HB09 / NHB1206

Metabolism

Introduction to metabolism

Dr R Sanjeev,
Department of Human Biology
 ILO
• Describe the significance of metabolism in medicine.

• Explain the various types of coenzymes and cofactors

involved in metabolism
 Digestion, Absorption and
Metabolism

• Digestion enables nutrients to be

absorbed.

• Absorption into the blood

enables them to be utilized

• Metabolism refers to all the

chemical changes which take
place in the body.
Overview of Digestion Absorption & Metabolism
Glucose transport- Home work

RECALL :
Glucose transport
mechanisms
1) Na+ & ATP independent
transport system(14 glucose
transporters)
2) Na+ & ATP dependent
cotransport system
Digestion of Proteins
Absorption of Proteins - Refer
Digestion & Absorption of Lipids
• Average daily intake of lipids 35 g in Sri
Lankan adults
• In that > 90% is TAG (3FA + Glycerol)
• Reminder ; cholesterol, cholesterol esters,
phospholipids & FFA
• Digestion begins in stomach & ends in SI.
OVERVIEW OF LIPID DIGESTION
Digestion of Lipids
FOOD--- METABOLISM---- ATP
Metabolism
 Metabolism

Is the sum total of all chemical reactions involved in maintaining

the living state of the cells, and thus the organism.

• The three main purposes of metabolism are:

1) The conversion of food to energy to run cellular processes
2) The conversion of food/fuel to building blocks for proteins, lipids, nucleic
acids, and some carbohydrates
3) The elimination of metabolic wastes
 Metabolism

Divided into two categories;

1. Catabolism – break down of molecules

to obtain energy

2. Anabolism- the synthesis of all

molecules needed by cells
e.g. DNA, protein etc.
Catabolism Vs Anabolism
 Anabolism Catabolism

large complex organic Decomposition of large complex

molecules are constructed molecules into small molecules
from small molecules

Biosynthetic Degradative

Reductive Oxidative

Energy Required Energy Liberated

Divergent process Convergent process
(Few precursors-- wide (wide variety of complex products
variety of complex products) precursors-- Few common products)
Catabolism and anabolism are always related
Nutrients Macromolecules
Carbohydrates Proteins
Fats Polysaccharides
Proteins Lipids
Nucleic acids

GTP
ATP
NADPH
Catabolism NADPH Anabolism
Chemical
(oxidative, (reductive,
energy
exergonic) NADPH NADH endergonic)
ATP
ATP
Precursor Molecules
End products Amino acids
Sugars
H2O, CO2, NH3 Fatty acids
Nitrogenous bases
 Stages of catabolism
1. Hydrolysis of complex molecules
Eg: Protein  amino acids
Polysaccharidesmonosaccharides
Fat (TAG)  Free FA + Glycerol
2. Conversion of building blocks to simple
intermediates
- these building blocks are further degraded to
acetyl CoA & simple
molecules
- little energy produced during this stage
3. Oxidation of acetyl CoA
- TCA cycle is the final common pathway
- oxidation of acetyl CoA generates large
amount of ATP
ATP Powers Cellular Work
Unstable
Bonds—can release
energy when
broken

Energy transferred to
another molecule (phos-
phorylated intermediate)
with the phosphate

Less stable More stable

What carries energy???? ATP

• The energy currency or coin

of the cell
• Energy rich molecule
• Triphosphate contains 2
phosphoanhydride bonds

the energy is stored in ATP

• 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 ~ 40kg of ATP/ 24 hr.

Motion, Active transport,

ATP
Biosynthesis, Signal amplification
ADP
Photosynthesis or oxidation of fuel
molecules

Basic model of energy exchange in biological systems

 Pi
P

Motor protein Protein moved

Mechanical work: ATP phosphorylates motor proteins

Membrane
protein ADP
+
ATP Pi

P Pi

Solute Solute transported

Transport work: ATP phosphorylates transport proteins

P
NH2
+ NH3 + Pi
Glu
Glu

Reactants: Glutamic acid Product (glutamine)

and ammonia made
Chemical work: ATP phosphorylates key reactants
 How do cells make ATP?
• By PHOSPHORYLATION... adding a phosphate to ADP
ADP + P ------> ATP

3 mechanisms of phosphorylation:

1. substrate level phosphorylation- where a

substrate molecule ( X-p ) donates its high
energy P to ADP making ATP

2. Oxidative phosphorylation
e- transferred from organic molecules and
passed through a series of acceptors to O2

3. 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
How does the e- get to oxygen???????
e- O2
• ANS: Electron carriers

NAD+ (nicotinamide adenine dinucleotide) and

FAD (flavin adenine dinucleotide)
• Reduced form (with electrons bound) are NADH and FADH2

- NADH and FADH2 transfer e- to O2 in the mitochondria by means of ETC >

ATP generated in this process
Cofactor Vs Coenzyme
 Metabolic Pathways

Sequential steps catalyzed by enzymes

intermediates

A B C D

 A is a precursor for B, C and D metabolites of A

 B is a precursor for C and D
 C is a precursor for D
 Characteristics of Metabolic Pathways

 Metabolic pathways have reversible & irreversible reactions

GLYCOLYTIC PATHWAY
 Metabolic pathways have committed step
 Early step unique to a pathway
 Irreversible step
 Requires energy
 Often results in a phosphorylated compound

 Metabolic pathways are regulated

 Metabolic pathways are compartmentalized.

1) Rate-determining step / Rate-limiting step.

• In chemical kinetics, the overall rate of a reaction is often

approximately determined by the slowest step, known as the rate-
determining step (RDS) or rate-limiting step.

2) Committed step
• In enzymology, the committed step is an
effectively irreversible enzymatic reaction that occurs at a branch
point during the biosynthesis of some molecules.
• The committed step is the one after which the substrate has only one
way to go.
 Cellular level Compartmentation

Mitochondria (TCA cycle, fatty acid oxidation,

amino acid breakdown)

Cytosol (glycolysis, fatty acid biosynthesis,

pentose phosphate pathway)
 Regulation of Metabolism
• How does the body know when to increase metabolism? Slow
metabolism?
Requires communication

• What might be some indicators of energy status within the cell?

Works through allosteric regulation of enzyme activity

 Recall HB03
Mechanisms of Cellular Communication
 Recall HB03

Eg: acetylcholine, the catecholamines, serotonin, glutamate, GABA,

glycine, and a wide variety of neuropeptides
 Recall HB03

Eg: oxytocin and the antidiuretic hormone

 Recall HB03

Figure 6-2a
 What Hormones Regulate Metabolism?
• Insulin
• Glucagon
• Thyroid hormone
• Cortisol
• Epinephrine

Most regulation occurs in order to maintain stable

blood glucose concentrations for supplying fuel to
the brain!
 Recall HB03

Protein or peptide hormone

Almost always proteins called kinases

Activation/inactivation of an enzyme; opening/closing a

membrane channel; activating a transcription factor
 Recall HB03
Steroid Hormones
(examples: cortisol, testosterone, estrogen

Figure 6-4 (2 of 3)
Protein/peptide hormones Recall HB03

(examples: epinephrine, insulin, glucagon, oxytocin)

Recall HB03
 Recall HB01
Control of metabolic pathways
Molecular level:
Control of enzyme levels
gene expression (slow).
Control of enzyme activity (fast)
- allosteric control (binding of an effector at one site affects
enzyme activity at another site).
- covalent control (phosphorylation, adenylylation, etc).
Recall HB01
Recall HB01
Putting It All Together
• The digestive process
Absorb
into
Eat food circulation

Digest to food to Deliver

nutrients in the GI nutrients
tract to the cells