Essential Biochemistry · 2016-03-17 · Glycogenolysis • Glycogen breakdown occurs via different...

Post on 20-May-2020

8 views 0 download

Transcript of Essential Biochemistry · 2016-03-17 · Glycogenolysis • Glycogen breakdown occurs via different...

Lecture Notes for

Chapter 12/13/14/15 Metabolism I

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

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

Starchy foods are hydrolyzed by amylases.

Bond broken

Amylases are found in the salivary glands

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

Proteins are hydrolyzed by proteases.

Proteases are secreted in the stomach and pancreas.

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

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.

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

Monomers are stored as polymers.

Fatty acids are stored

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

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

Some tissues use monosaccharides to produce glycogen.

Glycogen Structure

Electron Micrograph of a Liver Cell

Glycogen Granules

(pink)

Fat Globule (yellow)

Mitochondria (green)

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

Glycogen breakdown occurs via phosphorolysis.

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

Some major metabolic pathways share a few common intermediates.

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

Some major metabolic pathways share a few common intermediates.

Glucose Catabolism

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

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.

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

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.

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

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.

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

Humans do not synthesize vitamins.

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

ATP is often involved in coupled processes.

Cleavage of phosphoanhydride

bonds yields energy to drive

unfavorable reactions.

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

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”.

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

Glucose Metabolism

•  Glycogen breakdown

•  Glycolysis

•  Gluconeogenesis

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

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.

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

First 5 Steps of Glycolysis

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

Last 5 Steps of Glycolysis

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

What happens to pyruvate?

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

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.

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

Overview of Gluconeogenesis •  Many glycolytic

enzymes are used.

•  Four new enzymes –  Pyruvate carboxylase

–  Phosphoenolpyruvate carboxykinase

–  Fructose bisphosphatase

–  Glucose-6-phosphatase

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

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.

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

Glycogen synthesis consumes the free

energy of UTP.

•  Hydrolysis of inorganic pyrophosphatase drives the reaction.

•  UDP-glucose is the major intermediate.

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

Glycogen synthase adds glucose to extend the glycogen polymer.

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

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!

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

Oxidative reactions of the pentose phosphate pathway produce NADPH.

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

Net Reaction for the Pentose Phosphate Pathway

•  Ribose derivative is produced.

•  2 NADPH molecules are formed.

•  Pathway is active in rapidly dividing cells.

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

Summary of Glucose

Metabolism

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

Overview of the Citric Acid Cycle

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

The citric acid cycle is an

energy-generating cycle.

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

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

Overview in Context

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

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

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

Electron transport takes place in the mitochondrion.

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