Metabolism - StFX · Cells take up the products of digestion • Human diet consists of four types of biomolecules – Proteins – Nucleic acids – Polysaccharides

Lecture Notes for

Chapter 12/13/14/15/16/17 Metabolism

Essential Biochemistry

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.

Overview of Metabolism

Breaking down molecules

Building up molecules

Free energy comes from hydrolysis of ATP

© 2014 John Wiley & Sons, Inc. All rights reserved.

Cells take up the products of digestion.

•  Human diet consists of four types of biomolecules –  Proteins –  Nucleic acids –  Polysaccharides –  Fats (particularly triacylglycerols)

•  Digestion reduces biomolecules to monomers –  Amino acids –  Nucleotides –  Monosaccharides –  Fatty acid


Starchy foods are hydrolyzed by amylases.

Bond broken

Amylases are found in the salivary glands


Proteins are hydrolyzed by proteases.

Proteases are secreted in the stomach and pancreas.


Fatty acids are hydrolyzed by lipases.

Remember: Fatty acids are technically not

polymers.

Lipases are made in the

pancreas and secreted in the

small intestines.


Monomers are stored as polymers.

Fatty acids are stored

in the form of triacylglycerols (large globules) in adipocytes.


Some tissues use monosaccharides to produce glycogen.

Glycogen Structure

Electron Micrograph of a Liver Cell

Glycogen Granules

(pink)

Fat Globule (yellow)

Mitochondria (green)


Glycogen breakdown occurs via phosphorolysis.


Some major metabolic pathways share a few common intermediates.


Some major metabolic pathways share a few common intermediates.

Glucose Catabolism


Many metabolic pathways include oxidation-reduction reactions.

•  Catabolism of amino acids, monosaccharides, and fatty acids involves oxidizing carbon.

•  Anabolism of amino acids, monosaccharides, and fatty acids involves reducing carbon.

Carbon in methane is most highly reduced.

Carbon in CO2 is most highly

oxidized.


Carbons in fatty acids and carbohydrates are oxidized to CO2.

Fatty acids have many methylene

carbons that undergo

oxidation.

Carbohydrates have (CH2O) carbons that

undergo oxidation.


Overview of Metabolism

•  Monomers are formed.

•  Intermediates with two or three carbons are formed.

•  Carbons are fully oxidized to CO2.

•  Electron carriers gain electrons.

•  Electron carriers are recycled via electron loss.

•  ATP and H2O are produced.


Humans do not synthesize vitamins.


ATP is often involved in coupled processes.

Cleavage of phosphoanhydride

bonds yields energy to drive

unfavorable reactions.


Consider the following reactions.

A highly favorable reaction

A highly unfavorable reaction © 2014 John Wiley & Sons, Inc. All rights reserved.

What’s so special about ATP?

•  ATP hydrolysis drives many unfavorable reactions to completion.

•  As a result, ATP acts as “energy currency”.


Glucose Metabolism

•  Glycogen breakdown

•  Glycolysis

•  Gluconeogenesis

•  Glycogen synthesis


Glycolysis Overview

•  Glycolysis occurs in 10 steps. – Steps 1-5 = energy investment – Steps 6-10 = energy payoff

•  Glucose (a six-carbon molecule) is broken

down into two 3-carbon molecules.

•  Electron carriers are reduced.


First 5 Steps of Glycolysis


Last 5 Steps of Glycolysis


What happens to pyruvate?


Pyruvate is a precursor of oxaloacetate.

•  Oxaloacetate is a metabolite used in: – The citric acid cycle – Gluconeogenesis

•  Oxaloacetate is also an intermediate in amino acid synthesis.


Overview of Gluconeogenesis •  Many glycolytic

enzymes are used.

•  Four new enzymes –  Pyruvate carboxylase

–  Phosphoenolpyruvate carboxykinase

–  Fructose bisphosphatase

–  Glucose-6-phosphatase


If glycolysis and gluconeogenesis occurred simultaneously, there

would be a net consumption of ATP!

•  Goal of producing ATP would be futile!

•  Instead, glycolysis and gluconeogenesis are regulated based on the cell’s needs.


Glycogen synthesis consumes the free

energy of UTP.

•  Hydrolysis of inorganic pyrophosphatase drives the reaction.

•  UDP-glucose is the major intermediate.


Glycogen synthase adds glucose to extend the glycogen polymer.


Glycogenolysis

•  Glycogen breakdown occurs via different reactions. –  Linear chains are broken down via phosphorolysis. –  Branched chains of glycogen are broken down via

hydrolysis.

•  Glucose-6-phosphate can enter glycolysis at Step 2. –  One less ATP is consumed compared to glucose from the

bloodstream. –  Net gain of ATP is higher!


Oxidative reactions of the pentose phosphate pathway produce NADPH.


Net Reaction for the Pentose Phosphate Pathway

•  Ribose derivative is produced.

•  2 NADPH molecules are formed.

•  Pathway is active in rapidly dividing cells.


Summary of Glucose

Metabolism


Overview of the Citric Acid Cycle


The citric acid cycle is an

energy-generating cycle.

•  1 NADH = 2.5 ATP •  1 QH2 = 1.5 ATP


Overview in Context


Recap on Oxidation-Reduction

•  One reactant is in its oxidized state while the other is in its reduced state.

•  Loss of electrons = oxidation •  Gain of electrons = reduction


Electron transport takes place in the mitochondrion.


Amino Acid Metabolism


Transamination moves amino groups between compounds.

•  Transaminase = aminotransferase •  A transaminase catalyzes the transfer of an amino group

to an α-keto acid. •  Transamination is reversible.


Nitrogen Metabolism in Context

•  Amino acids are synthesized from intermediates of glycolysis and the citric acid cycle.

•  Nonessential amino acids can be synthesized.

•  Essential amino acids must be obtained from food.



Amino acids can be classified in terms of their catabolism.

•  Glucogenic – giving rise to gluconeogenic precursors – Citric acid cycle intermediates, for example

•  Ketogenic – giving rise to acetyl-CoA – Used for ketogenesis or fatty acid synthesis – Not used for gluconeogenesis



Some amino acids are converted to gluconeogenic substrates via

transamination.


Some amino acids are converted to gluconeogenic substrates via

transamination.


Approximately 80% of excess nitrogen is excreted as urea.


Amino groups can be disposed of via two routes.


Lipid Metabolism In Context

•  Triacylglycerols contain fatty acids attached to a glycerol backbone.

•  Fatty acids are broken down

into 2C and 3C intermediates that feed into the citric acid cycle.


Triacylglycerols are the primary source of fatty acids.


Fatty acids are activated before they are degraded.

•  Activated fatty acids are acylated to CoA.

•  Reaction is

driven by ATP hydrolysis.


Each round of β oxidation has four reactions.

•  Acyl groups are transferred via carnitine.

•  Acyl-CoA is degraded into acetyl-CoA.


β Oxidation is a spiral process.

Let’s look at the reactions of β oxidation

more closely.


β Oxidation results in ATP production.


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Metabolism - StFX · Cells take up the products of digestion • Human diet consists of four types of biomolecules – Proteins – Nucleic acids – Polysaccharides