intestine.
- Lactose and sucrose are hydrolyzed to monosaccharides by lactase and sucrase.
- Salivary and pancreatic amylases are responsible for the initial breaking down of starches,
followed by further digestion by mucosal enzymes (amylase, sucrase, isomaltase) which are
responsible for the final digestion to glucose.
- Fructose is transported across the brush border via GLUT5. And is transported across the
basolateral membrane via GLUT2.
The SGLT1 transporter on brush border of
enterocytes is a Na+-dependent transporter for
glucose and galactose. The Na+ gradient is
maintained through the basolateral Na +/K+
ATPase pump. Two Na+ ions accompany each
sugar molecule into the cells.
Proteins
Involved in metabolic, hormonal and enzyme systems and help maintain acid-base balance. Digested
into amino acids. Functions: (1) build and repair, (2) providing structure, (3) pH balance, and (4)
creating enzymes and hormones. Structure:
- Primary sequence of amino acids, polypeptide chain.
- Secondary chain folded into alpha helix or beta sheet.
- Tertiary 3D structure due to bond between amino acids.
- Quaternary multi polypeptide chains combine.
Essential amino acids cannot be synthesized by body.
- Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and
valine.
Non-essential amino acids synthesized by body due to breakdown of other proteins.
- Alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine,
proline, serine, and tyrosine.
Breakdown
Peptide bonds of proteins are cleaved by pepsin, which is the activated form of pepsinogen. The
peptide bonds are further broken down into amino acids, dipeptides, and tripeptides by pancreatic
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enzymes (trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidase) that are activated by
mucosal enterokinase.
Sodium creates a gradient for hydrogen needed for peptide co-transport.
Dipeptides and tripeptides are indirectly absorbed in a Na +-dependent manner. Peptides of four or
more amino acids in length are absorbed in a non-carrier-dependent mechanism. The carrier
responsible for intestinal uptake of peptides is peptide transporter 1 (PEPT1), expressed throughout
the small intestine and has a high capacity of transport.
Amino acids exit through the basolateral membrane of the enterocyte via at least six amino acid
transporters.
- Endopeptidase breaks peptide bonds in interior of amino acid chain. Secreted as inactive
pro-enzyme in stomach but activated in lumen of GI tract.
- Exopeptidase release single amino acid by cutting them of the ends. Most important
digestive exopeptidases are the two isozymes of carboxypeptidase secreted by pancreas.
Fats
Vital as energy source, for insulation and protection of organs, and absorption and transport of fat-
soluble vitamins. Broken down into fatty acids and glycerol. Functions: (1) cell membrane health, (2)
storing energy, (3) transport and absorption, and (4) insulation.
- Saturated fat include trans fats. Stay solid and
cause fatty deposits in blood vessels. Increase
level of “bad” cholesterol (low-density
lipoprotein).
- Unsaturated fat have a double bond. Stay
liquid at room temperature and are less likely to
clog arteries. Increase level of “good” cholesterol
(high-density lipoprotein). HDL escorts LDL to the
liver where it is broken down and removed from the body.
o Mono or poly, can have one or more than one double bond.
Breakdown
Starts with emulsification by bile acid, resulting in large droplets cleaved into smaller droplets
increasing surface area. Fats are consumed as triacylglycerol (TAG), which is digested in the
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gastrointestinal lumen. Digestive products are taken up by enterocytes, and resynthesized to TAG,
and packaged into chylomicrons (CM) for secretion or in cytoplasmic lipid droplets (CLDs) for storage.
- Ester bonds in TAG is hydrolyzed by lipases, resulting in FAs and 2-MAG, which are emulsified
by bile acids and phospholipids, forming micelles.
- All regions in the small intestine are able to uptake and absorb digestive products of TAG.
Jejunum takes up the majority.
- CD36 and LFBAP are transport proteins involved with fatty acid entry into the enterocytes
and its intracellular movement.
- Once taken up, FA-binding proteins transport FAs to the cytoplasm which are utilized for FAG
synthesis.
- FAs are activated in ER to fatty acyl-CoAs by acyl-CoA synthetase (ACS).
- DAG is synthesized from 2-MAG and a fatty acyl-CoA by monoacylglycerol acyltransferase
(MGAT). TAG is synthesized from DAG and a fatty acyl-CoA by diacylglycerol acyltransferase
(DGAT).
Chylomicrons the major TAG-rich lipoprotein produced in response to dietary fat. Synthesized in
ER and transported through Golgi and secretory pathway via pre-CM transport vesicles to the
basolateral side of enterocyte where they enter the lymphatics.
- Deliver dietary FAs to tissues throughout the body through lipoprotein lipase activity, which
hydrolyzes TAG in the core of the CM at the surface of parenchymal cells releasing FAs for
uptake.
Cytoplasmic lipid droplets when TAG levels are high, TAG is incorporated into CLDs and stored
temporarily in enterocytes. Majority of CLDs are present in upper jejunum.
Influence of tumors on digestion
Nearby pancreatic duct pancreatic duct transports pancreatic enzymes made by pancreas to
upper part of duodenum. Results in lack of pancreatic enzymes for digestion of food due to the
pressure of the tumor on the duct, resulting in incomplete digestion of all three macronutrients.
Nearby pancreas pancreas synthesizes pancreatic enzymes needed for digestion of food. Tumor
can infect one or more enzymes, resulting in incomplete digestion of one or more macronutrients.
Microbiome
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