Unit B - Energy Transformation

Biochemistry

A1:

1. Given a molecular structure, classify it as an aldose, ketose or non-carbohydrate.

2. Given a carbohydrate structure, identify the anomeric carbon(s).

3. Given a disaccharide, oligosaccharide or polysaccharide structure, identify glycosidic linkages.

4. Given a monosaccharide, disaccharide, oligosaccharide, or polysaccharide structure, identify the reactive (reducing) end(s) of the molecule and location(s) of glycosidic linkage(s).

5. Given a carbohydrate covalently bonded to another biomolecule (e.g., phosphoryl group, protein, lipid) discriminate between glycosidic and non-glycosidic linkages.

6. Given the structure of glycogen, discriminate between components synthesized by glycogenin, glycogen synthase and branching enzyme.

7. Given the structure of glycogen, summarize its chemical and physical properties that make it a safe and efficient way of storing energy in cells.

Carbohydrates

Carbon-based molecules that are rich in hydroxyl groups (CH₂O)_n

• “Polyhydroxy aldehydes and ketones and their derivatives”

Carbonyl Group

A functional group with a carbon atom double-bonded to an oxygen atom, found in aldehydes and ketones.

Aldehyde

A type of organic compound containing a carbonyl group located at the end of the carbon chain, characterized by the formula RCHO.

Ketone

An organic compound containing a carbonyl group located within the carbon chain, characterized by the formula RC(=O)R'.

Monosaccharides

Commonly Known as Sugars used for DNA and fuel molecules

• 3 to 7 carbons in length

Monosaccharides are Classified by :

by carbon-chain length and identity of most oxidized group

Constitutional Isomers

identical molecular formulas but differ in how the atoms are ordered

Stereoisomers

Atoms are connected in the same order but differ in spatial arrangement

• compounds with the same formula and connectivity but different 3D spatial arrangements.

• 2^{n - where n is the number of chiral centers}

Diastereomers

A specific type of stereoisomer that are not mirror images of each other and are not superimposable

Anomers

A type of cyclic sugar isomer that differs from another isomer at the anomeric carbon, resulting in different configurations.

alpha Haworth projections

hydroxyl groups attached to C-1 below the plane of the ring

beta Haworth projections

hydroxyl groups attached to C-1 above the plane of the ring

Anomeric Carbon

It is a chiral carbon atom in a cyclical sugar characterized by being bonded to two oxygen atoms—the ring oxygen and a hydroxyl group—allowing for two configurations: (trans) and (cis).

Axial bonds

perpendicular to the plane of the ring can cause steric hindrance if on the same side of the ring

Equatorial Bonds

parallel to the plane of the ring and generally less sterically hindered compared to axial bonds, this causes more stable conformations in cyclic structures.

What conformation is the most stable

Chair conformation with (-OH and CH2OH) in the equatorial positions to minimize steric strain

Glucose is a Reducing Sugar

because it has a free aldehyde or ketone group that can donate electrons, enabling it to reduce other compounds

• in its open-chain form) or a free hemiacetal group (in its cyclic form), allowing it to reduce oxidizing agents like Cu+

Glycation

Reducing sugars can often nonspecifically react with a free amino group, usually at alysine or arginine residue, to form a stable covalent bond.

This process can lead to the formation of advanced glycation end products (AGEs), which are implicated in various diseases.

Glycosidic linkage

is a type of covalent bond that joins a carbohydrate (sugar) molecule to another group, which can be another sugar or a different molecule. These linkages are formed through a dehydration reaction, involving the removal of a water molecule.

O-Glycosidic linkage

are prominent when carbohydrates are joined together to form long polymers

Oligosaccharides

two or more monosaccharides by O-glycosidic linkages

• Directionality defined by their reducing and nonreducing end

Glycosidic Linkage

between the a-anomeric form of C-1 on one sugar and the hydroxyl oxygen atom on C-4 of the adjacent sugar.

• This type of linkage can be classified as alpha or beta based on the orientation of the anomeric carbon.

Reducing End for Oligosaccharide

refers to the end of an oligosaccharide that has a free anomeric carbon capable of acting as a reducing agent in chemical reactions.

• By convention, this end of the oligosaccharide is still called the reducing end even when it is bound to another molecule such as a protein and thus no longer has reducing properties.

Disaccharides

are carbohydrates formed from two monosaccharides linked by a O-glycosidic bond.

Polysaccharides

are carbohydrates composed of long chains of monosaccharide units connected by glycosidic bonds, serving various functions such as energy storage and structural support.

• Such as Glycogen and Starch

Glycogen

is a polysaccharide that serves as a form of energy storage in animals, composed of glucose units bonded together.

• Most Abundant in skeletal muscle and liver but most tissues have glycogen

Intramolecular Hemiacetal

C-1 aldehyde in the open-chain form of glucose reacts with the C-5 hydroxyl group to form a cyclic structure.

The open-chain form of glucose cyclizes when the C-5 hydroxyl group attacks the C-1 carbon of the aldehyde group to form an intramolecular hemiacetal. Two interchanging anomeric forms of the pyranose ring, designated α and β can result, both in rapid equilibrium with the open-chain (linear) form.

Glycosyltransferases

catalyze the formation of glycosidic linkages between monosaccharides in carbohydrate synthesis.

Glycogen

A polysaccharide used for energy storage in animals, primarily found in muscles and liver.

alpha Glycosidic linkages

form open helical polymers

• commonly form open, flexible helical, coiled structures. These linkages are characterized by the oxygen atom at the anomeric carbon (C1) pointing downward (below the ring plane) in the

  -D-glucose monomers

beta Glycosidic linkages

produce nearly straight strands that can form rigid structures

• . These linkages are characterized by the oxygen atom at the anomeric carbon (C1) pointing upward (above the ring plane) in the -D-glucose monomers.

Glycogen Degradation:

Glucose 6-phosphate has three possible fates

(1) it can be metabolized by glycolysis;

(2) in the liver it can be converted into free glucose for release into the bloodstream;

(3) it can be processed by the pentose phosphate pathway

Glycogen Phosphorylase

cleaves its substrate by the addition of orthophosphate (Pi) to yield glucose 1-phosphate. The cleavage of a covalent bond by the addition of orthophosphate is referred to as phosphorolysis:

Debranching enzyme

is responsible for removing a glucose unit from the branching points of glycogen. It acts on both alpha-1,6-glucosidic bonds, which allows for the complete mobilization of glucose units during glycogen degradation.

Glycogen synthase

is the key regulatory enzyme responsible for synthesizing glycogen from glucose, joining glucose molecules through alpha-1,4-glycosidic bonds, and plays a crucial role in glycogen storage.

Steps of Glycogen Synthesis Occurs?

• Glycogen synthesis requires a primer such as Glycogenin

• Glucose Units are added stepwise using UDP-glucose as the donor

• Glucosyl residues are joined in alpha-1,4-linkages to extend the glycogen chain, while branch points are formed by alpha-1,6-linkages.

• Branching enzymes introduce alpha-1,6-linkages to create branches, enhancing the solubility and accessibility of the glycogen molecule.

• Branching Increases the rate of glycogen synthesis and degradation

Uridine diphosphate glucose

is a vital activated nucleotide sugar () that serves as a key glycosyl donor in metabolism. It is a precursor for glycogen, glycolipids, and glycoprotein synthesis. It is synthesized from glucose-1-phosphate and uridine triphosphate (UTP)

Glycogen Synthase exist in two forms :

nonphosphorylated alpha form

usually inactive phosphorylated beta form - when glycogen synthesis is not needed, though it can be partially activated by high concentrations of glucose-6-phosphate.

B2:

1. Given the structure of ATP, summarize the thermodynamic and chemical basis for its suitability as the energy currency of the cell.

2. Given an enzyme-coupled reaction involving the utilization of ATP, summarize the principles that promote catalysis of an otherwise thermodynamically unfavorable reaction.

3. Given an enzyme-coupled reaction other than those involving ATP, identify the activated carrier and its high energy transfer potential group that operates under similar kinetic and thermodynamic principles as ATP.

4. Given information about the physiological status of a cell or tissue, demonstrate the concept of energy charge to predict changes in the adenine nucleotide pool and resultant anabolic or catabolic state of that cell or tissue.

Three reasons for continual input of free energy:

(1) mechanical work in muscle contraction and cellular movements,

(2) the active transport of molecules and ions

(3) the synthesis of macromolecules and other biomolecules from simple precursors.

Phototrophs

organisms that obtain energy from light.

Chemotrophs

organisms that obtain energy from chemical compounds.

Unifying themes to all metabolic reactions :

• Metabolism is a coherent network containing many common motifs. - ATP is the primary energy currency, driving biochemical processes.

• While metabolism involves many different reactions, it uses only a few kinds of mechanisms

• Metabolic reactions are highly regulated.and are interconnected through various pathways.

Metabolic Pathways into broad classes :

1. Those that convert energy form fuels into biologically useful forms

2. Those who require inputs of energy to proceed

Catabolic reactions

processes that break down molecules to release energy

• Example oxidation of carbs and fat in human to make ATP and waste products CO2 and H2O

Anabolic Reactions

processes that build up molecules, requiring energy input.

• Examples include DNA, protein synthesis and glucose formation.

Amphibolic Pathways

pathways that can function in both anabolic and catabolic processes, depending on the energy conditions in the cell

Pathways Must Have Two Criteria :

1. Individual reactions must be specific

2. Each of the reactions that constitutes the pathway must be thermodynamically favored under real, rather than standard, conditions. A reaction that is specific yields only one particular product or set of products from its reactants

In a metabolic pathway, reactions with a positive ΔG°′ :

• Can Proceed under physiological conditions because the concentrations of reactants and products are far from standard conditions, such that the ΔG of the reaction is negative

• Adding other reaction that have - ΔG can help drive the overall pathway forward, allowing cellular processes to occur.

• Thermodynamically unfavorable reactions can be driven by a thermodynamically favorable reaction to which it is coupled

ATP

Energy-rich molecule because its triphosphate unit contains two phosphoanhydride linkage

• Adenine, Ribose, Triphosphate Unit

ATP releases energy when converting to ADP

Because it breaks a high-energy phosphate bond, relieving electrostatic repulsion between negatively charged phosphate groups

ADP

B3:

1. Given the  and the  values of the reactions of glycolysis, determine if they are metabolically reversible or irreversible.

2. Given metabolites of glycolysis or the products of pyruvate catabolism, define their oxidation states.

3. Given the ATP-synthesizing steps of glycolysis, summarize the thermodynamic rationale for ATP production from glycolytic intermediates with high phosphoryl-transfer potential.

4. Given defined biochemical or physiological conditions, discriminate between the aerobic or anaerobic fate of pyruvate.

• Ch 16.1: Glycolysis is an energy-conversion pathway in most organisms

• Ch 16.2: NAD+ is generated from the metabolism of pyruvate

• Ch 18.1: Pyruvate dehydrogenase forms acetyl coenzyme A from pyruvate

Glycolysis

a sequence of reactions that break down (metabolize) one molecule of glucose → two molecules of pyruvate, producing a net production of ATP

• Does not require oxygen (anaerobic)

• Occurs in Prokaryotic and Eukaryotic

In aerobic conditions pyruvate can

can by completely oxidized to CO₂, generating much more ATP

Glucose is the most common fuel for almost all organisms:

• It could have been available for prehistoric conditions

• Most stable hexose because of the hydroxyl groups and hydroxymethyl group in equatorial position and minimizing steric clashes

• Stability allows for efficient energy extraction during glycolysis and cellular respiration, making it the primary energy source for cellular functions.