Multiple Roles of Carbohydrates in All ABSORPTION Forms of Life: 60% - starches and dextrins. Starch is a 1. CHO serves as energy stores, fuels glucosan or glycan (composed of and metabolic intermediates. It is the glucose ONLY) preferred source of energy by the HOMOPOLYSACCHARIDE; most organism –gives 4kcal/gm, 36 or 38 important food source of CHO: moles of ATP per mole of glucose. 30% - sucrose 2. Ribose and deoxyribose sugars form 5% - lactose part of the structural framework of 5% - other sugars DNA and RNA. 3. Polysaccharides are structural A. Digestion in the MOUTH elements in the cell walls of bacteria - ENZYME: Salivary Amylase or and plants, and in the exoskeletons of PTYALIN arthropods. - Bonds acted upon: alpha 1,4- Cellulose is the main constituent of glycosidic linkages of plant cell walls; it is the most abundant amylopectin and amylase organic compound in the biosphere. - Optimum pH: 6-7 (readily 4. CHO are linked to many proteins inactivated at pH4.0 or less) and lipids forming glycoconjugates - End products: limit dextrin and (proteoglycans, glycoproteins, maltose glycolipids) which can serve as recognition sites for hormones, B. Digestion in the STOMACH antigen specificity, etc. - No enzymatic digestion (due to 5. CHO can generate reducing acidity) equivalents in the form of NADPH, - Limited acid hydrolysis which is essential in the biosynthesis of important cellular components like C. Digestion in the SMALL INTESTINES lipids, steroids, DNA, etc. - ENZYME: Pancreatic Amylase or AMYLOPSIN - Alpha-limit dextrinase - Sucrase - Lactase (β-galactosidase) - Maltase (α-glucosidase) - Isomaltase (α1,6-glucosidase) *IRREVERSIBLE reaction.
END PRODUCT OF CHO DIGESTION: *meaning you cannot use the same
Monosaccharides (principally enzyme for the forward and backward.
GLUCOSE) *It is possible to convert GLUCOSE-6-
PHOSPHATE → GLUCOSE using ABSORPTION OF CARBOHYDRATES another enzyme (Glucose-6- Rate of monosaccharide absorption: Phosphatase, which is only found in (MOST rapid to LEAST rapidly the liver); conversion is only done in absorbed) the liver. Galactose → Glucose → Fructose → Mannose → Pentoses *The reaction above is a PHOSPHORYLATION REACTION. Fates of Ingested Glucose: - 50% - converted to energy (glycolysis) HEXOKINASE GLUCOKINASE - 30-40% - converted to fats Low Km for High Km for - 10% - converted to glycogen (stored glucose glucose in muscles and liver) - can act even - function only glucose level is when the LOW concentration of *INSULIN: facilitates entry of glucose glucose is high - cannot act if inside the cell. EXCEPT in LIVER CELLS; glucose level is low glucose can enter the liver cell even Inhibited by high Not inhibited by without insulin because liver is the levels of glucose- glucose-6- most important organ for the control 6-phosphate phosphate (feedback of blood sugar. inhibition)
Acts on other Acts on glucose
FIRST REACTION undergone by hexoses general ONLY enzyme(fructose, GLUCOSE once inside the cells: mannose etc) - Major pathway for the utilization - Enzymes are NOT used at the of glucose; found in all cells same time. FIRST- Hexokinase - Unique pathway: can utilize - FEEDBACK INHIBITION: the oxygen if available (AEROBIC); enzyme is inhibited by its own can still function in the absence product. of oxygen (ANAEROBIC) - Once hexokinase is inhibited by - Converts GLUCOSE to ↑ glucose-6-phosphate, PYRUVATE (AEROBIC end- glucokinase is the only one will product) and LACTATE act. (ANAEROBIC end product) with concomitant production of ATP Fate of GLUCOSE-6-PHOSPHATE: - Location: CYTOSOL - “Basically” an EXERGONIC 1. Conversion to GLYCOGEN for process (production of ATP) storage (10%) -meaning there is a part in the 2. Enters GLYCOLYSIS (50%) pathway that is endergonic and 3. Conversion to fatty acids and exergonic. cholesterol 4. Conversion to blood glucose ➔ Exergonic (ATP production) is 5. Oxidative degradation to CO2 → more than endergonic (ATP is energy formation (KREB’S used). CYCLE) -continuation of #2; for maximum FUNCTIONS of Glycolysis: energy production - To produce energy in the form 6. Degradation via HMP shunt of ATP 7. Enters uronic acid pathway - Intermediates formed can be converted to other substances GLYCOLYSIS: “Embden-Meyerhof- like amino acids, fatty acids, etc. Parnas Pathway” - Gustav Embden, Otto Meyerhof, TWO PHASES OF GLYCOLYSIS Jacob Parnas 1. Energy INVESTMENT phase; PRIMING STAGE - Endergonic Glucose → Fructose - ENZYME: Hexokinase, 1,6-bisphosphate Glucokinase 2. Energy GENERATION phase; - use of 1 ATP ENERGY RECOVERY PHASE - Phosphorylation reaction - Exergonic; Production of ATP 2. SECOND REACTION: Reversible A. SPLITTING STAGE Fructose 1,6- - ISOMERIZATION REACTION: an bisphosphate → DHAP + aldose is converted into a ketose glyceraldehydes-3-PO or vice versa Ex: Glucose-6-phosphate ↔ Fructose-6- B. OXIDOREDUCTION- phosphate PHOSPHORYLATION STAGE -ENZYME: Phosphoglucose Isomerase glyceraldehydes-3-PO4→ Pyruvate or Lactate 3. THIRD REACTION: (2nd) Irreversible - use of 1 ATP - Phosphorylation reaction “IN GLYCOLYSIS, all the IRREVERSIBLE - RATE LIMITNG STEP STEPS are CONTROL POINTS!” (Committed Step) -most important CONTROL POINT of CONTROL POINT: the pathway - if you want to STIMULATE the - RATE LIMITING pathway, stimulate the enzymes - ENZYME: Phosphofructokinase of the control point. 1 (PFK 1) - if you want to INHIBIT the pathway, inhibit the enzymes of SUMMARY: the control point. A. There are 2 IRREVERSIBLE steps. 1. ENERGY INVESTMENT PHASE B. 2 ATPs are used. (PRIMING STAGE) C. No ATP production. - FIRST REACTION: (1st) Irreversible II. ENERGY GENERATION PHASE A. SPLITTING STAGE - FOURTH REACTION: Fructose-1- - produces NADH (whenever NADH is 6-Bisphosphate (6 carbons) produced, it has to go back to NAD so SPLITS into 2 sugars: that the pathway will go on; if NAD+ were not regenerated, glycolysis could Dihydroxyacetone phosphate (3 not proceed beyond glyceraldehyde-3- carbons) phosphate, which means no ATP Glyceraldehyde-3-phosphate (3 would be generated.) carbons) - H + is given to Electron Transport - SPLITTING ENZYME: Aldolase Chain (ETC) in the mitochondria (aldo-cleavage) - Dihydroxyacetone (DHAP) - from the CYTOSOL, it has to go to the phosphate and Glyceraldehyde- MITOCHONDRIA through a shuttle 3-phosphate are system. INTERCONVERTIBLE. - ISOMERIZATION REACTION SHUTTLE SYSTEM: Malate-Aspartate (Complex1); Glycerol-3-phosphate B. OXIDOREDUCTION- (Complex2) – MASS: 3 ATP produced x2 PHOSPHORYLATION STAGE = 6 ATP - whatever happens to G3PSS: 2 ATP produced x2 = 4 ATP Glyceraldehyde-3-phosphate, also happens to DHAP SIXTH REACTION: - energy produced in 1,3 Diphosphoglycerate → 3- Glyceraldehyde-3-phosphate, phosphoglycerate MULTIPLY by 2. ENZYME: Phosphoglycerate Kinase - 1 ATP produced x2 =2 ATP FIFTH REACTION: SUBSTRATE LEVEL OF - conversion of Glyceraldehyde-3- PHOSPHORYLATION: energy phosphate → 1,3 Diphosphoglycerate production even without entering ETC ENZYME: Glyceraldehyde-3-phosphate Dehydrogenase SEVENTH REACTION: 3-phosphoglycerate→2-phosphoglycerate ENZYME: Phosphoglyceromutase - First reaction (catalyzed by Hexokinase, Glucokinase) EIGHTH REACTION: - Third reaction (catalyzed by 2- Phosphofructokinase 1) –RATE phosphoglycerate→Phosphoenolpyruv LIMITING STEP ate - Ninth reaction (catalyzed by ENZYME: Enolase Pyruvate Kinase) Enolase is inhibited by FLUORIDE - DEHYDRATION STEP ➔ If it becomes ANAEROBIC (No ETC), NADH will be used to NINTH REACTION: (3rd) Irreversible convert PYRUVATE → LACTATE. - Phosphoenolpyruvate → ➔ ENZYME: Lactate Pyruvate Dehydrogenase ENZYME: Pyruvate Kinase ➔ In ANAEROBIC GLYCOLYSIS, - 1 ATP produced x2 =2 ATP end-product is LACTATE. SUBSTRATE LEVEL OF PHOSPHORYLATION ENZYMATIC CONTROL OF GLYCOLYSIS: SUMMARY: - Inhibit/Stimulate at CONTROL 2 substrate level of phosphorylation POINTS - 1st – catalyzed by 1. HEXOKINASE Phosphoglycerate Kinase (Sixth - Inhibited by Glucose-6- reaction) phosphate - 2nd – catalyzed by Pyruvate 2. PHOSPHOFRUCTOKINASE 1 Kinase (Ninth reaction) (PFK1) - MAJOR CONTROL ENZYME of 1 oxidative phosphorylation glycolysis - Fifth reaction 3. PYRUVATE KINASE
3 irreversible steps = CONTROL INHIBITORS OF THE GLYCOLYTIC
POINTS! PATHWAY 1. 2-DEOXYGLUCOSE - catalyzed by Pyruvate - Inhibits HEXOKINASE Dehydrogenase Complex (has 5 2. SULFHYDRYL REAGENTS steps of reactions) (iodoacetate) - Inhibits GLYCERALDEHYDE-3- PHOSPHATE DEHYDROGENASE 3. FLUORIDE - Inhibits ENOLASE (catalyzes the dehydration step) 4. 4 PENTAVALENT ARSENIC or ARSENATE - Inhibits PYRUVATE DEHYDROGENASE, and α- KETOGLUTARATE DEHYDROGENASE
FATES OF PYRUVIC ACID
1. Reversible reduction to LACTATE - if the condition is ANAEROBIC 2. Conversion back to GLUCOSE 3. Formation of OXALOACETATE or MALATE 4. Transamination to form ALANINE - Pyruvate + Amino group = Alanine 5. Oxidative decarboxylation to Acetyl CoA - MAJOR FATE OF PYRUVIC ACID - it will be converted to Acetyl CoA