Course Requirements

• Required Texts:– Biochemistry, Campbell and Farrell, 6th edition.

Publisher 2008– Lippincott’s Illustrated Reviews Biochemistry, 4th

edition. Publisher 2008

The study of carbohydrates and lipids metabolism

• I-Introduction:– Definition

• metabolism of carbohydrates – Digestion of carbohydrates– Glycolysis– Tricarboxylic acid cycle– Glycogen metabolism – Gluconeogensis – Pentose phosphate pathway and NADPH – Metabolism of monosaccharides and disaccharides

Lipids metabolism

– Digestion of dietary lipids • How fats are digested in animals• How fats are mobilized and transported in tissues• How fats are oxidized• How “ketone bodies” are produced

– Fatty acid and triacylglycerol metabolism – Biosynthesis of Complex lipid metabolism – Biosynthesis Cholesterol and steroidhormones

General metabolismBioc 211

http://www.runningforfitness.org/book/chapter-7-eating-drinking-and-running/energy-while-running

How the body converts food to energy?

• We are going to look at two major questions in biochemistry– How do cells extract energy from their

environment?– How do cells synthesis the building blocks of

their macromolecules?• This leads to the study of ..........

Campbell’ Chapter 15, P417Introduction to Metabolism

The nature of Metabolism• Metabolism: the chemical reactions of biomolecules, the sum

total of all biochemical reactions that take place in an organism . It is the biochemical basis of life processes

• Characters– Catalyzed by a specific enzyme

• Each reaction require a specific enzyme– Typically occur in pathways ( in a sequence)

• Several reactions in a row– Two major groups

• Catabolism: the breakdown of complex substances Usually energy-yielding!.

• Anabolism: the synthesis of complex substances needed by cells from simpler ones such as DNA Usually energy-requiring!.

Major purpose

• living things require energy for:

1- Mechanical work in muscle contraction and other cellular movement

3- Active transport of molecules and ions

2- Synthesis of biomolecules and simple precursors

What carries this energy??????

• The energy currency or coin of the cell is

• Energy rich molecules triphosphate contains 2 phosphoanhydride bonds

The 2 phosphate bonds (phosphoanhydride bond) is here the energy is stored in ATP

The energy• A large amount of energy

is liberated when – ATP → ADP + Pi

(orthophosphate)– ATP → AMP + PPi

(pyrophosphate)• The free energy liberated

with the hydrolysis of ATP is used to drive reactions that require input of free energy

The energy

• ATP is continuously formed and consumed• It’s the principal immediate donor and not

long term storage of energy• Rate of turnover of ATP is high. A molecule of

ATP is consumed within a minute it is formed• Resting person consumes 40 kg of ATP / 24hr

How do cells make ATP?

• By phosphorylation... adding a phosphate to ADP ADP + P - - - - - -> ATP

• 3 mechanisms of phosphorylation:– Substrate level phosphorylation ( where a substrate

molecule (X-P) donates its high energy P to ADP making ATP)– Oxidative phosphorylation (e- transferred from organic

molecules and passed through a series of acceptors to O2)– Photophosphorylation ( occurs during photosynthesis-

light energy used to make ATP)

Electron carriers• When food molecule oxidized – electrons are

removes• These electrons are carried to oxygen

• NAD+/ FAD• Reduced form with electrons bound is NADH/ FADH2

• NADH/ FADH2 transfer e- to O2 in the mitochondria by means of ETC ( ATP generated in this process)

How does the e- get to oxygen??????

Answers: electron carriers

O2e-

The nature of Metabolism

• Complex substances are broken down for energy, required metabolites, structural components, etc.

• Cells must synthesize new complex substances.

• Thousands of such reactions are occurring simultaneously in a single cell.

The nature of Metabolism (cont’d)

• These rxns occur with a minimum of side products, energy loss or undesired interferences and at reasonable temperatures, pH and pressure.

• All of these rxns must be controlled or regulated for optimum efficiency.

Free Energy Changes in Metabolism

• Overall G is negative (-) for catabolic processes

• For an anabolic process, the G ought to be positive (+)

• So generally catabolic processes generate energy for anabolic processes

General Principles:

• Metabolic pathways are irreversible (because they must be regulated)

• Metabolic pathways have (first) committed step

• Metabolic pathways are regulated • Metabolic pathways are compartmentalized

Principles (cont’d):• Metabolic reactions are often reversible• Processes of metabolism are highly

controlled:– Anabolism and catabolism are not usually

balanced - one or the other may predominate in certain cells or at different times depending on cell needs

– The pathway to synthesize a complex substance is not simply the reverse of the degradative pathway.

Principles (cont’d): • Metabolic pathways are compartmentalized• Cytosol (glycolysis, fatty acid biosynthesis,

pentose phosphate cycle)• Mitochondria (TCA cycle, OxPhos, fatty acid

oxidation, amino acid breakdown)• Nucleus (DNA replication, transcription, RNA

processing)• ER

– Rough ER: synthesis of membrane and secretory proteins– smooth ER: lipid and steroid biosynthesis

• Golgi (posttranslational processing of proteins)

Catabolism• catabolism: the breakdown of larger molecules into

smaller ones; an oxidative process that releases energy– Breakdown of monomers to common intermediates,

and thus to CO2 and electrons is accomplished through a central oxidative pathway:

• The Citric Acid Cycle or TCA or the Krebs Cycle. • This cycle leads to the production of ATP by

processes called electron transport and oxidative phosphorylation.

Glucose/other sugars Glycerol/fatty

acids

Pyruvate

Acetyl CoA

Citric acid cycle →ETS/OxPhos →ATP

NH4+

Amino acids

Oxidative processes produce ATP & NADH for energy

Co2

CatabolismpolysaccharidesProteins lipids

Anabolism

• Anabolism: the synthesis of larger molecules from smaller ones; a reductive process that requires energy– utilization of critical Common intermediates

including components of TCA cycle to make building blocks

• Making building block requires energy = ATP• Synthesis of macromolecules requires energy =

ATP • note CO2 not generally reused

Intermediates

Glucose/other sugars

Glycerol/fatty acids

Pyruvate

Acetyl CoA

Citric acid cycle

NH4+

Amino acids

Anabolism

ProteinsPolysaccharides

Lipids

Co2

Summary

• In catabolism, large molecules are broken down to smaller products, releasing energy and transferring electrons to acceptor molecules of various sorts. The overall process is one of oxidation.

• In anabolism, small molecules react to give rise to larger ones; this process requires energy and involves acceptance of electrons from a variety of donors. The overall process is one of reduction

A Comparison of Catabolism and Anabolism

• Metabolism is the sum total of the chemical reactions of biomolecules in an organism

AnabolismSynthesis reactions

CatabolismDegradation reactions

General description Building of a large molecule(polymer) from smaller building blocks (monomer):A + B → A--B

Breakdown of polymer intoindividual monomers:C—D → C + D

Descriptive terms Building, constructive, anabolic

Breakdown, digestive,decomposition, catabolic

Bond formed brokenEnergy Energy is required (=

Endergonic)Energy is released (= Exergonic)

Water Water is released (= Dehydration)

Water is required (= Hydrolysis)

Example Building a protein from individual amino acids;Building a triglyceride fromglycerol and 3 fatty acids, etc

Breaking a protein into individual amino acids;Breaking starch down intomonosaccharides, etc.

Anabolic vs catabolic reactions

General Pathways of Metabolism

Building blocks of the cellLarge units of the cell

Glucose, other sugars

Fatty Acids/ Glycerol

Amino Acids

Nucleotides

polysaccharides

Lipid membranes

proteins

Nucleic acids

Breakdown of macromolecules to building blocks generally hydrolytic

MetabolismII

Metabolism I

MetabolismEnergy-containing nutrients are processed in three major stages: 1. Digestion – breakdown of food; nutrients are transported to tissues 2. Anabolism and formation of catabolic intermediates where nutrients are:

- Built into lipids, proteins, and glycogen or- Broken down by catabolic pathways to pyruvic acid and acetyl CoA.

3. Oxidative breakdown – nutrients are catabolized to carbon dioxide, water, and ATP

Summarize

• Define metabolism• Distinguish between anabolism and

catabolism

Digestion of carbohydratesLippincott’s chapter 7, P86

The digestive systemPrepares food for use by all body cells

The digestive process involves a series of physical and chemical actions that break down the components of food into nutrient particles small enough for absorption

Digestion of Carbohydrates

• The principle site of carbohydrates digestion are the mouth and small intestine

• The dietary carbohydrate consist of:– Polysaccharides: starch glycogen and cellulose– Disaccharides: maltose, sucrose and lactose– Monosaccharides: mainly glucose and fructose

• No need for monosaccharides digestion prior to absorption, whereas di/polysaccharides must be hydrolysed to simple sugars before their absorption

Digestion of Carbohydrates• In the mouth - Chewing

increases surface area of food allowing salivary α-amylase to begin digestion of starch:

• Some of the free glucose in food can be absorbed through lining of the mouth

Digestion of Carbohydrates

• In the stomach – – Carbohydrates digestion

halts temporarily in the stomach

– Salivary amylase is inactivated by stomach high acidity.

Digestion of Carbohydrates• In the small intestine - the stomach

contents are neutralised by pancreatic juice.– Pancreatic amylase continues

digestion of starch to oligosaccharides and maltose.

– Intestinal brush border membrane enzymes

• Maltase hydrolyses maltose to glucose. • Sucrase hydrolyses sucrose to glucose +

fructose • Lactase hydrolyses lactose to glucose +

galactose – The end product of carbohydrates

digestion are glucose which are readily absorbed through the intestinal mucosal cells into the blood stream

Digestion of Carbohydrates• In the Large intestine

– Humans do not produce and secrete β-(1-4) endoglucosidase in digestive juice

• Humans unable to digest cellulose

• undigested fibre is attacked by bacteria (generates bowel gas).

• Fibre aids intestinal motility and acts as a softer

• Fibre is eventually excreted

Absorption of monosaccharides by intestinal mucosal cells• Different sugars have different mechanisms of

absorption:– Glucose & galactose actively taken up by mucosal cells

energy dependent secondary active transport (by Na+ pump).– Fructose is taken up by facilitative transport down

concentration gradient via passive carrier mediated transport.• Adsorbed sugars diffuse from intestinal mucosal cell

into portal circulation and are transported to the liver.

Absorption of monosaccharides by intestinal mucosal cells

Abnormal degradation of disaccharides• Hereditary deficiency• Mal nutrition• Drug injure the mucosa of the small

intestine• Lactose Intolerance - reduction in

amount of lactase produced (common in Asians & Africans). Lactose is not hydrolysed but enters the large intestine and draws water in by osmosis which causes diarrhoea. Lactose is metabolised by bacteria generating CO2 and H2. Milk products need to be avoided.

• Sucrose Intolerance - reduction in amount of sucrase produced. Symptoms similar to lactose intolerance (found in 10% of Greenland Eskimos).

Metabolic fate of carbohydrates• After being absorbed from the intestinal

tract the monosaccharides are carried by the portal circulation to the liver – In the liver D-glucose phosphorylated to

G-6-P– D-fructose and D-galactose are

phosphorylated to and convert to glucose in the liver

– G-6-P is an intermediate in several metabolic pathway that use glucose in the liver

– Depending on the supply and demand includes

• Glycolysis• Glycogenesis• Glycogenlysis • Gluconeogenesis• Pentose phosphate pathway

EtOH

Glucoseother sugars

Pyruvate

Acetyl CoA

Citric acid cycle→ATP

Pentose

GlycogenCarbohydrate Metabolism

Overview

Lactate

Metabolic fate of carbohydrates

Glycolysis

GlycogenlysisGlycogenesis

PPP

Gluconeogenesis

Summary• Salivary α-amylase acts on dietary polysaccharides (glycogen, amylose, amylopectin),

producing oligosaccharides. • Pancreatic α-amylase continues the process of polysaccharide digestion. • The final digestive processes occur at the mucosal lining of the small intestine. • Several disaccharidases [for example, lactase (β-galactosidase), sucrase, maltase, and

isomaltase] produce monosaccharides (glucose, galactose, and fructose). These enzymes are secreted by and remain associated with the luminal side of the brush border membranes of intestinal mucosal cells.

• Absorption of the monosaccharides requires specific transporters. • If carbohydrate degradation is deficient (as a result of heredity, intestinal disease,

malnutrition, or drugs that injure the mucosa of the small intestine), undigested carbohydrate will pass into the large intestine, where it can cause osmotic diarrhea.

• Bacterial fermentation of the compounds produces large volumes of CO2 and H2 gas, causing abdominal cramps, diarrhea, and flatulence.

• Lactose intolerance, caused by a lack of lactase, is by far the most common of these deficiencies.

Summarize

• The enzyme α–amylase:1. Hydrolyses glycogen to give glucose and maltose2. Is present in saliva3. Is activated by trypsin in the small intestine4. Hydrolyses cellulose to glucose and maltose5. If absent from pancreatic secretion, results in

incomplete digestion of starch, a large bacterial population in the faeces and diarrhoea

Q 1T/F

• The enzyme α–amylase:1. Hydrolyses glycogen to give glucose and maltose

(T)2. Is present in saliva (T)3. Is activated by trypsin in the small intestine (F)4. Hydrolyses cellulose to glucose and maltose (F)5. If ibsent from pancreatic secretion, results in

incomplete digestion of starch, a large bacterial population in the faeces and diarrhoea (T)

A 1 T/F

• The absorption of glucose in the digestive tract:1. Occurs in the small intestine 2. Is an energy-requiring process 3. Is stimulated by the hormone glucagon 4. Occurs more rapidly than the absorbtion of any

other sugar 5. Is impaired in cases of diabetes mellitus

Q2 T/F

• The absorption of glucose in the digestive tract:1. Occurs in the small intestine (T)2. Is an energy-requiring process (T)3. Is stimulated by the hormone glucagon (F)4. Occurs more rapidly than the absorbtion of any

other sugar (F)5. Is impaired in cases of diabetes mellitus (F)

A 2 T/F

• Diasaccharides in the diet, or those formed from polysaccharide digestion:1. Are absorbed as such by the small intestine 2. Are hydrolysed to constituent monosaccharides by

enzymes present in pancreatic juice 3. Are hydrolysed by specific enzymes of the small

intestine 4. Are quantitatively unimportant since there are no

enzyme deficiency diseases associated with their metabolism

Q 3 T/F

• Diasaccharides in the diet, or those formed from polysaccharide digestion:1. Are absorbed as such by the small intestine (F)2. Are hydrolysed to constituent monosaccharides by

enzymes present in pancreatic juice (F)3. Are hydrolysed by specific enzymes of the small

intestine (T)4. Are quantitatively unimportant since there are no

enzyme deficiency diseases associated with their metabolism (F)

A 3 T/F