Lecture 25: Metabolism and Energetics Lecturer: Dr. Barjis Room: P313 Phone: (718) 260-5285 E-Mail: ibarjis@citytech.cuny.edu

Learning Objectives Explain why cells need to synthesis new organic components Describe the basic steps in glycolysis, the TCA cycle, and the electron transport chain Summarize the energy yield of glycolysis and cellular respiration Describe the pathways involved in lipid, protein and nucleic acid metabolism

Learning Objectives Summarize the characteristics of the absorptive and postabsorptive metabolic states Explain what constitutes a balanced diet and why such a diet is important Define metabolic rate and discuss the factors involved in determining an individual’s BMR

Metabolism Cells break down organic molecules to generate energy (ATP) Energy is used for: growth, cell division, contraction, secretion, and other functions Metabolism is all the chemical reactions that occur in an organism Chemical reactions provide energy and maintain homeostasis: metabolic turnover growth and cell division special processes, such as secretion, contraction, and action potential propagation

An Introduction to Cellular Metabolism

Metabolism Metabolic reactions could be either catabolic (catabolism) or anabolic (anabolism) Anabolism Anabolism is the formation of new chemical bonds to produce new organic molecules New Organic molecules are needed for/to: Performance of structural maintenance and repairs Support of growth Production of secretions Building of nutrient reserves

Metabolism Catabolism Catabolism is the metabolic reactions that breaks down organic substrates in order to release energy Catabolic reactions occur in series of steps Catabolic reactions generate energy by breaking down large molecules to small molecule Small molecules enter Mitochondria to release more energy

Cells and Mitochondria Cells provide small organic molecules for their mitochondria Mitochondria produce ATP that is used by the cell to perform cellular functions i.e. cells feed mitochondria nutrient and in return mitochondria provide the cells with energy (ATP). Mitochondria accept only specific organic molecules e.g. Pyruvic Acid, acetyl coenzyme A Large organic nutrients (e.g. Glucose, fatty acid, amino acids) are broken down into smaller fragments (e.g. Pyruvic Acid) in the cytoplasm

Cells and Mitochondria Mitochondria breaks down the small fragments to carbon dioxide, water, and generates more energy (ATP) via two pathways: 1.  TCA cycle 2. Electron transport system (ETS)

Nutrient Use in Cellular Metabolism

Carbohydrate Metabolism Most cells generate ATP through the breakdown of carbohydrates Glycolysis is the process of breakdown of glucose into pyruvic acid Glycolysis occur in the cytoplasm and it requires: One molecule of glucose + 2 ATP + 4ADP + 2NAD + inorganic phosphate + cytoplasmic enzymes Glycolysis generates: Two pryruvic acid + 4ATP +2ADP + 2NADH The net gain of ATP of glycolysis is 2ATP (it produces 4ATP but two of the ATP are used)

Carbohydrate Metabolism Most cells generate ATP through the breakdown of carbohydrates Aerobic metabolism (cellular respiration) Pyruvic acid will enter mitochondria and generate more ATP via TCA cycle and ETS Two pyruvates = 34 ATP The chemical formula for this process is C6H12O6 + 6 O2  6 CO2 + 6 H2O Anaerobic metabolism (fermentation) In the absence of oxygen pyruvic acid will not enter mitochondria Pyruvic acid will go through the process of anaerobic respiration and will be converted into Lactic acid This process dose not generate any ATP

Glycolysis: Steps in Glycolysis Glucose (a 6 carbon molecule) enters the cell As soon as glucose is inside the cell, a phosphate is added to carbon number 6, and the new molecule is called glucose 6 phosphate. This reaction is called phosphorylation and it requires one ATP, enzyme called hexokinase. Glucose 6 phosphate goes through the second phosphorylation reaction and a phosphate is added to carbonenumber 1. The new molecule produced as a result is called Fructose 1,6 Bisphosphate The Fructose 1,6 bisphosphate (6 carbon molecule with phosphate s attached to carbon 1 and carbon 6) will split into two 3 carbon molecule: Glyceraldehyde 3 phosphate Dihydroxyacetone Each 3 carbon molecule will become a pyruvic acid through number of steps (see the diagram on the left)

Mitochondrial ATP Production (cellular respiration) The two pyruvic acid molecules will enter mitochondria In the mitochondria pyruvic acid will join Coenzyme A (CoA) to form acetyl CoA before entering the TCA cycle. TCA cycle will break down pyruvic acid completely Decarboxylation Hydrogen atoms passed to coenzymes Oxidative phosphorylation

The TCA Cycle Steps Pyruvic acid combine with coenzyme A to form acetyl coenzyme A. This reaction releases NADH and carbon dioxide Acetyl is a 2 carbon molecule. Acetyl-coenzyme A will give the two carbon molecule (acetyl) to the 4 carbon molecule (oxaloacetic acid) The 4 carbon molecule will become a 6 carbon molecule (citric acid) Citric acid will go through number of steps and will become back a 4 carbon molecule . The TCA cycle will begin with formation of citric acid and end with formation of oxaloacetic acid. The TCA cycle will run twice for one molecule of glucose, because one molecule of glucose produces two pyruvic acid and each pyruvic acid turns once cycle 7) Each cycle of TCA will generate 3NADH, 1FADH2, and 1GTP NADH and FADH2 will enter the electron transport system and generate ATP One NADH = 3ATP and one FADH2 = 2ATP (see ETS)

The TCA Cycle Pyruvic acid (a 3 carbon molecule) requires NAD and Coenzyme to form Acetyl coenzyme A This reaction will generate NADH, carbon dioxide and acetyl coenzyme A. Notice that pyruvic acid is a 3 carbon molecule , in this reaction one of the carbons was released as carbon dioxide is formed and two carbon is left as a acetyl Acetyl coenzyme A will transfer the acetyl to oxaloacetic (a 4 carbon molecule) acid and coenzyme A will becomee free. 4 carbon molecule from oxaloacetic acid and two carbon from acetyl will generate a 6 carbon molecule (citric acid) The free coenzyme A will be reused by another pyruvic acid. Citric acid will go through number of steps (e.g. it will become isocetric acid then ketoglutaric acid and so on)and eventually will become oxaloacetic acid

The TCA Cycle The free coenzyme A will be reused by another pyruvic acid. Citric acid will go through number of steps (e.g. it will become isocetric acid then ketoglutaric acid and so on)and eventually will become oxaloacetic acid

Oxidative phosphorylation and the ETS Requires coenzymes and consumes oxygen Key reactions take place in the electron transport system (ETS) Cytochromes of the ETS pass electrons to oxygen, forming water The basic chemical reaction is: 2 H2 + O2  2 H2O

Electron Transport System (ETS) ETS is sequence of proteins called cytochromes Each cytochrome has: A protein - embedded in the inner membrane of a mitochondrion, A pigment

STEP1: coenzyme strips a pair of hydrogen atoms from a substrate molecule. STEP2: NADH and FADH2 deliver hydrogen atoms to coenzymes embedded in the inner membrane of a mitochondrion. STEP3: Coenzyme Q accepts hydrogen atoms from FMNH2 and FADH2 and passes electrons to cytochrome b. STEP4: Electrons are passed along the electron transport system, losing energy in a series of small steps. The sequence is cytochrome b to c to a to a3. STEP5: At the end of the ETS, an oxygen atom accepts the electrons, creating an oxygen ion (O–). This ion has a very strong affinity for hydrogen ions (H+); water is produced.

Oxidative Phosphorylation

Energy yield of glycolysis and cellular respiration Per molecule of glucose entering these pathways Glycolysis – has a net yield of 2 ATP Electron transport system – yields approximately 28 molecules of ATP TCA cycle – yields 2 molecules of ATP

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

A Summary of the Energy Yield of Aerobic Metabolism

Synthesis of glucose and glycogen Gluconeogenesis Synthesis of glucose from noncarbohydrate precursors such as lactic acid, glycerol, amino acids Liver cells synthesis glucose when carbohydrates are depleted Glycogenesis Formation of glycogen Glucose stored in liver and skeletal muscle as glycogen Important energy reserve

Carbohydrate Breakdown and Synthesis

Lipid catabolism Lipolysis Lipids broken down into pieces that can be converted into pyruvate For example triglycerides are split into glycerol and fatty acids Glycerol enters glycolytic pathways Fatty acids enter the mitochondrion

Lipid catabolism Beta-oxidation Breakdown of fatty acid molecules into 2-carbon fragments Lipids and energy production Used when glucose reserves are limited

Beta Oxidation In beta oxidation long chain of fatty acids are broken down into fragments of two carbons. Say we have a fatty acid chain that is 18 carbon long. During beta oxidation fragments of two carbon will be removed from the chain of fatty acid. So after the first round of reaction (as shown in the figure) a fatty acid chain that is 16 carbon long will remain, after the second round of reactions a fatty acid chain that 14 carbon long will remain For each round of reaction two carbon will be removed from the chain. As two carbons are removed from the chain, NADH, FADH2 and Acetyl CoA will be generated. The steps in beta oxidation: Coenzyme A bind to fatty acid. This step requires one ATP 2) This reaction will prepare fatty acid for beta oxidation and generate a fatty acid attached to CoA

Beta Oxidation 3) The first round of beta oxidation will generate one NADH, one FADH2 and one Acetyl CoA 4) Acetyl CoA will enter TCA cycle and generate 3NADH, 1FADH and 1GTP. 3NADH = 9ATP, 1FADH2 = 2ATP, and GTP = 1ATP.

Beta Oxidation NADH and FADH2 will enter the ETS and generate ATP 1NADH = 3ATP 1FADH2 = 2ATP Summary : one round of beta oxidation will generate : NADH = 3ATP FADH2 = 2ATP Acetyl CoA = 12ATP So if each round of beta oxidation produces 17ATP, then one molecule of fat will produce a lot more ATP (energy) than one molecule of glucose. Remember that glucose produced 2ATP in glycolysis and 34/36ATP via TCA and ETS

Lipid synthesis (lipogenesis) Non essential fatty acids are the fatty acids that can be synthesized Essential fatty acids are fatty acid that cannot be synthesized and must be included in diet Example of essential fatty acids include: Linoleic and linolenic acid

Lipid Synthesis

Lipid transport and distribution Lipoproteins are lipid-protein complex that contains large glycerides and cholesterol 5 types of lipoprotein 1) Chylomicrons Largest lipoproteins composed primarily of triglycerides Delivers lipids from digestive tract (intestine) to liver 2) Very low-density lipoproteins (VLDLs) Contain triglycerides, phospholipids and cholesterol Delivers triglycerides to the cells Lipoprotein lipase (enzyme) in the capillaries break the triglyceride into monoglyceride and fatty acid for use by the cell Steps: VLDL containing triglyceride is released into blood circulation by the liver When VLDL gets to the capillaries, an enzyme called lipase break the triglycerides into monglyceride and free fatty acid The monoglyceride and free fatty acid are used by the cell VLDL is left with less triglyceride so it is called IDL

Lipid transport and distribution 3) Intermediate-density lipoproteins (IDLs) Contain smaller amounts of triglycerides Return remaining triglycerides back to the liver When the IDL arrives into the liver, the livers adds cholesterol to IDL. Once cholesterol is added to the IDL, it would be called LDL 4) Low-density lipoproteins (LDLs) – also called the bad cholesterol Contain mostly cholesterol LDL is released into the blood stream by the liver LDL delivers cholesterol to the cells The cell uses the cholesterol for synthesis of membrane, hormones and other material Any excess cholesterol that is not used by the cell will diffuse out of cell back into capillaries (circulation) 5) High-density lipoproteins (HDLs) also called the good cholesterol HDL collects the extra cholesterol that diffuses out of the cell and delivers them back to the liver The liver reuses the cholesterol to make LDL, and excretes any excess cholesterol with bile

Lipid Transport and Utilization

Lipid Transport and Utilization

Protein Metabolism Amino acid catabolism If other sources inadequate, mitochondria can break down amino acids TCA cycle The first step in amino acid catabolism is the removal of the amino group (-NH2) The amino group is removed by transamination or deamination Transamination – attaches removed amino group to a keto acid Deamination – removes amino group generating NH4+ Proteins are an impractical source of ATP production

Amino Acid Catabolism: Transamination Attaches the amino group of an amino acid to a keto acid   Transamination converts the keto acid into an amino acid that can enter the cytosol and be used for protein synthesis Reactions enable a cell to synthesize many of the amino acids needed for protein synthesis  

Amino Acid Catabolism: Deamination Deamination preparing an amino acid for breakdown in the TCA cycle Deamination removes an amino group of an amino acid and enerates an ammonia (NH3) molecule or an ammonium ion (NH4+). Ammonia molecules are highly , thus liver (the primary site of deamination) has enzymes that converts the ammonia to urea

Amino Acid Catabolism

Protein synthesis Essential amino acids Cannot be synthesized by the body in adequate supply Nonessential amino acids Can be synthesized by the body via amination Addition of the amino group to a carbon framework

Nucleic acid metabolism Nuclear DNA is never catabolized for energy RNA catabolism RNA molecules are routinely broken down and replaced Generally recycled as nucleic acids Can be catabolized to simple sugars and nitrogenous bases Do not contribute significantly to energy reserves

Body has five metabolic components Liver The focal point for metabolic regulation and control Adipose tissue Stores lipids primarily as triglycerides Skeletal muscle Substantial glycogen reserves

Body has five metabolic components Neural tissue Must be supplied with a reliable supply of glucose Other peripheral tissues Able to metabolize substrates under endocrine control

Vitamins Are needed in very small amounts for a variety of vital body activities Fat soluble Vitamins A, D, E, K Taken in excess can lead to hypervitaminosis Water soluble Not stored in the body Lack of adequate dietary intake = avitaminosis

You should now be familiar with: Why cells need to synthesis new organic components The basic steps in glycolysis, the TCA cycle, and the electron transport chain The energy yield of glycolysis and cellular respiration The pathways involved in lipid, protein and nucleic acid metabolismBMR

You should now be familiar with: The characteristics of the absorptive and postabsorptive metabolic states What constitutes a balanced diet and why such a diet is important Metabolic rate and the factors involved in determining an individual’s BMR