Biochemistry Lecture Week 14 PDF

Biochemistry Lecture / Week 14 / Prof. Rogelda Bongat Leila Javier (2MT-N) DIGESTIVE ENZYMES PRESENT IN THE SALIVA ESSENTIALS OF DIGESTION Salivary Amylase DIGESTION...

Biochemistry Lecture / Week 14 / Prof. Rogelda Bongat Leila Javier (2MT-N) DIGESTIVE ENZYMES PRESENT IN THE SALIVA ESSENTIALS OF DIGESTION Salivary Amylase DIGESTION - primary enzyme in saliva; breaks down Digestion carbohydrates into smaller molecules, - the process of breaking down food by like sugars; mechanical and enzymatic action in the - During this process, larger carbohydrates, alimentary canal into substances that called amylopectin and amylose, are can be absorbed and used by the body broken down into maltose - starts with the mouth, where amylase - Maltose is a sugar composed of subunits and lipase are present of glucose, the human body's key source - from the mouth, it will be broken down of energy. into smaller pieces going down to the o A disaccharide broken down in esophagus to the stomach, enters the the smaller intestine into duodenum, jejunum, and ileum of small monosaccharides intestine, then cecum and goes up to Lingual Lipase the ascending colon then transverse - breaks down triglycerides into glycerides colon, descending colon, sigmoid colon, and fatty acid components, thus rectum, and finally anus. catalyzing the digestion of lipids. - Most of the digestion happens in the - can operate at lower pH values, action small intestine continues into the stomach. - helps infants digest the fats in their mother's milk; the relative proportion of lingual lipase in saliva decreases as we grow older, as other parts of our digestive system help with fat digestion - Other lipases for lipids: gastric lipase (exists in small amounts) and pancreatic lipase (from pancreas) THE GASTROINTESTINAL TRACT 1. Sublingual and submandibular salivary glands 2. Esophagus 3. Stomach 4. Duodenum 5. Jejunum 6. Ileum 7. Cecum - Mouth – for mechanical digestion of 8. Ascending Colon food 9. Transverse Colon - Liver – contributes to digestion by 10. Descending Colon producing bile which is important for the 11. Sigmoid Colon emulsification of fats 12. Rectum - Gallbladder – storage site of bile 13. Anus 1 | Biochemistry | Lecture | Week 14 | Leila Javier (2MT-N) o When we eat fatty foods, the - Stomach – no enzymatic digestion but gallbladder will contract to mechanical breakdown occurs → mix release bile CHO into more uniform mixture of CHYME - Small Intestine: Chyme → pancreatic OVERVIEW OF CARBOHYDRATE DIGESTION juice 1. Mouth: The enzyme salivary amylase - Dextrins + Pancreatic amylase → shorter begins breaking down starch into shorter CHO chains polysaccharides - Disaccharidases: Sucrase, Lactase, and o Mechanical digestion of food Maltase 2. Stomach: Salivary amylase is inactivated o Sucrose + Sucrase → glucose + and no further carbohydrate digestion fructose occurs o Lactose + Lactase → galactose + 3. Small intestine: Majority of starch glucose digestion and breakdown of o Maltose + Maltase → glucose + disaccharides occur here. The enzyme glucose pancreatic amylase breaks down starch - In the liver: into monosaccharides, disaccharides, o Galactose converted to glucose and oligosaccharides. o Fructose broken to smaller 4. The digestion of carbohydrates is carbon units completed by the enzymes o Glucose stored as glycogen or (disaccharidases) attached to the brush exported back to the blood border of the intestinal villi. Here, the - Carbohydrate digestion begins in the disaccharides are broken down into mouth and is most extensive in the small monosaccharides. intestine. 5. Large intestine: Fiber and other - The resultant monosaccharides are indigestible carbohydrates are partially absorbed into the bloodstream and broken down by bacteria to form short transported to the liver. chain fatty acids and gas. The remaining fiber is excreted in the feces. PROTEIN DIGESTION 1. Whole proteins are chewed and swallowed into the stomach - Large intestine – site for the indigestible 2. Hydrochloric acid denatures proteins, (usually broken down by bacteria); not unfolding their 3-D structure to reveal the much absorption happening polypeptide chain - Stomach – mechanical digestion also o Stomach pH = 1.5-3.5, highest is 4 occurs → peristalsis 3. Enzymatic digestion by pepsin forms - Chyme – fluid digested food → will be shorter polypeptides converted to pancreatic juice o The 3D structure will be converted into polypeptide chains which will Carbohydrate Digestion and Absorption be further digested by pepsin - Amylose and amylopectin + Salivary (inactive form: pepsinogen) in the amylase → Dextrin + maltose stomach o Occurs in the stomach 2 | Biochemistry | Lecture | Week 14 | Leila Javier (2MT-N) 4. In the small intestine, trypsin, 1. Glucose chymotrypsin, and proteases continue 2. Fats enzymatic digestion, forming tripeptides, 3. Proteins dipeptides, and amino acids - If there is not enough glucose or energy 5. In enterocytes, tripeptides and available: dipeptides are further broken down into o Amino acids are rearranged into amino acids, which are absorbed into glucose for fuel of brain and red the blood blood cells o To enter the enterocytes, they ▪ Brain and red blood cells need active transport system ONLY use glucose as a (needs energy) source of energy o Absorbable form of protein → ▪ Low glucose levels → amino acids hypoglycemia o Absorbable form of o Metabolized as fuel, for an carbohydrates → immediate source of ATP monosaccharides LIPID DIGESTION AND ABSORPTION - In the mouth: mechanical digestion, mixing with saliva, limited enzymatic digestion (lingual lipase) 1. A small amount of lipid digestion occurs in the stomach due to the gastric lipase produced in the stomach o Gastric lipase only exists in small amounts 2. Bile is produced in the liver, stored in the gallbladder, and released into the small intestine to aid in the digestion and - from the blood, the amino acids are absorption of lipids transported to the liver → become part o The bile will emulsify the fat to of the amino acid pool form micelles - If the body has enough glucose and 3. The enzyme pancreatic lipase is other source of energy, amino acids will produced by the pancreas and released be used for the following: into the small intestine to break down o Protein synthesis in cells triglycerides into monoglycerides, fatty o Produce nonessential amino acids, and glycerol acids for protein synthesis 4. In the small intestine, the products from o Synthesis of other nitrogen- fat digestion and bile acids form a containing compounds micelle, which moves toward the o Rearranged and stored as fat microvilli to allow the lipids to diffuse into ▪ If you have excess the mucosal cells proteins, it will be 5. Inside the mucosal cells, the fatty acids converted into fats and monoglycerides are resembled into ▪ It cannot be stored as triglycerides and incorporated into lipid proteins/amino acids transport particles called chylomicrons, ▪ If you need energy, it will which enter the lymph vessel undergo gluconeogenesis 6. The small intestine is very efficient in Gluconeogenesis absorbing fat so very little is normally – producing excreted in the feces. glucose from non- carbohydrate sources such as proteins and fats ▪ Order of energy sources: 3 | Biochemistry | Lecture | Week 14 | Leila Javier (2MT-N) - Once inside the intestinal cell, short- and medium-chain fatty acids and glycerol Lipid Digestion and Absorption in the Small can be directly absorbed into the blood Intestine stream 1. Emulsification by bile - Long chain fatty acids and o Large fat droplet + bile → monoglycerides reassemble into emulsified fat droplet triglycerides within the intestinal cell, and 2. Enzymatic digestion by pancreatic lipase along with cholesterol and fat-soluble o Triglyceride –(lipase)→ vitamins are incorporated into transport monoglycerides + fatty acids vehicles called chylomicrons 3. Absorption of products of fat digestion - Chylomicrons are large structures with a depends on the size core of triglycerides and cholesterol and o Short and medium-chain fatty an outer membrane made up of acids and glycerol (small phospholipids interspersed with proteins products) → absorbed into blood (apolipoproteins) and cholesterol via capillary - The outer membrane makes them water o Long-chain fatty acids and soluble so that they can travel in the monoglycerides (large products) aqueous environment of the body → form into triglycerides and are - Chylomicrons from the small intestines transported in chylomicrons into travel first into the lymph vessels which lymph vessels then deliver them to the blood stream - Fatty acids and monoglycerides via the jugular vein (resulting from fat digestion) leave micelles and enter epithelial cell STOMACH - Fatty acids link to form triglycerides - The stomach consists of 3 major zones: - Fatty globules combine with proteins to o Cardiac zone form chylomicrons (inside Golgi o Body apparatus) o Pyloric zone - Chylomicrons are extruded from the ▪ Antrum epithelial cell and enter a lacteal (lymph ▪ Pyloric canal & sphincter capillary) - End product is chyme - Lymph in the lacteal transports chylomicrons away from intestine 4 | Biochemistry | Lecture | Week 14 | Leila Javier (2MT-N) Specialized Cells in the Stomach and their o Gastric inhibitory polypeptide Secretion (GIP) Specialized Secretion Function ▪ Inhibits production of HCl cells of parietal cells Protects the Columnar stomach from o Secretin cells/foveolar Mucus digestive juice and ▪ Stimulates the release of cells (in the provides slippery the sodium bicarbonate lining surface that helps to neutralize the acid in epithelia) food move the small intestine through the stomach o Vasoactive intestinal polypeptide HCl Helps breakdown (VIP) food; kills bacteria ▪ Inhibits acid secretion and other o pH 1.5 or less Parietal cells microorganisms ▪ negative feedback → inhibit parietal cells to IF (intrinsic Promotes factor) absorption of Vit. release HCl B12 in the ileum Chief cells Pepsinogen Converts to pepsin SMALL INTESTINE with HCl; digest - The small intestine is of 3 parts protein Neuroendocrine Cells G-cells Gastrin Stimulates ECL to release histamine ECL-like cells Histamine Increase HCl (Enterochro- secretion (by maffin-like parietal cells) cells) D-cells (Delta Somatostatin Inhibit gastrin and cells) production of HCl EC-cells Regulate GIT (Enterochro- Serotonin motility and fluid maffin cells) secretion Hunger hormone; P/D1 cells Ghrelin increases appetite Duodenum and promote fat storage - Shortest region (10 in.) - final chemical digestion (pancreatic and brush border enzymes are emptied here) What stimulates stomach secretions? - Absorption of iron and folate - Gastric secretions occur in response to various stimuli: Jejunum o Neurogenic stimuli - 3 ft. long ▪ Stimulates vagus nerve to - Major site of nutrient absorption: CHO release HCl (carbohydrates), CHON (proteins), fats, o Distension of the stomach minerals and vitamins. ▪ Also stimulates vagus - Circular folds → villi → microvilli → nerve to release HCl capillaries/ lacteals o Contact with secretagogues Ileum ▪ Secretagogues stimulates - 6 ft. long and joins the large intestine the secretion of other - Absorbs bile acids, fluid, and vit. B-12 substances o Gastrin SMALL INTESTINE: Digestion of Carbohydrates ▪ Stimulates the release of - Pancreatic AMS Histamine - Brush-Border Enzymes o 𝛼-dextrinase Regulation of Gastric secretions: ▪ Digests dextrins - Reduces gastric acid secretion: o Sucrase o Maltase 5 | Biochemistry | Lecture | Week 14 | Leila Javier (2MT-N) o Lactase Cuts at the ▪ Lactose Intolerance: ↓↓ carboxyl terminal lactase ▪ Aminopeptidase Diarrheic stool Cuts at the amino Bloating terminal Metabolic acidosis - Brush border enzymes: ▪ Lactose Intolerance – o Aminopeptidase cannot digest lactose o Dipeptidase because of absence or SMALL INTESTINE: Digestion of Lipids reduced lactase ▪ There are special preparation of milk that do not contain lactose ▪ Acquired lactose deficiency → temporary ▪ Genetic lactose - Triacylglycerol (TAG) and deficiency → permanent polyacylglycerol (PAG) converted by lipases to fatty acids and monoacylglycerol, which will be absorbed and go to the lacteals - Enzymes that spilt up TAG and Phospholipids are lipases o Lingual lipase o Gastric lipase o Pancreatic lipase - Fat emulsification (bile) o no bile no digestion - Absorbed in lacteals SMALL INTESTINE: Digestion of Nucleic Acids - Nucleic acids are consumed in large quantities as nucleoproteins due to their - Lactose Intolerant: lactose → bacterial presence in all cells fermentation → acid and gas - Nucleoproteins = conjugated proteins o Irritation is caused and results to: with amino acids + nucleic acids ▪ Flatulence (prosthetic part) ▪ Acidemia - Not utilized by the body but digested, ▪ Diarrhea catabolized and excreted - Enzymes used: SMALL INTESTINE: Digestion of Proteins - Protein digestion starts in the stomach o Ribonucleases o Deoxyribonucleases o Phosphatases (for phosphate bonds) - Pancreatic Enzymes: o Endopeptidases: they lyse the bonds between peptides within the chains ▪ Trypsin ▪ Chymotrypsin ▪ Elastase o Exopeptidases: cuts at the terminal ends ▪ Carboxypeptidase 6 | Biochemistry | Lecture | Week 14 | Leila Javier (2MT-N) - Nucleoprotein: proteolytic enzymes of o Production of pancreatic juice gastric and pancreatic juice → will o Stimulus: acidic gastric contents remove amino acids and produce o Inhibits Gastrin secretion nucleic acid - Cholecystokinin - Nucleic Acid: RNAse and DNAse of o Enteroendocrine cells pancreatic and intestinal juice → o Stimuli: amino acids and fatty produces nucleotide acids - Nucleotide: Nucleotidase (intestinal o Gallbladder contraction to phosphatase) → hydrolyzed and will release bile, Release of produce phosphate + nucleoside pancreatic enzymes (acini) - Nucleoside: Tissue nucleosidase → absorbed and taken to liver, kidney, METABOLISM (PART I) spleen, bone marrow → free purine or Metabolism pyrimidine + ribose or deoxyribose - Biochemical processes by which all living - Purine is metabolized to form Uric Acid organisms sustain life - The sum of all chemical reactions that LARGE INTESTINE occur in the body - 5 ft. long, distal ileum to anus - Require the use of enzymes and - Cecum, colon, sigmoid, rectum and anal coenzymes canal - Storage of: METABOLISM BASICS o Undigested food particles will be Metabolism acted upon by bacteria: - The sum of all chemical reactions that ▪ CHO → gases occur in the body ▪ CHON → amino acids → - Require the use of enzymes and indole, skatole, H2S coenzymes (cause of foul odor of General Classification of chemical reactions stool) - Anabolic: ▪ Bilirubin → stercobilin o Those that create larger - Reabsorption of: molecules via biosynthesis or o Water absorption: 1L (200mL) reduction o Sodium, chloride and some o Ex. glycogenesis vitamins (K, B6, B12) o All processes with -genesis are PANCREAS anabolic processes o Reduction reactions – gain of H⁻ - Digestive accessory gland - 99% exocrine; glandular cells ions - Pancreatic juices - Catabolic: o Water, salts, sodium bicarbonate, o Those that breakdown larger and enzymes molecules into smaller molecules; o Sodium bicarbonate biomolecules are being ▪ Buffers acidic gastric juice degraded or oxidized ▪ Stops the action of pepsin o Ex. glycogenolysis ▪ Optimum pH for o All processes with -lysis are pancreatic and brush catabolic processes border enzymes o Oxidation reactions – loss of H⁻ - 1% endocrine: Islets of Langerhans cells ions o Insulin (beta cells) o Glucagon (alpha cells) o gastrin in pancreatic cell tumors o somatostatin (delta cells) Regulation of Pancreatic Secretions - Secretin o Enteroendocrine cells 7 | Biochemistry | Lecture | Week 14 | Leila Javier (2MT-N) - Anabolic: Small molecules are - These bonds can then be broken to yield assembled into large ones. energy, thus driving the metabolic o Energy is required processes of life. - Catabolic: Large molecules are broken - Hydride ions can be transferred from one down into small ones. intermediate to another resulting in a net o Energy is released oxidation or reduction of the intermediate. Anabolic or Catabolic? - Oxidation corresponds to a loss of - Anabolic: hydride and reduction to the gaining of o Photosynthesis hydride o Glycogenesis - Certain reduced forms of high energy o Translation processes molecules such as NADH and [FADH₂] o DNA replication (anabolic since can donate their electrons to the you are making copies) electron carriers of the electron transport o Amino acids to protein chain (ETC) which results in the - Catabolic: production of ATP (only under aerobic o Glycogenolysis conditions). o Glycolysis o Protein to amino acids ATP (Adenosine Triphosphate) - comprises high energy bonds located Anabolic Processes Catabolic Processes between each phosphate group. Gluconeogenesis Glycolysis - These bonds are known as phosphoric Pentose Phosphate Beta Oxidation anhydride bonds. Pathway - Is a nucleotide consisting of an adenine Fatty acid and Kreb’s Cycle base attached to a ribose sugar, which is Isoprenol/Sterol Synthesis attached to three phosphate groups Electron Transport Mechanism Fermentation Anabolism - Building up - Energy-consuming (endergonic) - Assembles more complex molecules from simpler ones Catabolism - Breaking down - Energy-producing (exergonic) - ATP hydrolysis: - To produce simple molecules for o Hydrolysis of the terminal synthesizing others phosphate group by ATPase releases of 30.5 𝑘𝐽/𝑚𝑜𝑙−1 of free IMPORTANT HIGH ENERGY MOLECULES IN energy METABOLISM o H₂O (from the water added) - The complex processes of metabolism becomes H⁺ and OH wouldn't be possible without the o Products are inorganic assistance of certain high-energy phosphate (won’t be doubly molecules. protonated at neutral pH) and - The main purpose of these molecules is Adenosine Diphosphate (ADP) to transfer either inorganic phosphate groups (Pi) or hydride (H-) ions. - The inorganic phosphate groups are used to make high energy bonds with many of the intermediates of metabolism. 8 | Biochemistry | Lecture | Week 14 | Leila Javier (2MT-N) o NADH → received H → reduced (anabolism) Dehydration-Hydrolysis - Uses hydrolase class of enzymes - Removing water to create larger molecules (Dehydration) - Adding water to split larger molecules into smaller molecules (Hydrolysis) - Anabolic metabolism is generally a dehydration reaction - The chemical reactions in metabolic - Catabolic metabolism is generally a pathways don’t take place hydrolysis reaction automatically, without guidance. - - Instead, each reaction step in a pathway is facilitated, or catalyzed, by a protein called an enzyme. SPECIAL TYPES OF METABOLIC REACTIONS Oxidation-Reduction - A coupled reaction in which electrons are transferred from one molecule to another - In the hydrolysis of carbohydrates, water - This is a MAJOR player in the ATP molecules are used to lyse (break) production pathway glycosidic bonds. - Mediated by oxidoreductase class of enzymes Addition-Subtraction-Exchange - Anabolic metabolism is generally a - Transferases – mediate exchanges reduction reaction - Lyases – mediate addition/removal - Catabolic metabolism is generally an - The addition, removal or exchange of oxidation reaction chemical groups between molecules - Oxidation: - Carboxylation – Decarboxylation: o Transfers electrons from a o Carboxylation – add carboxyl molecule to oxygen (removes e⁻) group → anabolic o Removes H+ o Decarboxylation – remove o A catabolic pathway carboxyl group → catabolic - Reduction: - Phosphorylation – dephosphorylation: o The gain of electrons from a o Phosphorylation – add phosphate molecule → anabolic o An anabolic pathway o Dephosphorylation – remove - Example: Glyceraldehyde 3-phosphate is phosphate → catabolic oxidized (and phosphorylated) to 1,3- Bisphosphoglycerate o Glucose + PO₄ → Glucose 6- phosphate ▪ Hexokinase → phosphorylation o Glyceraldehyde 3-phosphate → ▪ Anabolic process donated H → oxidized o Glucose 6-phosphate → Glucose (catabolism) + PO₄ 9 | Biochemistry | Lecture | Week 14 | Leila Javier (2MT-N) ▪ Glucose 6-phosphatase → dephosphorylation ▪ Catabolic process Ligation Reactions - Molecular groups are joined using energy - Uses ligase class of enzymes - Ex. Formation of acetyl CoA, succinyl CoA -----------------------------------END---------------------------- Based on ppt and discussion notes Italicized = Discussion notes 10