INTRODUCTION TO METABOLISM

Lourdes L. Balcueva,M.D.

General Objective:

To explain thoroughly how cells carry out and regulate complex reaction sequences.

SPECIFIC OBJECTIVES: 1. To be able to differentiate between anabolic and catabolic pathways. 2. To be able to explain briefly how carbohydrates, lipids and proteins are metabolized 3. To be able to correlate relationships between each pathways.

METABOLISM- entire network of chemical reactions carried out by living cells.

- living cells carry out thousands of reactions simultaneously;each reaction sequence is controlled so that unwanted accumulations or deficiencies of intermediate products do not occur

Metabolism includes:1. interconversion of chemical compounds in the body2. pathways taken by molecules3. interrelationships between the pathways4. regulating mechanisms

:

Metabolism can be divided into 2 categories:

.1.Catabolism- process related to

degradation of complex substances to

liberate smaller molecules and energy.

2. Anabolism- processes concerned

primarily with synthesis of complex

organic molecules needed for cell

maintenance, growth and reproduction.

3. Amphibolic- act as links between anabolism and catabolism; they are at the crossroad between the 2 pathways.

Intermediary Metabolism- applied to reactions involving the low molecular weight molecules that are metabolites in

of the degradation or biosynthesis of biopolymers.

Energy metabolism:

Part of intermediary metabolism consisting of pathways that store or generate metabolic energy.

Most organisms derive both the raw materials and the energy for biosynthesis from organic fuel molecules such as glucose.

Metabolic Pathways

Sequences of reactions that include the reactants, intermediates,products and the enzymes involved.

- 4 major groups of biomolecules whose metabolic pathways are considered separately:

1. carbohydrates 3. proteins

2. fats 4. nucleotides

Fed State- glucose is the major fuel; respiratory quotient- ratio of CO2 produced to oxygen consumed

insulin-controls uptake of glucose in muscle cell and adipose tissue

GLUT 4- glucose transporter in muscles and adipose tissues; responds to insulin secretion by migration to plasma membrane Liver and pancreas- independent of insulin

Glucokinase- liver enzyme W/ high Km but low affinity for glucoseGlucose 6-phosphatase- liver enzyme that hydrolyses G6PO4 release glucose into the blood

Erythrocytes- completely dependent on glucose for fuel (anaerobic glycolysis and pentose phosphate pathway Brain- uses mostly glucose for fuel; also some ketone bodies

Glucose + 6 O2

E

E

E

E

E

6 CO2 + 6 H2O

Reasons for multistep pathway:1. Limited reaction- specificity of enzymes; each active site catalyzes only a single step of the pathway2. To control energy input and output – energy flow is mediated by energy donors and acceptors

3. Catabolism of metabolic fuels yield 3 types of compounds that mediate the release of energy: 1) acetyl CoA 2) nucleoside triphosphate (ATP) 3) reduced coenzymes (NADH,FADH) 4. Some compounds can be substrates or products of more than 1 enzyme so they can have 2 or more metabolic functions.

5. To establish control points:

- balance of energy supply and

demand in living cells

- ability to respond to internal

signals or change in the

environment

Metabolic Regulation

Most pathways are irreversible under physiologic conditions

When a metabolite enters the pathway each step occurs in sequence w/out backing up or wasting cellular material or

energy

Reactions are regulated so as to proceed in only 1 direction

Patterns of Metabolic Regulation

1. Allosteric modification a.. Feedback inhibition-when the product

controls the rate of its own synthesis b.. Feedforward activation- when a metabolite produced early in the pathway activates an enzyme that catalyzes a reaction further down the pathway.

A B C D E P

2. covalent modification- alters catalytic rate by attachment to some grp. By a covalent bond (usually a phosphate group) phosphorylation: - activates enzymes regulating catabolic pathways - inhibits enzymes regulating anabolic pathways - catalyzed by protein kinases dephosphorylation: - inhibits enzymes regulating catabolic pathways - activates enzymes regulating anabolic pathways - catalyzed by protein phosphatases

3. Supply of substrate

ATP or ADP

4. Hormones

insulin

glucagon