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Carbohydrate Metabolism (LEC)
BIOCHEMISTRY (CHM3)
Our Lady of Fatima University
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CARBOHYDRATE METABOLISM
RECALL: Different stages of metabolism 1. Digestion 2. Formation of Acetyl-CoA 3. Krebs Cycle 4. Electron Transport chain and Oxidative phosphorylation
DIGESTION OF CARBOHYDRATES Carbohydrates, especially glucose, play major roles in cell metabolism. The major function of dietary carbohydrates is to serve as a source of energy.
- In a typical diet, 2/3 of daily energy needs are furnished by carbohydrates.
- During carbohydrate digestion, disaccharides and polysaccharides are hydrolyzed to form monosaccharides, primarily glucose, fructose, and galactose:
- After digestion is completed, glucose, fructose, and galactose are absorbed into the bloodstream through the lining of the small intestine and transported to the liver.
- In the liver, fructose and galactose are rapidly converted to glucose or to compounds that are metabolized by the same pathway as glucose.
BLOOD SUGAR LEVELS Glucose is the most plentiful monosaccharide in blood. The term blood sugar usually refers to glucose (food of the cell) In adults, the normal blood sugar level measured after a fast of 8-12 hours is 70-110 mg/100 mL (in clinical reports the units are in mg/dL). The blood sugar level reaches a maximum of about 140-160 mg/100 ml about 1 hour after a carbohydrate-containing meal , and returns to normal after 2-2 hours.
Hypoglycemia occurs when blood sugar levels are below the normal fasting level. o Hypogly - Gutom na gutom o Common fr=first aid – eat sweets or candy
Mild hypoglycemia leads to dizziness and fainting as brain cells are deprived of energy. Severe hypoglycemia can result in convulsions and shock.
Hyperglycemia occurs when blood sugar levels are above the normal fasting level - If blood glucose levels are above 180 mg/ mL, the sugar is not completely reabsorbed by the kidneys, and glucose is excreted in the urine. - The blood glucose level at which this occurs is the renal threshold, and the condition when glucose appears in the urine is called GLUCOSURIA – indicative of liver damage - Prolonged hyperglycemia at a glucosuric level indicates a problem with the body's normal ability to control blood sugar levels.
BLOOD SUGAR LEVELS AND THE LIVER
The liver is the key organ involved in regulating blood glucose levels. - When blood glucose levels rise after a meal , the liver removes glucose from the bloodstream , and converts it to glycogens or triglycerides for storage.
- When blood glucose levels are low , the liver converts stored glycogen to glucose , and synthesizes new glucose from noncarbohydrate sources (gluconeogenesis)
GLYCOLYSIS/ GLYCOLITIC PATHWAY
- First thing happens after the glucose absorbed by the cell, it would be converted into two molecules of PYRUVATE
- Is a series of ten reactions, with a net result of converting a glucose molecule into two molecules of pyruvate
Product: 1 st step (Energy Expenditure Stage): 2 ATP 2 nd step (Generating stage): 4 ATP 1 mole of glucoses= 2 moles of ATP 1 mole of maltose= 4 moles of ATP Sucrose= 2 ATP (since it would be fructose)
REGULATION OF GLYCOLYSIS Catabolic process All of the enzymes in the glycolysis pathway are found in cellular cytoplasm. The net result of adding all of these reactions together gives the equation: glucose + 2P, + 2ADP + 2NAD*
Note: o Carbohydrates commonly found as polymer (polysaccharides) and there are joined by glycosidic linkage and this linkage is broken down by a special enzyme o Starch = Amylose (Alpha 1- 4 link) & Amylopectin (Alpha 1-4 and 1-6 which is distinct poses the branching of monosaccharides) broken down by salivary amylase that catalyzes the hydrolysis of polysaccharides into monomer units o Lactose (Milk sugar) o Sucrose (Table sugar) o Glucose (blood sugar) o Maltose (Malt sugar)
From C6 to C
2 pyruvates + 2ATP + 2NADH + 4H + 2H*
- There is a net gain of 2 moles of ATP for every mole of glucose that is converted to pyruvate.
Other sugars are also digested in glycolysis:
- Fructose enters glycolysis as dihydroxyacetone phosphate and glyceraldehyde-3-phosphate.
- Galactose is isomerized to form glucose-6- phosphate.
The glycolysis pathway is regulated by three enzymes (gate keepers): 1. HEXOKINASE - catalyzes the conversion of glucose to glucose-6- phosphate and initiates the glycolysis pathway. The enzyme is inhibited by a high concentration of glucose-6-phosphate (feedback inhibition). 2. PHOSPHOFRUCTOKINASE - catalyzes the irreversible conversion of fructose 6- phosphate to fructose 1,6- bisphosphate As an allosteric enzyme, it is inhibited by high concentrations of ATP and citrate , and activated by high concentrations of ADP and AMP. 3. PYRUVATE KINASE - catalyzes the conversion of 3- phosphoenolpyruvate to pyruvate. This is an allosteric enzyme that is inhibited by high concentrations of ATP.
When the glycolysis pathway is operating, so are the citric acid cycle and the electron transport chain, which produce large amounts of ATP.
- If ATP use decreases, the concentration of ATP increases. The ATP binds to phosphofructokinase and pyruvate kinase, slowing down their activity, and thus slowing the glycolysis pathway.
- When ATP concentrations are low, ADP and AMP concentrations are high, which activates the phosphofructokinase, accelerating the glycolysis pathway
Kinase = phosphate group functional group Regulated by Feedback Inhibition , meaning if there are many ATPs those enzymes are inhibited because there is no need of energy basically, slow down the process because of high concentration of ATP but it is activated if there is low concentration or not enough ATP – primarily by the regulation of Allosteric o Allosteric site would interact to ADP or citrate imposing a confirmational change in the enzymes. Thus, it would regulate the process
THE FATE OF PYRUVATE The sequence of reactions that convert glucose to pyruvate is similar in all organisms. However, the fate of the pyruvate as it is used to generate energy is variable. As the process occurs, NAD* is reduced to NADH. The need for a continuous supply of NAD* for glycolysis is a key to understanding the fates of pyruvate.
- In each case, pyruvate is metabolized so as to regenerate NAD*, allowing glycolysis to continue.
There are 3 things that can happen to pyruvate after glycolysis 1. Oxidation to Acetyl-CoA under Aerobic conditions 2. Reduction to Lactate under Anaerobic conditions 3. Reduction to Ethanol under Anaerobic conditions for some prokaryotic organism (yeast ethyl alcohol) The normal case: pyruvateKrebs cycleETCoxidative phosphorylation = undergoing Aerobic (a lot of oxygen) Anaerobic = does not use oxygen/not enough oxygen
1. Oxidation to Acetyl CoA Under aerobic conditions (a plentiful supply of oxygen), pyruvate is oxidized in the mitochondria to form acetyl CoA:
- Most of the acetyl CoA formed can enter the citric acid cycle on its way to complete oxidation to CO 2.
- Some acetyl CoA serves as a starting material for fatty acid biosynthesis. NAD* is regenerated when NADH transfers its electrons to O 2 in the electron transport chain.
2. Reduction to Lactate Under anaerobic conditions (restricted Oz supply), such as those that accompany strenuous or long-term muscle activity , the cellular supply of oxygen is not adequate for the reoxidation of NADH to NAD*. Under these conditions, the cells begin reducing pyruvate to lactate as a means of regenerating NAD*.
Adding this equation to the net results of glycolysis produces the equation for lactate fermentation:
Cramps/Pulikat Napapagod yung muscle then magkakaroon ng build-up of lactic acid kaya nagkakaroon ng burning sensation sa certain area first aid: massage and cold compress to dissipate the pain then this would provide more energy to the cell
This reaction does not produce as much energy as the complete oxidation of pyruvate under aerobic conditions, but the two ATPs produced from lactate fermentation are sufficient to sustain the life of anaerobic microorganisms.
- In human metabolism, those two ATPs play a critical role by furnishing energy when cellular supplies of oxygen are insufficient for complete oxidation of pyruvate.
- During vigorous exercise, there is a shift to lactate production as a means for producing ATP; the
THE COMPLETE
OXIDATION OF GLUCOSE
Only 2 ATP is produced per mole of glucose by lactate fermentation and alcoholic fermentation. o Complete aerobic oxidation of glucose is thus 16 times more efficient than either of these processes The total energy available in glucose is:
ENERGY EFFICIENCY IN LIVING ORGANISMS
Thus, glucose oxidation liberates 686 kcal/mol, whereas the synthesis of 32 mol of ATP stores 234 kcal/mol. The efficiency of the energy storage is:
34 .1 % is used and a a lot of it is converted into heat coming from the bonds that are break and make
- Living cells can capture 34% of the released free energy and make it available to do biochemical work
- Automobile engines make available 20-30% of the energy actually released by burning gasoline.
ATP Calculations: SUMMARY
GLYCOGEN SYNTHESIS: GLYCOGENESIS
Excess glucose is converted into glycogen in a process called Glycogenesis. - Glycogen is stored primarily in the liver and muscle tissue, although some glycogenesis can occur in all cells. - The liver can store about 110 g of glycogen , and the muscles can store about 245 g. This anabolic process results in a bonding of glucose units to a growing glycogen chain. The energy is provided by the hydrolysis of uridine triphosphate (UTP; uracil + ribose + three phosphates).
Catabolic – breaking down Anabolic- building up
BREAKDOWN OF GLYCOGEN: GLYCOGENOLYSIS Glycogenolysis is the breakdown of glycogen back into glucose. - Happen during fasting - Glycogenolysis can occur in the liver (and kidney and intestinal cells) but not in muscle tissue because one essential enzyme (glucose 6- phosphatase) is missing. The first step in glycogen breakdown is the cleaving of the a(1-4) linkages , catalyzed by glycogen phosphorylase. Glucose units are released from the glycogen chain as glucose 1- phosphate:
A debranching enzyme hydrolyzes the a(1->6) linkages , eliminating the branches in glycogen. This allows the phosphorylase to continue acting on the rest of the chain In the second step, phosphoglucomutase isomerizes glucose 1- phosphate to glucose 6-phosphate: Glucose 1-Phosphate Glucose 6-Phosphate
In the final step, glucose 6-phosphate is hydrolyzed to free glucose by the enzyme glucose 6-phophatase (found only in liver, kidney, and intestinal cells): Glucose 6-Phosphate +H2o Glucose + Pi
GLYCOGEN IN MUSCLES AND THE LIVER Muscle cells lack glucose 6-phophatase and cannot form free glucose from glycogen. - They can carry out the first two steps of glycogenolysis to produce glucose 6- phosphate. - This form of glucose is the first intermediate in the glycolysis pathway, which produces energy. - Muscles therefore only use glycogen for energy production. In the liver , glycogen is broken down all the way to form free glucose , which is released into the blood during muscular activity and between meals.
Some are 30 ATP
- This glucose is used to maintain a relatively constant level of blood glucose.
GLUCONEOGENESIS The supply of glucose in the form of liver and muscle glycogen can be depleted by about 12- 18 hours of fasting , and in a shorter time as a result of heavy work or strenuous exercise. Nerve tissue, including the brain, would be deprived of glucose if the only source was glycogen. Gluconeogenesis is the process of synthesizing glucose from noncarbohydrate materials. When carbohydrate intake is low, and when glycogen stores are depleted, the carbon skeletons of lactate, glycerol (derived from the hydrolysis of fats), and certain amino acids are used to synthesize pyruvate , which is then converted to glucose : lactate, certain amino acids, glycerol pyruvate glucose
CORY CYCLE The Cori cycle is named in honor of Gerty Radnitz Cori (1896–1957) and Carl Cori (1896–1984) About 90% of gluconeogenesis occurs in the liver. - Very little takes place in the brain, skeletal muscle, or heart, even though these tissues have a high demand for glucose. - This allows the liver to maintain blood glucose levels so that tissues needing glucose can extract it from the blood. Gluconeogenesis involving lactate is especially important under anaerobic conditions. During exercise, lactate levels increase in muscle tissue, and some diffuses into the blood. This lactate is transported to the liver, where lactate dehydrogenase coverts it back into pyruvate
- The pyruvate is then converted to glucose by the gluconeogenesis pathway , and enters the blood.
- Thus, the liver increases a low blood glucose level and makes glucose available to the muscles.
- This cyclic process of transport of lactate from muscle to liver, the resynthesis of glucose by gluconeogenesis, and the return of glucose to muscle tissue is called the Cori cycle.
Summary of Major Pathways in Glucose Metabolism
- Glucose from food (carbohydrates)
- Glycolysis will be converted into C3 (Pyruvate)
- Pyruvate converted into Lactate in anerobic condition then regenerated back into Pyruvate via gluconeogenesis to form glucose
- Excess glucose = glycogen via glycogenesis
- Not eating= glycogen will be a fuel to form glucose via glycogenolysis
- Generally, all of this is highly regulated and some regulation is via enzymes but primarily we can control or regulate carbohydrates via hormones: Epinephrine, glucagon, insulin
REGULATION OF CARBOHYDRATE METABOLISM It is important that metabolic pathways be responsive to cellular conditions that that energy is not wasted in producing unneeded materials. Besides the regulation of enzymes at key control points, the body also uses three important regulatory hormones:
- epinephrine
- glucagon
- insulin INSULIN Insulin is a polypeptide hormone ( 51 A’As ) made in the b-cells of the pancreas. When carbohydrates are consumed, blood glucose levels rise, and the pancreas releases insulin into the bloodstream:
- This enhances the absorption of glucose from the blood into the cells of active tissues such as skeletal and heart muscles.
- Insulin also increases the rate of synthesis of glycogen, fatty acids, and proteins.
- Insulin stimulates glycolysis.
- As a result, blood glucose levels begin to decrease within one hour, and return to normal in three hours.
GLUCAGON Glucagon is a polypeptide hormone ( 29 A’As ) made in the a-cells of the pancreas.
- Glucagon activates the breakdown of glycogen in the liver , thereby increasing blood glucose levels, thus counteracting the effect of insulin.
- Insulin and glucagon work in opposition to each other, and blood sugar levels depend in part of the biochemical balance between these hormones.
- Activates glycogenolysis
EPINEPHRINE
Epinephrine (also known as adrenaline ) is a hormone and a neurotransmitter.
- It stimulates glycogen breakdown in muscles , and to a smaller extent in the liver.
- This glycogenolysis reaction provides energy for a sudden burst of muscular activity as a response to pain, anger, or fear (the "fight-or- flight" response )
- Epinephrine also increases heart rate, constricts blood vessels, and dilates air passages.
Carbohydrate Metabolism (LEC)
Course: BIOCHEMISTRY (CHM3)
University: Our Lady of Fatima University
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Students also viewed
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