Chapter 4 – Cellular Metabolism

Cellular metabolism enables the organism to grow.

You are responsible for the following figures and tables:

Fig. 4.14 - metabolic processes, anabolic and catabolic.Fig. 4.1, 4.2, 4.3 – Macromolecules.Fig. 4.4 - control of metabolism is achieved by enzymes.-see table summary in the attached lecture handout -Fig. 4.5 - metabolism occurs complex biochemical pathways.Fig. 4.15 - Metabolic reactions can be regulated by feedback mechanism.Read TB, p.108, on 'cellular respiration'. Fig. 4.6 - Cellular respiration consists of 3 biochemical pathways. -see table summaries in the attached lecture handout --see also Ch.9 regarding ‘oxygen debt’ resulting in the synthesis of lactate instead of pyruvate-Fig. 4.17, 4.18 - RNA and DNA. Fig. 4.24 – DNA. Fig. 4.22 - transcription – translationFig. 4.25 - Mutation Fig. 4.26 - Explain PKU.

Metabolic Processes

• Anabolism/synthesis is the process by which large molecules are built from smaller ones. Anabolism/synthesis often occurs through dehydration, that is, a water molecule is removed.

• Catabolism/degradation is the process by which large molecules are broken down/degraded into small ones. This often occurs through hydrolysis, that is, a water molecule is added.

Dehydration Synthesis

• Joins monosaccharides to form glycogen

• Joins glycerol and fatty acids to form fat molecules

• Joins amino acids by way of a peptide bond to form dipeptides, polypeptides, and proteins

Hydrolysis

• Breaks down carbohydrates into monosaccharides

• Breaks down fats into glycerol and fatty acids

• Breaks down proteins into amino acids

• Breaks down nucleic acids into nucleotides

Metabolic Pathways

• Regulatory enzymes can determine the rate of a metabolic pathway.

• Rate-limiting enzymes at the beginning of a pathway often become regulatory.

Metabolic Pathways

• Rate-limiting enzymes are the first enzyme in a series of enzymes that are all part of a metabolic pathway.

• Control of a rate-limiting enzyme prevents accumulation of intermediates.

• Products of metabolic reactions can inhibit the rate-limiting enzyme through negative feedback (Fig. 4.15).

Metabolism is made possible through the action of Enzymes

• Enzymes are globular proteins that promote chemical reactions by lowering the activation energy required to start the reaction and enhancing the reaction rate.

• They are catalysts that do not get chemically changed in the reaction themselves .

• Since they are not consumed by the reaction, they are needed only in very small quantities.

• Enzymes are specific and act only on particular substrates. There are enzymes that make bonds and synthesize molecules and there are those enzymes that break bonds and degrade molecules into smaller molecules.

Enzyme Catalyzing a Synthetic Reaction

• The active site of the enzyme combines with specific regions of the substrate, forming an enzyme-substrate complex.

E + S ES P

Fig. 4.4

Cofactors and Coenzymes

• Enzymes are often inactive until combining with cofactors or coenzymes.

• Cofactors are inorganic ions, such as zinc, copper, calcium, or iron.

• Coenzymes are small organic molecules that are often vitamins or derived from vitamins.

Denaturation

• Enzymes, like all proteins, can be denatured.

• A denatured protein has an altered structure and can inactivate a complete metabolic pathways (Fig. 4.5- envision inactivation of enzyme A).

• Proteins can be denatured by heat, radiation, certain chemicals, pH extremes.

Release / Storage of Chemical Energy: ATP

Metabolism depends on chemical energy.

• Initially, cellular respiration, a catabolic process in liver or muscles, releases energy from molecules.

• The prime molecule that is degraded is glucose which is taken up with the food.

• The processes occur in the cytosol and in the mitochondria that are located in the cytosol.

• This process is usually aerobic, in the presence of oxygen

Release of Chemical Energy During Cellular Respiration in a Muscle Cell

Fig. 4.6

Cellular respiration, a catabolic process, occurs inthree reactions:

glycolysis citric acid cycleelectron transport chain /oxidative phosphorylation.

• Glycolysis occurs in the cytosol of a liver or muscle cell. • Citric acid cycle (also called TCA cycle and Krebs cycle) and

the electron transport chain occur inside the mitochondrium.• In the process of the reactions, 34 to 38 ATP, are released.• AdenosineTriPhosphate or ATP is a molecule that stores high

energy in its covalent bonds (Figs. 4.7 and 4.8). Note: In the absence of oxygen or unaerobic respiration, pyruvate isconverted to lactate which correlates with muscle cramps.

Adenosine Triphosphate (ATP)

• The third phosphate is attached with a high energy bond.

• This chemical energy can be easily transferred to other molecules in metabolic processes. Figure 4.7

CELLULAR RESPIRATION = Need for O2 and Release of CO2 as waste from tissues

GLYCOLYSIS CONVERSIONSTEP

CITRIC ACID CYCLE

ETC

LOCATION cytoplasm mitochondria Mitochondrial matrix

mitochondrial inner membrane

O2 Required? NO yes yes yes

StartingProduct

glucose (6-C)

2 pyruvates (2 x 3C)

Acetyl CoA (2 x 2C)

10 NADH 2 FADH2

End-Products

2 pyruvates(2 x 3-C)2 -4 ATP2 NADH

2 Acetyl CoA2 NADH2 CO2

6 NADH2 FADH2

2-4 ATP4 CO2

30 ATP 2-4 ATP 2-4 ATP

TOTAL 34-38 ATP

Glycolysis

• It converts a 6-carbon glucose molecule into two 3-carbon pyruvic acid molecules.

• Glycolysis is anaerobic; it does not require oxygen to proceed.

• NADH is produced through the release of hydrogen atoms which are carried by NAD+ to the electron transport chain.

• ATP is synthesized.

Anaerobic Respiration

• Oxygen is the electron acceptor in the electron transport chain allowing NADH + H+ to deliver electrons and replenish NAD+..

• Without oxygen, NADH + H+ releases H+ ions and electrons to pyruvic acid, forming lactic acid.

• This is anaerobic metabolism.

* Lactic acid leads to muscle cramps.

Aerobic Respiration (Fig. 4.12)• When O2 is available, pyruvic acid moves from cytosol

into mitochondria.

Citric Acid Cycle Cycles Organic Acids

• The cycle occurs in the mitochondrial matrix.• 2-carbon acetyl CoA combines with 4-carbon

oxaloacetic acid to form 6-carbon citric acid. Coenzyme A is released.

• A series of reactions regenerate oxaloacetic acid and produce ATP, NADH + H+, FADH2, and three carbon dioxides (CO2).

• This cycle can be repeated as long as oxygen and pyruvic acid are available.

* CO2 will leave the body via the lungs when O2 is breathed in.

Electron Transport Chain

• Electrons are transferred through a series of enzyme complexes on the inner mitochondrial membrane.

• Ultimately, electron energy is transferred to ATP.

• O2 receives the H+ ions and electrons (e-) to form H2O.

Metabolic Pathways of Carbohydrates Excess glucose may enter anabolic carbohydrate

pathways leading to the synthesis of glycogen or fat.

Fig. 4.13

• Liver and muscle store glycogen.• Glucose can also be converted to fat molecules

and stored in adipose tissue.

• Carbohydrates can give their energy for growth processes:

DNA synthesis / replication transcription and translation

Metabolic Pathways of Carbohydrates

Genetic Information

• Genetic information is contained in the specific nucleotide sequence of DNA called a gene.

• The portion of the DNA molecule that contains genetic information for a particular protein is a gene.

• The DNA contained in each somatic or body cell constitutes the complete set of genes also called the genome.

DNA Structure (Figure 4.19)• A DNA molecule consists of a double helix of two

polynucleotide chains that are oriented antiparallel to each other

• The chains are held together by H-bonds between the bases of each nucleotide.

• Nucleotides consist of a sugar, a base, and a phosphate (Fig. 4.16).

• There are four bases in DNA: adenine (A), Thymine (T), Guanine (G), Cytosine (C).

• These bases exhibit complementary base pairing: A pairs with T G pairs with C.

DNA Replication• DNA replication

creates an exact copy of a DNA molecule.

• Replication occurs during interphase of the cell cycle.

• Following replication, mitosis can occur.

Figure 4.24

DNA Replication

• The enzyme DNA polymerase catalyzes the process of DNA duplication.

• Hydrogen bonds between paired bases break and new nucleotides that are brought in by DNA polymerase base pair with the original strand.

• The resulting double-stranded DNA molecules contain one strand from the original molecule and one new complementary strand.

Genetic Code• The genetic code is preserved in the

process of transcription followed by translation.

• Each of the twenty different amino acids is represented in the DNA molecule by a triplet of three nucleotides called a triplet code also known as the genetic code.

• For example CGT represents one amino acid while GCA represents another.

• Triplets of nucleotides also provide stop and start signals for protein synthesis.

Transcription (Figure 4.22)

Transcription (Figure 4.22)• The first step in delivery of genetic information is synthesis of messenger RNA (mRNA) in a process called transcription.

• mRNA is synthesized in the nucleus.

• Synthesis of messenger RNA (mRNA): The DNA double helix unwinds in one region, exposing the gene.

Transcription• The enzyme RNA polymerase binds to the DNA

and creates a mRNA copy by matching complementary base pairs A-U and G-C.

* mRNA has uracil (U) and no thymine (T).

• At a stop signal in the gene, the mRNA molecule is released into the nucleoplasm.

• The region on the gene which has been transcribed into a mRNA rewinds back into a double helix.

• mRNA is then transported to the cytoplasm for translation into a protein.

RNA Molecules• RNA

molecules are single strands containing the sugar ribose instead of deoxyribose.

Figure 4.20

Protein Synthesis (Translation)• Three mRNA

nucleotides code for one amino acid each and are called a codon.

• Transfer RNA (tRNA) for each amino acid align amino acids in the ribosome binding site.

• A protein is released. Figure 4.23

Mutations-Changes in Genetic Information

• Mutations occur when DNA is damaged or replication mistakes occur.

• Mutations occur when a base is paired incorrectly or a base is inserted or deleted.

• In all cases DNA information is altered.• Repair enzymes generally correct mutations. But

sometimes they fail to do so.• Mutagens are chemicals that cause mutation.

Mutations lead to altered phenotype or cancer.