MCB 32 Introductory Human Physiology

Kelly Kruger

Notes for Thursday August 31

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OUTLINE FOR LECTURE 2

Reference for Lecture 2

Biology by Neil Campbell et al., 5th Edition, pps.147-165

On two hour reserve at Biological Sciences library

l. Enzymes

Enzymes are biological catalysts

catalysts speed up the rate of chemical reactions, without themselves being changed

enzymes accomplish this by lowering the activation energy of a biochemical reaction

many enzymes require cofactors

cofactors include inorganic ions or organic (non-protein molecules) required for activity

many cofactors have vitamins as their precursors

organic factors are called coenzymes

Types of enzymatic reactions

1) oxidation-reduction (redox reactions) - transfer electrons or protons (H⁺) between

atoms, ions or molecules

2) hydrolysis - dehydration

hydrolysis - the breakdown of a molecule by the addition of water (H₂0)

dehydration - the synthesis of a molecule from two others that results in the production of a water molecule

3) transfer reactions

addition-subtraction- exchange reactions

addition reaction - adds a functional group to one or more of the reactants e.g., add phosphate (phosphorylase)

subtraction reaction - removes a funtional group from one or more reactants e.g. subtract a phosphate (phosphatase)

exchange reaction - functional groups are exchange between or among reactants, e.g. the exchange of a phosphate group (kinase)

ll Cellular Metabolism

Organic compounds store energy in their arrangement of atoms.

With the help of enzymes, a cell systematically degrades complex organic molecules (the food we eat) that are rich in potential energy to simpler waste products that have less energy.

The energy released during this process can be used to do work; the rest is dissipated as heat.

Metabolic pathways that release stored energy by breaking down complex molecules are called catabolic pathways.

Catabolism is linked to work in biological systems by the high energy storage molecule, ATP (adenosine triphosphate).

The price of most cellular work is the conversion of ATP to ADP and inorganic phosphate P_i products that store less energy than ATP.

To keep working the cell must regenerate its supply of ATP from ATP and inorganic phosphate.

A working muscle recycles its ATP at a rate of about 10 million molecules per second!!

To understand how the cell regenerates ATP, we must examine the fundemental chemical processes of oxidation and reduction.

In many chemical reactions there is a transfer of one or more electrons (e^-) from one reactant to another.

These electron transfers are called oxidation-reduction reactions or redox reactions.

redox reactions

oxidation is the loss of electrons from one substance

reduction is the addition of electrons to another substance

In cellular respiration glucose is oxidized and oxygen is reduced, and electrons lose potential energy along the way.

Electrons removed from glucose are shuttled to the top of the electron transport chain. At the bottom of the chain oxygen captures these electrons along with hydrogen nuclei ( H⁺) forming water.

Summary of cellular respiration

C₆H₁₂0₆ + 6O₂-----> 6CO₂ + 6H₂O + energy

For each molecule of glucose degraded to carbon dioxide and water by respiration, the cell makes up to 38 molecules of ATP.

Respiration is the cumulative function of three metabolic stages:

1) glycolysis

2) the Krebs cycle

3) the electron transport chain and oxidative phosphorlyation

The first two stages, glycolysis and the Krebs cycle are the catabolic pathways that decompose glucose and other organic fuels.

Glycolysis

takes place in the cytosol

occurs in the presence or absence of oxygen

a molecule of glucose is broken down into two three-carbon sugar molecules, ultimately producing two molecules of pyruvate

Glycolysis can be broken down into two phases:

an energy investment phase (the first five steps) and

an energy producing phase(the next five steps) when ATP produced

the net energy yeild of glycolysis is two molecules of ATP and NAD⁺ is reduced to NADH

if molecular oxygen (O₂) is present , NADH can be converted to ATP by the electron transport chain

glycolysis releases less than a quarter of the chemical energy stored in glucose

in the absence of oxygen, NAD⁺ is regenerated by the transfer of its electrons from NADH to pyruvate generating lactic acid

Krebs cycle

if molecular oxygen is present, pyruvate enters the mitochondrion where the enzymes of the Krebs cycle complete the oxidation of organic molecules

pyruvate is converted to acteyl CoA, which enter the Krebs cycle

each step in the Krebs cycle is catalyzed by a specific enzyme in the mitochondrial matrix

for each turn of the Krebs cycle two carbons enter in a fairly reduced form of acetate and two different carbons exit in a completely oxidized form, CO₂

most the energy generated by the oxidative steps of the cycle is conserved in NADH, by redox reactions that transfer of electrons from substrates to NAD⁺

for each acetate molecule that enters the cycle three molecules of NAD+ are reduced to NADH; in one step electrons are transferred to a different electron acceptor FAD generating FADH₂

there is also a step in the Krebs cycle where an ATP is generated by substrate level phosphorylation

glycolysis and the Krebs cycle produce a total of 4 molecules of ATP per glucose molecule by substrate level phosphorylation, two ATPs from glycolysis and two from the Krebs cycle

the molecules of NADH and FADH₂ account for most of the energy extracted from food

NADH and FADH₂ link glycolysis and the Krebs cycle to the machinery for oxidative phosphorylation, which uses energy released by the electron transport chain to power ATP synthesis

The electron transport chain

a collection of molecules embedded in the inner membrane of the mitochondrion

most components of the chain are proteins; tightly bound to these proteins are prosthetic groups, non-protein groups essential for the catalytic functions of of certain enzymes

during electron transfer along the chain, these prosthetic groups alternate between reduced and oxidized states as they accept and donate electrons

the electron transport chain accepts electrons from the first two stages of glycolysis, usually via NADH and passes these electrons from one molecule to another along the chain

at the end of the chain, the electrons are combined with hydrogen ions and molecular oxygen to form water

energy released at steps in the electron chain is stored in a form the mitochondrion can use to make ATP

this mode of ATP synthesis is called oxidative phosphorylation because it is powered by redox reactions

oxidative phosphorylation accounts for 90% of the ATP generated by respiration

the energy released by electron tranfer down the electron transport chain is used to pump protons (H⁺) from the mitochodrial matrix across the inner mitochrondrial membrane

pumping the charged protons across the membrane establishes an electrochemical gradient of protons

the protons flow down their electrochemical gradient through the protein enzyme ATP synthetase, driving the generation of ATP molecules

Lactic acid metabolism

Skeletal muscle during strenous exercise consumes ATP more quickly then can be be provided by oxygen

the muscle generates pyruvate and ATP anaerobically by glycolysis; pyruvate is converted to lactate, which builds up (cramps)

high concentrations of lactic acid are toxic to cells, so most cells can rely on glycolysis only for short periods

The Versatility of Catabolism

Free glucose molecules are not common in our diet.

We obtain most of our calories in the form of fats, proteins, proteins, sucrose and other disaccharides and starch, a polysaccharides

All these food molecules can be used by cellular respiration to generate ATP

Glycolysis can accept wide range of carbohydrates for cellular metabolism. Starch can be hydrolyzed to glucose. Glycogen, the polysaccharide that humans store in their liver and muscle can be hydrolyzed to glucose.

Excess amino acids can be converted to intermediates of glycolysis and the Krebs cycle, following removal of their amino groups by a process called deamination.

After fats are digested, the glycerol can be converted to glyceraldehyd-3-phosphate; an intermediate in glycolysis.

Most of the energy of fat is stored in fatty acids. A metabolic sequence called beta- oxidation breaks fatty acids down to 2-carbon fragments, which enter the Krebs cycle as acetyl CoA.

Fats make excellent fuel. A gram of fat oxidized by respiration produces more than twice as much ATP as a gram of carbohydrate.

Biosynthesis (Anabolic Pathways)

Often our body needs specific molecules provided that are not present in our food.

Compounds formed as intermediates in glycolysis and the Krebs cycle can be diverted into anabolic pathways as precursors from which the cell can synthesize the molecules it needs.

For example, humans can make half of the twenty amino acids in proteins by modifying compounds from the Krebs cycle