Myoglobin and Hemoglobin

• These notes are based on the last lecture of the respiratory system and lectures 12 onwards
• Respiration relies on separate oxygen transport proteins such as myoglobin and hemoglobin

Myoglobin

• Present in tissues and has one subunit
• Can store oxygen (O2) for later use
• Binds to O2 more readily and transports it to the mitochondria
• Less likely to give up O2

Hemoglobin

• Found in red blood cells and has four subunits (two alpha and two beta)
• A tetrameric protein with 2 alpha and 2 beta subunits
• Larger than myoglobin and doesn't readily bind to oxygen

Binding Dynamics

• Globins contain bound prosthetic groups called protoporphyrin 1x, which contain Fe (II) that O2 binds to
• O2 specifically binds to the Fe (II) molecule.
• Shape changes upon binding: the more O2 binds, the less likely the next molecule is to bind

Hemoglobin Dynamics

• The histidine molecule in globins helps stabilize the structure
• Proximal histidine directly contacts the heme group
• Distal histidine contacts the oxygen molecule via hydrogen bonds
• Myoglobin binds to oxygen at low oxygen concentrations and is better for oxygen concentrations

Why Hemoglobin?

• Hemoglobin has a higher partial pressure than myoglobin
• Hemoglobin loses efficacy at lower pressures
• At lower pressures, hemoglobin's binding efficacy decreases, due to the conformational change that occurs
• The more oxygen bound, the more readily the next site will take up another oxygen molecule
• Hemoglobin can be reversed though,
• Not possible with myoglobin due to lacking one binding site

Factors Affecting Oxygen Release

• Hemoglobin releases oxygen through allosteric site manipulation, modified by:
  • pH changes, where increased acidity and CO2 promote extra oxygen release
  • CO2
  • Chloride ions (Cl-)
  • 2,3 BPG (biphosphoglycerate)
• Converted red blood cells reach the lungs (an area with high oxygen), which changes shape to favor oxygen binding and allows CO2 release
• Carbon dioxide lowers hemoglobins affinity

Enzymes and Vitamins

• Pellagra is a vitamin deficiency
• Vitamin C and scurvy allows breakdown and non-production of collagen fibers
• Coenzymes/cofactors near or around active site and allow metabolic processes to occur
• Vitamins are organic molecules required in small amounts for health.
• Can be cofactor sometimes

Vitamin B3

• Vitamin B3 (Niacin/nicotinic acid) is used in body through allowing NAD production and NADP production
• Lack of Niacin, lack of co-factors (NAD+ & NADH) since niacin which are enzyme cofactors.

Pathology of Vitamin B3 Deficiency

• Niacin is necessary in portions due many reasons
  • High turnover of cells (epithelial cells, lining cells)
  • Cells with high energy requirements (nervous system)
• Associated with a poor diet and low in meat
  • Corn used as base starch and doesn't process it properly
  • Higher in tryptophan, niacin precursor.
• Alcohol consumers may not consume other nutrients (poor diet) and lack niacin
  • Poor diet and Lack of enzyme co-factors, collagen fibers, & NAD & NADH

Enzymes Basics

• Enzymes are biological catalysts, are almost all proteins
• Ribozymes are RNA enzymes in peptidyl transferase ure RNA and proteins to complete its job
• Enzymes act upon the substrate and a product is created

Enzyme Catalyst Rules

• Don't get used up
• Speed up reactions that would happen regardless of their presence

Enzyme Classifications

• Oxidoreductases: Catalyze oxidation-reduction reactions, e.g., alcohol dehydrogenase
• Transferases: Transfer one functional group to the other, e.g., Hexokinase and NAD+
• Hydrolases: Cleaves molecules with the use of water (make new product)
• Lysases: Cleavage of a bond without the use of water
• Isomerases: Rearrangement of structures already present on the substrate.
• Ligases: Catalyzation of 2 molecules together

Enzyme Mechanics

• Amylase is a family of enzymes that breaks down starch into smaller components using water
• In the initial stages of glycolysis, phosphoglycerate enzyme rearranges the molecule using no water or additional substrates

Enzyme Reaction Factors

• Substrate enters and leaves as products with enzymes
• The rate depends on concentration and is determined by products produced/substrate consumed/unit time
• The concentration of substarate = accurate
• As the [A] decreases, the rate decreases and is a first-order reaction

Reaction Dynamics

• In first-order reactions, the fastest rate is at the beginning
• Vitamins = Organic molecules -required -in small amounts
• Metal cofactors : Reactions active sites involved: oxidation, reduction reactions are used; Facilitates NAD+ Binding

What affects Reaction Rate?

• Order of reaction (first & second) and components involved
• Concentration of reactants; to allow for substrate in transition state

Temperature

• Enzymes don't add much energy to system, Enzymes allow substances rapid transition from higher free energy to lower free energy/
  • Substrate binds to active site: charge complementarity
  • More charge complementarity the substrate & substrate specific

Reaction Rates

• Enzyme driven vs non-enzymatically driven processes
• rates of reaction without enzyme depend on temperature, PH and bond strength
  • eg. Hydrolysis of peptide bonds occurs at 1x10^13 higher rates
• enzymes do not add additional energy

Acetylcholine

• Excitatory neurotransmitter in the peripheral nervous system
• some parts of central nervous system
• They facilitate communication between nervous system & musculature
• Released from nerve cell, Stimulates muscle cell through openings of sodium channels (relax and contract muscle)

Acetylcholinesterase

• Is a hydrolase and balances Ach amounts in the neuromuscular junction
• Break ach into acetate and choline
• Balances Ach amounts in the neuromuscular Junction (NMT)- since we don't need high amounts
• Too much Ach in NMJ causes sweating; diarrhea and respiratory arrest.

Alzheimer's and Inhibitors

• Ach esterase Inhibitors improve memory and function in patients since less cholinesterase
• increasing the amount and acetyl choline available to remaining cells has a therapeutic effect.
• side effects and effective in alzehiemer
• Sarin gas and toxin are irreversible inhibitors

Enzyme Kinetics and Factors

• Steady state: 4 state: steady, enzyme, substrate, product
• binds irreversibly to Ach esterase, making it is an Irreversible inhibitor
• it can bind enzyme for it will be used or needed

Enzyme Regulation

• Enzyme - substrate interactions - is when enzymes are added to solution that has enough substrate, ES complex forms

Km and Action

• Lower the Km value the more ability you have to attach to ES
• V = Max then reaction 4 enzyme for velocity
• V= Rate of free Enzyme

Enzyme Rate

• decrease rate
• affect on binding is helpful to know, examine the enzyme
• Difference in km, km affects enzyme's catalytic ability, the enzymes catalytic activity changes, changing

Enzyme types and action

• Enzymes action specific
• bind to or without enzyme and is a noncompetitive inhibitors

Feedback control

• Helps create an stable eniroment
• Helps the enzyme create to decrease it's own production

Covalent Modification

• Used with bonds that are difficult to break -Requires phosphate group binding to speed up process
  • Causes many inactive enzymes to become activated by others. in pathway

Metabolism of Food Products

• Main biological macromolecules: Fats, carbohydrates, protein
• Main digestive organs: Stomach, small/large intestines

Carbonhydrate Digestion

• initial breakdown starts at mouth and brush borders intestine
• secondary breakdown are enzymes in small intestine - pancreatic enymes - protein digestive actions

Protein Digesteion

• stomach and intestines involved and broken down to small components
• Small component has low PH and water soluability

Fat Digestion

• small intestine and emulcification involved with BILE and enzymes breaking it down
• 5 + 6 M is small intestine length
• Duodenum - connects to small intestine

Metabolism: Beginnings

• monomers converted into simpler organic compounds
• degradation of simple compounds into energy and simple, non-organic compounds

What the Components Do

• small intestine produces
• brush borders contain villi
• has colonmar cells, supporting organs necessary for chyme production
• reabsorbs ions & releases water
• Chyme=digested food in digestive tract

Liver

• bile protection= vitamin and nutrients

Pancreas

• exo/endocrine functions with digestion.
• includes: proteases, amylase, lipases
• Trypsin breaks down collagen

Energy Factors

• Metabolic pathways: work from biomolecules in a catabolic or anabolic state with oxidations & reactions
• Nucleophile: Has e to donate
• Electrophile: has space to accept e to form a bond.
• Carbon rich group are polar with carbons positiverly charged

Factors to Reaction

• Nuceophilic Substitution.
• Nuceophilic addition:
• Cabonyl addition
• Elimation
• Oxidation/reduction from reaction

Bioreactions

• product degradation and oxidation from product,
• Or is reduction reactions and oxogyn excellect electron
• carries: NAD/FAD + phosphorylation reactions (Atp + ADPH)

Energy Factors

• almost all living cells use glucosis
• control of metabolism in liver and intestines
• requires enzymes and diff states - study

Sugar

• glucose intolerance and insulin resistance
• Isotonic solutions

Glucose

• glycolysis through a cycle
  • Needs molecules of phosphoral group to group energy investiture
  • and pyruvate synthetis

Metabolic cycle

• investment and energy return occurs

Enzymes role in glycolysis

• addition of phosphoryl group to chain and traps.