Metabolism

• Metabolism – all chemical reactions necessary to maintain life.– Anabolic reactions – synthesis of larger molecules

from smaller ones. (dehydration synthesis)– Catabolic reactions –(hydrolysis) of complex

structures into simpler ones.

• Cellular respiration – food is broken down within cells to their basic organic building blocks. – The energy captured from the food is used to

produce ATP

Cellular Energy

• All cells require a constant supply of ATP. It is essentially the currency that all cells use for energy. Without a constant supply the cell will die.

• Specific proteins in the cell are capable of hydrolyzing ATP ATP ADP + P (energy released for reactions)

ATPase

ADP(adenosine diphosphate) and a phosphate group synthesize ATP by creating high energy bond between the 2nd and 3rd phosphate group

ADP + P ATP ( energy storing)

The energy from eating organic compounds provide the energy to create ATP

Cellular Energy

• The energy stored in the phosphate bonds of ATP originally comes from the plants ability to capture radiant energy from the sun. This allows the plants to convert inorganic molecules into organic molecules. This process called photosynthesis.

Radiant energy

• 6H2O + 6CO2 + 36 ATP C6H12O6 + 6O2 + 36 ADP +36 P

The energy is stored within the H’s of organic molecules (monosaccharides, fatty acids and amino acids).

• We eat the plants and animals that eat the plants. Our cells can extract the energy stored within the H’s and produce ATP

• The more H’s food has the more energy it contains.

Energy Metabolism

• During cellular respiration the energy stored in a glucose’s H are removed and taking to a specific part to the cell to harness the energy and make ATP. Several B vitamins are required for this process.

• 2 B-vitamin derivatives coenzymes NAD (niacin) and FAD (Riboflavin) are required for oxidation-reduction reactions to remove the hydrogen.

• These enzymes oxidizes sugar intermediates (loss of an electron/hydrogen atom)

NAD NADH reduced(gain of an electron/hydrogen atom)FAD FADH2 reduced• the reduced coenzymes are taken to the cristea of

mitochondria where 32 of the 36 ATP’s are formed.

Cellular Respiration

Cellular Respiration• Since all carbohydrates are transformed into

glucose, it is essentially glucose metabolism• Oxidation of glucose is shown by the overall

reaction: C6H12O6 + 6O2 6H2O + 6CO2 + 36 ATP + heat

• Glucose is oxidized in three pathways– Glycolysis (cytoplasm) =sugar/lyses (splitting)

– Krebs cycle (matrix of mitochondria)– The electron transport chain (cristae of

mitochondria)

Glycolysis: Phase 1 and 2• Phase 1: Sugar activation

– Two ATP molecules are hydrolyzed providing the energy required to start Glycolysis

– Glucose is into converted into fructose-1,6-diphosphate after 2 hydrolyzed phosphates for each ATP attach to the Glucose.

• Phase 2: Sugar cleavage – Fructose-1,6-bisphosphate is

cleaved into two 3-carbon isomers

• Bishydroxyacetone phosphate( gets converted to G3P)

• Glyceraldehyde 3-phosphate ( G3P) Also known as Phosphglyceraldahyde

Glycolysis: Phase 3

• Phase 3: Oxidation and ATP formation– The 3-carbon sugars are

oxidized (reducing NAD+ forming NADH)

– Inorganic phosphate groups (Pi) are attached to each oxidized fragment

– The terminal phosphates are cleaved and captured by ADP to form four ATP molecules by substrate level phosphorylation.

Glycolysis: Phase 3

• The final products are: – Two pyruvic acid

molecules– Two NADH molecules

(reduced NAD+)– A net gain of two ATP

molecules

Glycolysis Overview

• A three-phase pathway in which:– Glucose is oxidized into pyruvic acid– NAD+ is reduced to NADH – 2 ATP is synthesized by substrate-level

phosphorylation

• Pyruvic acid: – Moves on to the Krebs cycle in an aerobic pathway– Is reduced to lactic acid in an anaerobic environment

Intermediate Step For Krebs Cycle • Occurs in the mitochondria and is

fueled by pyruvic acid • If there is enough O2 present

pyruvic acid is converted to acetyl CoA in three main steps:

1. Oxidation• Hydrogen atoms are

removed from pyruvic acid• NAD+ is reduced to NADH

2. Decarboxylation• Carbon is removed from

pyruvic acid in the form of Carbon dioxide forming acetic acid

3. acetic acid is combined with coenzyme A to form acetyl CoA

Pyruvic Acid → Acetyl CoADuring this step the products

are:– 2 molecules of CO2

– 2 molecules of NADH – 2 molecules of Acetyl CoA

Krebs Cycle

End Products of Krebs Cycle

• 2 acetyl CoA entering the Krebs Cycle will yield:– 6 NADH and 2 FADH2

shuttles H to electron transport chain located on the cristea.

– ATP will be produced by oxidative phosphorylation

– 4 CO2

– 2 ATP via substrate level Phosphorylation.

Electron Transport Chain

Electron Transport Chain (ETC)

• The NADH and FADH2 from glycolysis, acetyl CoA formation and the Krebs cycle are shuttled to the cristea (inner membrane of the mitochondria)

• The cristea has 3 integral membrane proteins that pump protons into the intermembrane space from the matrix. This creates a proton gradient.

• NADH drops a pair of electrons (e-) at the first protein complex while FADH2 goes to the second complex.

• The oxidation of NADH and FADH2 back to NAD and FAD enables these co-enzymes to travel back to the cytoplasm and mitochondria to oxidize another sugar molecule.

Electron Transport Chain

• The e- energize the first protein complex results in 2 protons (H+) from the matrix to be pumped into the intermembrane space.

• The e- are shuttled from the first protein complex to the second one by Co-enzyme Q10

– 2 more protons get pumped out into the intermembrane space.

• Cytochrome (Cyt c) moves the e- to the final protein complex– 2 more protons get pumped out into the

intermembrane space.• This creates a high H+ concentration in the

intermembrane space

ATP Synthase. • The H+ diffuse along their concentration gradient back

into the matrix through the channel protein ATP synthase.

• As the H+ go through the ATP synthase complex energy is created to phosphorylate ADP to make ATP– (Oxidative Phosphorylation) 32-34 ATP produced way

• In order to ensure a H+ gradient O2 must be present in the mitochondria.

• The electrons are transferred to the O2 at the last enzyme complex making O2 especially negative

• O2- atom combined with the H+ that have diffused back

into the matrix from the intermembrane space to form water (H2O)

• O2 must work as the final electron acceptor in the ETC

Lactic Acid Fermentation

• If there is not enough O2

present in the Mitochondria the NADH will return to the cytosol and reduce pyruvic acid to form Lactic acid.

• Lactic acid is another source for ATP

• Lactic acid will be oxidized back to pyruvic acid once O2 is present again

•

Clinical Connection

• There are several forms of Anemia.• Iron deficiency is one of the most common types• Iron is critical for O2 carrying hemoglobin• Iron is also vital for transferring electrons along

the chain. • Symptoms include SOB, fatigue, weakness and

unusual food cravings ( pica)• More common in the elderly• Vitamin C aids in the absorption of iron• Iron is important for energy production!

Glycogen Metabolism• ATP is quickly used after it is formed -- it is not a storage

molecule– extra glucose will not be oxidized, it will be stored

• Glycogenesis -- synthesis of glycogen– stimulated by insulin (average adult contains 450 g) primarily the liver

and Type II muscle fibers.)

• Glycogenolysis -- glycogen glucose– stimulated by glucagon and epinephrine– only liver cells can release glucose back into blood

• Gluconeogenesis -- synthesis of glucose from non-carbohydrates, such as Lactic acid, pyruvic acid, glycerol and amino acids– Takes place mainly in the liver.– Protects the body, especially the brain, from the damaging effects of

hypoglycemia by ensuring ATP synthesis can continue

Lipids• Triglycerides are stored in adipocytes

– constant turnover of molecules every 3 weeks • released into blood, transported and either oxidized or

redeposited in other fat cells

• Lipogenesis = synthesizing fat from other sources– amino acids and sugars used to make fatty acids and

glycerol

• Lipolysis = breaking down fat for fuel– glycerol is converted to PGAL and enters glycolysis– fatty acids are broken down 2 carbons at a time to

produce acetyl-CoA (beta oxidation)

Lipid Metabolism• Glycerol is converted to glyceraldehyde phosphate

– Glyceraldehyde is ultimately converted into acetyl CoA

– Acetyl CoA enters the Krebs cycle • Fatty acids undergo beta oxidation which produces:

– Two-carbon acetic acid fragments, which enter the Krebs cycle

– A 24 carbon fatty acid can produce 12 acetic acids.• 36 total NADH and 12 FADH2 = 120 ATP compared to 32

from glucose• Fats are the best fuel source

Lipid Metabolism

Lipogenesis and Lipolysis

• Excess dietary glycerol and fatty acids undergo lipogenesis to form triglycerides.– Elevated triglycerides is a major cardiac risk factor.

• Lipolysis, the breakdown of stored fat, is essentially lipogenesis in reverse

• Oxaloacetic acid is necessary for the complete oxidation of fat – Fat will only burn in a carbohydrate flame!– Without Carbs fatty acid oxidation is shut down.

– Acetyl CoA is converted into ketones (ketogenesis)

Ketogenesis• Fatty acids catabolized into acetyl groups (by beta-oxidation in

mitochondrial matrix) may – enter citric acid cycle as acetyl-CoA if sugar is present– undergo ketogenesis is the absence if carbohydrates

• metabolized by liver to produce ketone bodies– acetoacetic acid -hydroxybutyric acid– acetone

• rapid or incomplete oxidization of fats raises blood ketone levels (ketosis) and may lead to a pH imbalance (ketoacidosis)

• pH changes can denature many enzymes.• This is very common in uncontrolled diabetics and

people on no carb diets.

Lipogenesis and Lipolysis Pathways

Proteins• Amino acid pool - dietary amino acids plus 100 g of

tissue protein broken down each day into free amino acids

• May be used to synthesize new proteins• As fuel – Only as a last resort

– first must be deaminated (removal of NH2)--what remains is converted to pyruvic acid, acetyl-CoA or part of citric acid cycle

– High protein diets are popular because you may experience rapid weight loss. This is the result of your kidneys pulling more water out of your body to get rite of the excessive nitrogenous wastes

Pathways of Amino Acid Metabolism