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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry THE CHEMISTRY IN BIOCHEMISTRY • Metabolism can be summarized in the overall scheme given below:
Ø Matter is conserved & Energy is conserved • To understand cellular metabolism, we need to discuss how different functional groups chemically react with each other
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry FUNCTIONAL GROUPS IN BIOCHEMICAL REACTIONS • The field of biochemistry classifies reactions based on the chemical behavior of specific functional groups • Each organic functional group we studied is associated with one or more characteristic biochemical reactions
• You should know these!
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry CLASSES OF BIOCHEMICAL REACTIONS • There are six basic chemical reactions that describe the bulk of biochemistry: 1. Oxidation-reduction reactions
2. Hydration-dehydration reactions Chapter 10 3. Acyl group transfer reactions Material 4. Phosphoryl group transfer reactions
5. Decarboxylation reactions Covered later 6. Reactions that form or break in metabolism carbon-carbon bonds lectures
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry OUTLINE • 10.1 The Role of Functional Groups in Biochemical Reactions
• 10.2 Oxidation-Reduction Reactions
• 10.3 Hydration/Dehydration Reactions
• 10.4 Acyl group transfer reactions
• 10.5 Phosphoryl group transfer reactions
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry
OXIDATION-REDUCTION REACTIONS • Oxidation-reduction (aka. “Redox”) reactions always involve a transfer of electrons. • There are four specific sub-classes of redox reactions we will consider: 1. Metal/nonmetal reactions 2. Combustion reactions 3. Hydrocarbon redox reactions involving C-C bonds 4. Redox reactions involving C-O bond containing functional groups
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry DEFINITION OF OXIDATION-REDUCTION REACTIONS • Redox reactions occur when an electron is transferred between two reactants: Ø The reactant that loses an electron is being oxidized Ø The reactant that gains the electron is being reduced
• Remember it this way: The reactant that is being “reduced” is getting a reduction in charge
• Note that both reactions must occur at the same time (one reactant is reduced, the other oxidized)
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry AN EXAMPLE OF REDOX REACTIONS
Mg(s) + 2HCl(aq) à H2 (g) + MgCl2(aq) • In this reaction, 2 electrons are donated (or lost) by the Mg, so it is oxidized: Mg à Mg2+ + 2e- • Two H+ receive (or gain) the electrons to form hydrogen gas, so they become reduced: + - 2H + 2e à H2 • The chloride (Cl-) ion remains unchanged; it is called a “spectator ion”
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry METAL-NONMETAL REDOX REACTIONS • In general, metals and non-metals exchange electrons in redox reactions. Ø Whenever a cation forms from a metal, it has undergone an oxidation (neutral à (+) positive)
Ø Whenever an anion forms from a nonmetal, it has undergone a reduction (neutral à (-) negative)
• Iron rusting in oxygen is a common redox reaction:
4 Fe + 3 O2 à 2 Fe2O3
Iron is Oxygen is Fe3+ O2- oxidized reduced
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry COMBUSTIONS ARE REDOX REACTIONS • Reaction of methane (natural gas) with oxygen is a typical combustion reaction:
CH4(g) + 2O2 (g) à CO2(g) + 2H2O(g) • In this reaction, electrons are transferred from the methane to the oxygen Ø Methane is oxidized (nonpolar C-H bonds broken) Ø Oxygen is reduced (nonpolar O=O bonds broken) Ø New polar C=O and O-H bonds form • Organic compounds in the cell are oxidized in a similar way to generate energy during “cellular respiration”
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry HOW TO TELL WHEN ORGANIC COMPOUNDS UNDERGO REDOX REACTIONS • The redox reactions of organic molecules involve changes to bond structure (“partial” e- transfer) 1. The number of polar bonds to carbons increases and the number of non-polar bonds to carbons decreases 2. The more electronegative atom is reduced, while the less electronegative atom is oxidized
glucose CH4(g) + 2O2 (g) à CO2(g) + 2H2O(g)
methane oxygen
C6H12O6(s) + 6O2 (g) à 6CO2(g) + 6H2O(g)
General, Organic, and Biochemistry Chapter 10: Figure 10.3 REDOX REACTIONS DRIVE CONVERSIONS BETWEEN FUNCTIONAL GROUPS • Oxygen containing Redox Conversion Reactions functional groups are at different levels of oxidation: alcohol
oxidation carboxylic acid
• Oxidation of different alcohols results in distinct functional groups formation
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry HYDROCARBON REDOX REACTIONS • Changes to C-C bonds are also redox reactions • Less saturated carbons are more oxidized:
oxidation reduction oxidation alkane à alkene à alkyne
• The overall energy per bond changes in single vs. double vs. triple C-C bonds
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry CATALYTIC HYDROGENATION • The food industry uses catalytic hydrogenation to reduce liquid plant oils (alkenes) into solids such as margarine (mostly alkanes): Ø High heat and a metal catalyst (Pt or Pd) is used
Ø The reducing agent is hydrogen gas (H2)
catalytic hydrogenation reactions
Alkene Alkane
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry A PROBLEM WITH HYDROGENATIONS • Industrial hydrogenation of oils is not always a complete process….some C=C bonds remain: Ø The naturally occurring C=C bonds found in plant oils are all cis-double bonds
Ø “Partial hydrogenation” of cis C=C bonds results in the production of trans C=C bonds
• Trans-fats are associated with increased risk for obesity and cardiovascular disease.
http://bio1151b.nicerweb.net/Locked/media/ch05/05_fatty-acids2.gif
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry PRACTICE PROBLEM Determine whether the following reactions represent an oxidation or a reduction of the organic substance shown.
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry ENZYMATIC REDOX REACTIONS • All redox reactions require an oxidant AND reductant for the electron transfer to occur: Ø Reactants receiving the electrons from a molecule undergoing oxidation are called oxidizing agents Ø Reactants providing electrons to molecules undergoing reductions are called reducing agents
• Biochemical redox reactions involving enzymes often use coenzymes to serve as electron carriers Ø Coenzymes can accept electrons during catabolism Ø Coenzymes can donate electrons during anabolism
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry VITAMINS AND HEALTH • Vitamin deficiency results in a number of diseases. • Two classes of vitamins: Ø Water soluble: B complex and C Ø Fat soluble: A, D, E, and K • Several of the water soluble vitamins are used to form important Coenzymes.
General, Organic, and Biochemistry Chapter 10: Figure 10.9 B-VITAMINS USED AS COENZYMES
vitamin B 3 NAD+ (oxidized form) Niacin
vitamin B2 FAD (oxidized form)
Riboflavin
vitamin B5 Coenzyme A Pantothenic acid (CoA)
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry THE COENZYME NAD+/NADH • In biochemical systems, the coenzyme NAD+ is commonly used (with an enzyme) to oxidize oxygen containing functional groups:
NAD+ (oxidized form)
NADH (reduced form)
1°Alcohol Aldehyde (reduced) (oxidized)
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry OXIDATION OF ALCOHOLS • The oxidation of alcohols is a two-step process that involves the NAD+ coenzyme:
1° alcohols à aldehydes à carboxylic acids
1. The coenzyme NAD+ is the oxidant that removes both electrons and protons from ethanol & acetaldehyde 2. The catalysts driving each step are enzymes
2e- 2e-
+ + NAD NADH NAD NADH + H+ + H+
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry PRACTICE PROBLEM Predict what product forms in the following reactions:
+ NAD+ à
+ NADH à
ß NADH + + NAD+ à
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry
THE COENZYME FAD/FADH2 • In biochemical systems, the coenzyme FAD is commonly used (with an enzyme) to oxidize C-C bonds in hydrocarbons:
FADH FAD 2 (reduced form) (oxidized form)
Alkane Alkene (reduced) (oxidized)
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry ANTIOXIDANTS ARE ELECTRON SCAVENGERS • An antioxidant is a compound that prevents harmful oxidation of important substances in the cell because it is an effective reducing agent. What sort of functional groups on antioxidants would you expect to mediate their “electron scavenging” function?
glutathione ascorbic acid (vitamin C)
a-tocopherol (vitamin E)
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry HYDRATION REACTIONS • In a hydration reaction, water is added to an alkene, replacing the double bond: Ø The water is split: –OH and –H are singly bonded to the two carbons from the original alkene C=C bond • In biochemical systems, this occurs mostly when the alkene is adjacent to a carbonyl group
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry DEHYDRATION REACTIONS • Dehydration reactions are simply the reverse of hydration reactions: Ø A water is removed from an alcohol to form an alkene Ø Removal of the alcohol is a reduction reaction • These also commonly occur adjacent to a carbonyl group in biochemical systems
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry EXAMPLE OF BIOCHEMICAL HYDRATION
• The catabolism of fatty acids (b-oxidation) has a step that involves the formation of an alcohol from an alkene:
• Note the position of the carbonyl in this example: What is the functional group involved here?
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry PRACTICE PROBLEMS One important biochemical pathway (the citric acid cycle) involves the reaction shown.
1. How can you quickly determine that this reaction is a hydration or dehydration reaction?
2. Where are the two carbonyl groups in this reaction?
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry THE ACYL GROUP • The acyl group is common in biomolecules: Ø Acyl = a hydrocarbon that ends in a carbonyl
Acyl group
• Acyl groups come in many forms: Ø The atom next to the carbonyl carbon determines the identity of the acyl group
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry DIFFERENT CLASSES OF ACYL GROUP TRANSFER REACTIONS • Acyl group transfer reactions involve transfer of the acyl group from one functional group to another • Most involve transfer of an acyl between a carboxylic acid and one of the other functional groups Ø Example: formation of triglycerides from fatty acids
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry HYDROLYSIS REACTIONS • A hydrolysis reaction involves the use of a water molecule to break a bond: Ø “hydro” = water + “lysis” = to break open Ø Hydrolysis is a common catabolic reaction used to break down complex molecules into simpler ones • A condensation reaction is the reverse of a hydrolysis Don’t confuse these with hydration/dehydration reactions….. …..they are different! ethanoic methanol methyl acid ethanoate water
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry HYDROLYSIS OF ACYL GROUPS • A common example of hydrolysis reactions is the removal of an acyl group from an ester, thioester, or amide: Ø Similar to a hydration reaction, except the water molecule is added to the carbonyl carbon (not an alkene) Ø The resulting products are a carboxylic acid + another functional group
Know how to predict the specific products of acyl group hydrolysis
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry HYDROLYSIS OF AMIDES IN PROTEINS • Amides are found in proteins and their hydrolysis is the first stage of protein catabolism: Ø The amide bond in a protein is called a peptide bond
Ø Amide hydrolysis produces amines and carboxylic acids • The final product of protein catabolism is individual amino acids
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry SOAP FROM FAT • Soap can be made by hydrolysis of fats: Ø This process is also called saponification Ø Requires a strong base (NaOH) and heating in the presence of water • Products are glycerol and fatty acids (in carboxylate salt form), which we call “soaps”
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry ESTERIFICATION REACTIONS • In an esterification reaction, an alcohol and a carboxylic acid react to form an ester: Ø Esterification is a specific kind of condensation reaction (water is produced)
Ø This is simply the reverse reaction of ester hydrolysis esterification (condensation)
saponification (hydrolysis)
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry EXAMPLES OF ESTERS
Many esters are the characteristic flavors and fragrances associated with fruits and perfumes.
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry THIOESTERS • When a sulfur replaces an oxygen in alcohols, the resulting compound is called a thiol.
Thiol
• Condensation of a carboxylic acid with a thiol results in a thioester. Ø The thioester acetyl CoA has many important biochemical roles.
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry PRACTICE PROBLEMS 1. What products would results from the following esterification reactions?
1. What is the meaning of the curved arrow in the next example? What is the product?
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry PHOSPHORYL GROUPS • Phosphoryl groups consist of a central phosphorus surrounded by three oxygen atoms. Ø Two of the oxygens are joined by single bonds and the third is joined by a double bond to the phosphorus. Ø A fourth oxygen atom joins the phosphoryl group to a carbon atom (P-O-R), which is a phosphate ester
Phosphate esters are highly significant in biochemistry, as these bonds carry significant charge and energy
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry TRANSFERRING PHOSPHORYL GROUPS • In phosphoryl group transfer reactions, the phosphoryl group moves between two molecules. Ø These reactions are central to biochemistry due to their role in energy transfer. • A series of phosphoryl groups linked in tandem is common in energy carrying molecules like ATP
Ø The bond connecting multiple phosphoryl groups is called a phosphoanhydride bond
Adenosine Triphosphate (ATP)
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry HYDROLYSIS OF PHOSPHOANHYDRIDES • Phosphoryl group transfer reactions are very similar to simple hydrolysis of a phosphoryl group Ø Hydrolysis of a phosphoryl produces the “inorganic phosphate” molecule (Pi)
• Phosphoryl group transfer usually occurs by replacing a phosphoanhydride bond with a new phosphate ester bond: Ø The functional group involved is an alchol –OH Ø Recall chemistry of alcohols is similar to water
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry EXAMPLE OF PHOSPHORYL TRANSFER • In the first stage of glucose catabolism, a phosphoryl group is transferred: Ø The phosporyl donor is ATP Ø The phosphoryl acceptor is an alcohol on glucose
alcohol
ATP phosphoryl glucose
glucose-6- phosphate
ADP
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry CELLULAR ENERGY TRANSFER • Phosphoryl group transfer reactions involving phosphoryl groups from ATP may transfer energy: Ø The phosphoanhydride bond is often called a “high energy bond.” (recall the “spring”) analogy • ATP is the main “storage depot” for transferring chemical energy in the cell: Ø Energy released through the catabolism of fats and carbohydrates may be used to transfer a phosphoryl group to ADP forming ATP. Ø Energy released when the phosphoanhydride in ATP is hydrolyzed can be transferred to other biochemical reactions to do work or drive anabolic reactions
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry PRACTICE PROBLEM 1. Explain why the reaction shown below is classified as a phosphoryl group transfer reaction.
2-phosphoglycerate glycerate
1. In the reaction shown below, to which part of the molecule would you expect a phosphoryl to be transferred?
mevalonate
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry SUMMARY OF BIOCHEMICAL REACTIONS
CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry SUMMARY REACTION DESCRIPTIONS • Overview of Functional Groups and Biochemical Reactions Ø Chemical reactions can be classified according to the functional group transformations that occur. 1. Oxidation-Reduction Reactions Ø Electrons are transferred between reactants in an oxidation- reduction reaction. • Oxidation is the loss of electrons. • Reduction is the gain of electrons. Ø In organic molecules, oxidation appears as an increase in oxygen atoms and/or a decrease in hydrogen atoms; and reduction appears as the reverse. 2. Hydration/Dehydration Reactions Ø In a hydration reaction, an OH group and an H atom are added to a double bond. Ø In a dehydration reaction, an OH group and an H atom are lost as water, leaving a double bond in their place.
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CHAPTER 10: Reactions of Organic Functional Groups in Biochemistry SUMMARY REACTION DESCRIPTIONS 3. Hydrolysis & Condensation Reactions Ø Acyl group transfer reactions convert carboxylic acids into their derivatives: esters, thioesters, and amides, and vice versa. Ø The conversions between these functional groups involve water in hydrolysis & condensation reactions. Ø Esters, thioesters, and amides react with water in hydrolysis reactions to produce a carboxylic acid and either an alcohol, a thiol, or an amine, respectively. Ø When carboxylic acids react with an alcohol, a thiol, or an amine in a condensation reaction, water is produced along with an ester, thioester or amide, respectively. 4. Phosphoryl Group Transfer Reactions Ø The phosphoryl group is usually transferred between the oxygen atom of water, alcohols, carboxylic acids, or other phosphates. Ø The phosphoanhydride bond joins phosphoryl groups in molecules like ADP and ATP. Ø The phosphoanydride bond is a high energy bond that releases energy upon hydrolysis.
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