CELL RESPIRATION & METABOLISM 2 Dr. Perkins

OVERVIEW

OVERALL EQUATION Aerobic Cellular respiration

ATP forms in the Mitochondrion

How does ATP form in the mitochondrion? STEP 1: Formation of Acetyl CoA. After one 6-carbon glucose molecule breaks down into two 3-carbon pyruvate molecules, pyruvate enters the mitochondrion. A single carbon is removed and breathed out of the body as carbon dioxide. The other two carbons attach to a molecule called Coenzyme A, forming Acetyl Coenzyme A (Acetyl CoA) When carbon dioxide is formed, energy is released in the form of electrons that are captured by NAD to form NADH + H+. Yield 1: NADH per pyruvate.

The Krebs Cycle PRODUCTS: 3 NADH 1 FADH2 1 ATP (per Pyruvate) WASTE PRODUCTS: 2 carbon dioxide

The Complete Citric Acid Cycle

Electron Transport Chain 1. NADH or FADH2 bring electrons to the membrane

Electron Transport Chain 2. In a series of redox reactions, electrons are transferred from one complex to the next.

Electron Transport Chain 3. Some of the energy drives proton pumps.

Electron Transport Chain: Chemiosmosis 4. Protons accumulate in the intermembrane space, and they diffuse through ATP synthase driving the synthesis of ATP. This is known as chemiosmosis.

Electron Transport Chain: Chemiosmosis 5. Oxygen attracts the electrons at the end of the chain and is converted to water.

Electron Transport Chain Electrons are transferred to oxygen (oxidative) ATP is formed (phosphorylation of ADP) Oxidative phosphorylation

Detailed Accounting

Free Radicals Free radicals – molecules with unpaired electrons E.g. oxygen – when it receives electrons in the ETC, sometimes oxygen free radicals known as reactive oxygen species: Superoxide free radicals Other free radicals: Hydroxyl free radicals Nitric oxide free radicals Lead to diseases, such as atherosclerosis. Antioxidants – molecules that scavenge free radicals; protect the body

Interconversion of Glucose and Glycogen

Glycogen Long chain polysaccharide Stored in liver and muscle Storage form of carbohydrates. Glucose storage would result in high osmotic pressure Glycogenesis – glucose  glycogen Actually a two step process: glucose  G6P  G1P  (glycogen synthase) Glycogen Glycogenolysis – glycogen  (glycogen phosphorylase) G1P  G6P (cannot leak out of the cell). Liver contains glucose-6-phosphatase; catalyzes G6P  glucose (gluconeogenesis)

Glycogenesis Glycogenolysis Glycogen synthase Glycogen phosphorylase Glucose from glycogen is in the form glucose 1-phosphate, so cannot leave muscle or heart cells. Glucose-6-phosphatase Glucose from glycogen is in the form of glucose 1-phosphate, so cannot leave most cells.

Cori Cycle Cori Cycle – the delivery of blood lactic acid to the liver for conversion into glucose. Gluconeogenesis – the conversion of G6P, and other non-carb molecules

METABOLISM OF LIPIDS

Glucose is Converted to Glycogen or FAT When ATP levels are high When more food is taken into the body than is needed to meet energy demands Acetyl CoA can also be converted to other molecules (next slide).

Acetyl CoA is a branchpoint  Lipogenesis – the addition of fatty acids to glycerol

Why is fat our long term energy storage molecule? 1 g of fat = 9 kcal of energy 1 g of CH2O or protein = 4 kcal of energy WHITE FAT (White adipose tissue) - where most of our triglyceride are stored. Adipocytes LIPASE carries out lipolysis, the breakdown of triglycerides into fatty acids and glycerol. Free glycerol goes to the liver, where it is used to make glucose, which is sent to the blood What happens to fatty acids?

β-oxidation The process by which energy is released from free fatty acids Enzymes remove acetic acid (2 carbons) from ends of fatty acids Acetic acid is added to CoA  AcetylCoA The β-carbon becomes oxidized. Electrons are donated to NAD and FADH2 carriers for ATP synthesis A single 16-carbon-long fatty acid yields 108 ATP

1) Fatty acid is added to CoA β-oxidation 1) Fatty acid is added to CoA 2) Hydrogen is removed  added to FAD  FADH2 FADH2 donates e- to make ATP 3) OH from H2O added to β carbon 4) Reduction of NAD  NADH NADH donates e- to make ATP 5) Bond between alpha and β carbons breaks

BROWN ADIPOSE TISSUE Involved in thermogenesis (heat production) Especially in newborns, but also in adults. How does it generate heat?

UCP-1: an uncoupling protein Norepinephrine causes brown fat to form UCP-1 UCP-1 “uncouples” electron transport chain H+ leak out of inner mitochondrial membrane Less ATP is formed Stimulates β-oxidation, which generates heat.

KETONE BODIES Can provide energy! Times of high fat breakdown: (as in dieting, starvation, or diabetes)  fatty acids build up in blood Liver cells convert fatty acids  acetyl CoA for energy, but also into ketone bodies. Water-soluble molecules that circulate in the blood. Ketosis – build up of ketone bodies in blood During fasting Fruity odor in breath (acetone) Acetone has a fruity odor in breath

CONDITIONS RELATED TO KETONE BODIES  Ketoacidosis: too many ketone bodies in the blood affects buffer system  serious consequences Ketonuria: accumulation of ketone bodies in the urine. When ketone is excreted, sodium is excreted along with it. Leads to excessive urination, producing severe dehydration These two conditions together can lead to coma, death.

METABOLISM OF PROTEINS

Nitrogen Balance NORMAL Ingest = excrete POSITIVE Take in more than excreted Can be used for energy NEGATIVE Excrete more than is taken in Catabolic

PROTEIN Provides nitrogen; replace other proteins Excess amino acids: used for energy converted into carbohydrates or fat. Bodies make 12 of the 20 amino acids. 8 of them (9 in children) come from the diet (essential).

Transamination New amino acids are formed in the body Amine group is transferred from one amino acid to form another Catalyzed by transaminases Pyruvic acid and several citric acid cycle intermediates (called keto acids) can be converted to amino acids by adding an amine group (NH2). Usually obtained from other amino acids Requires vitamin B6 as a coenzyme Each transamination requires a specific enzyme

aspartate transaminase Transamination aspartate transaminase Pyruvic acid and several citric acid cycle intermediates (called keto acids) can be converted to amino acids by adding an amine group (NH2). Usually obtained from other amino acids Requires vitamin B6 as a coenzyme Each transamination requires a specific enzyme Alanine transaminase

Oxidative Deamination In conditions of excess amino acids Amino acids give their NH3 to α-ketoglutarate, and glutamic acid is formed Glutamic acid gives its NH3 to CO2 Remaining keto acids can form glucose (gluconeogenesis) If there are more amino acids than needed, the amine group from glutamic acid can be stripped and excreted as urea in the urine. Oxidative deamination sometimes forms pyruvic acid or another citric acid cycle intermediates. These can be used to make energy or converted to glucose or fat. The formation of glucose from amino acids is called gluconeogenesis and occurs in the Cori cycle. The main substrates are 3-carbon molecules – alanine, lactic acid, and glycerol

Different Ways That Amino Acids are Used for Energy

Glycogen, Fat, and Protein Interconversion of Glycogen, Fat, and Protein Glucose and ketone bodies come from the liver Lactic acid and amino acids come from muscle Fatty acids come from adipose tissue Lactic acid and amino acids come from muscle Fatty acids come from adipose tissue