Kaplan MCAT Biology 03

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Kaplan MCAT Biology 04

Cellular Metabolism

- the sum total of all chemical reactions that take place in a cell
- either anabolic (require energy) or catabolic (release energy)

Autotrophic

- green plants
- convert sunlight into bond energy stored in the bonds of organic compounds (glucose) in the anabolic process of photosythesis
- don't need an exogenous supply of organic compounds

Heterotrophic

- obtain energy catabolically
- break down organic nutrients that must be ingested

Net reaction of photosynthesis

6CO₂ + 2H₂O + energy --> C₆H₁₂O₆ + 6O₂

Energy Carriers

- molecular carriers used by the cell to shuttle energy between reactions
- ATP, NAD⁺, FAD

ATP

- adenosine triphosphate
- cell's main energy currency
- synthesized during glucose catabolism
- composed of nitrogenous base adenine, sugar ribose and three weakly linked phosphate groups
- energy of ATP is stored in these covalent bonds (high-energy bonds)

ADP

- adenosine diphosphate
- Pi: inorganic phosphate
- ATP --> ADP + Pi + 7 kcal/mole
- the 7 kcal/mole provides energy for endergonic/endothermic reactions like muscle contraction, motility and active transport across plasma membranes

AMP

- adenosine monophosphate
- PPi: phyrophosphate
- ATP --> AMP + PPi + 7 kcal/mole

Carrier Coenzymes

- NAD⁺, FAD, NADP⁺
- transport the high energy electrons of the hydrogen atoms to a series of carrier moelcules on the inner mitochondrial membrane (electron transport chain)

NAD⁺

nicotinamide adenine dinuclotide

FAD

flavin adenine dinucleotide

NADP⁺

- nicotinamide adenine dinucleotide phosphate
- the reduced form, NADPH, is found in plant cells only

Oxidation

- loss of an electron
- NAD⁺, FAD, NADP⁺ are referred to as oxidizing agents because they cause other molecules to lose electrons and undergo oxidation (while they're reduced NADH, FADH₂, NADPH)

Reduction

- gain of electrons

Glucose Catabolism

occurs in two stages:
a) glycolysis
b) cellular respiration

Glycolysis

- series of reactions that lead to the oxidative breakdown of glucose into two molecules of pyruvate, the production of ATP and reduction of NAD⁺ into NADH
- occurs in cytoplasm
- mediated by specific enzymes

Glycolytic Pathway

- fructose 1,6-diphosphate is split into dihydroxyacetone and glyceraldehyde 3-phosphate (PGAL)
- dihydroxyacetone is isomerized into PGAL
- two molecules of PGAL is formed per molecule of glucose
- 1 glucose = 2 pyruvate
- net production of 2 ATP/mole of glucose (4 generated, 2 used up)

Substrate Level Phosphorylation

- ATP synthesis is directly coupled with the degradation of glucose without the participation of an intermediate molecule like NAD⁺

Net Reaction for Glycolysis

glucose + 2ADP + 2Pi + 2 NAD⁺

-->

2 pyruvate + 2ATP + 2NADH + 2H⁺ + 2H₂O

Fate of Pyruvate

- anaerobic: pyruvate is reduced through fermentation
- aerobic: pyruvate is further oxidized during cell respiration in mitochondria

Fermentation

- regeneration NAD⁺ to continue glycolysis without O₂
- reduce pyruvate to ethanol or lactic acid
- fermentation produces only 2 ATP per glucose molecule

Alcohol Fermentation

- occurs in yeast and bacteria only
- pyruvate produced in glycolysis is decarboxylated to acetaldehyde, then reduced by NADH in step 5 of glycolysis to yield ethanol
- pyruvate --> acetaldehyde --> ethanol

Lactic Acid Fermentation

- occurs in certain fungi and bacteria and in human muscle cells during strenuous activity
- happens when oxygen supply to muscle cells lags behind the rate of glucose catabolism
- pyruvate generated is reduced to lactic acid, which can lower blood pH if accumulated, eventually becomes muscle fatigue
- oxygen debt: the amount of oxygen needed to oxidize lactic acid back to pyruvate and enters cellular respiration

Cellular Respiration

- most efficient catabolic pathway to harvest energy stored in glucose
- occurs in mitochondrion and catalyzed by reaction specific enzymes
- produces 36-38 ATP
- aerobic, O₂ acts as the final acceptor of electrons that are passed from carrier to carrier during the final stage of glucose oxidation
- three stages: pyruvate decarboxylation, citric acid cycle and electron transport chain

Pyruvate Decarboxylation

- pyruvate formed during glycolysis is transported from the cytoplasm into the mitochondrial matrix where it is carboxylated (lost a CO₂), and the remaining acetyl group is transfered to coenzyme A to form acetyl CoA.
- in process, NAD⁺ is reduced to NADH
- pyruvate + coenzyme A -- acetyl CoA

The Citric Acid Cyle (TCA Cycle)

- known as the Krebs cycle or the tricarboxylic acid cycle (TCA cycle)
- begins when the two carbon acetyl group from acetyl CoA combines with oxaloacetate, a four carbon molecule, to form the six carbon citrate
- 2CO₂ are released, oxaloacetate is regenerated to use for another turn of the cycle
- 1 cycle = 1 ATP produced by substrate level phosporylation via GTP intermediate
- electrons are transferred to NAD⁺ and FAD, generating NADH and FADH₂, which transport electrons to electron transport chain

The Citric Acid Cyle continued

- electrons are transferred to NAD⁺ and FAD, generating NADH and FADH₂, which transport electrons to electron transport chain, where ATP is produced via oxidative phosporylation
- each molecule of glucose = 2 pyruvates
2x3 NADH --> 6 NADH
2x1 FADH₂ --> 2 FADH₂
2x1 GTP (ATP) --> 2 ATP

Oxidative Phosphorylation

- ATP is produced when high energy potential electrons are transferred from NADH and FADH₂ to oxygen by a series of carrier molecules located in the inner mitochondrial membrane
- as the electrons are transferred from carrier to carrier, free energy is released
- later this energy is used to form ATP

Net reaction of Citric Acid Cycle per glucose molecule

2 Acetyl CoA + 6 NAD⁺ + 2 FAD + 2 ATP + 2Pi + 4H₂O

-->

4 CO₂ + 6 NADH + 2 FADH₂ + 2 ATP + 4 H⁺ + 2 CoA

Electron Transport Chain (ETC)

- a complex carrier mechanism located on the inside of the inner mitochondrial membrane
- two parts: electron transfer and ATP generation + the proton pump

Cytochromes

- most of the molecules of the ETC
- electron carriers that resemble hemoglobin in structure of their active site
- functional unit contains a central iron atom, which is capable of undergoing a reversible redox reaction

FMN (flavin mononuclotide)

- first molecule of the ETC
- reduced when it accepts electrons from NADH, therefore oxidizing NADH to NAD⁺

Cytochrome a₃

- last carrier of the ETC
- passes its electron to the final eectron acceptor, O₂
- in addition, O₂ picks up a pair of hydrogen ions from the surrounding medium and forms water
- 2H⁺ + 2e⁻ + ½ O₂ --> H₂O

ETC without )₂

- without oxygen, ETC becomes backlogged with electrons and NAD⁺ can't be regenerated to continue glycolysis without lactic acid fermentation occuring
- Cyanide and dinitrophenol works the same way.
- Cyanide blocks the transfer of electrons from Cytochrome a₃ to O₂
- Dinitrophenol uncouples the electron transport chain from the proton gradient established across the inner mitochondrial membrane

Electron Carriers

- categorized into three large protein complexes:
a) NADH dehydrogenase
b) the b-c₁ complex
c) cytochrome oxidase

ATP Generation and the Proton Pump

- there are energy losses as electrons are transferred from one complex to the next, this energy is then used to synthesize 1 ATP per complex
- since we have 3 complexes, we generate 3 ATP
- NADH delivers its electrons to NADH dehydrogenase complex, so for each NADH = 3 ATP
- FADH₂ bypasses the NADH dehydrogenase complex and delivers directly to carrier Q (ubiquinone), which is between complex 1 and 2, so each FADH₂ = 2 ATP

Proton Gradient

- as NADH passes its electrons to the ETC, free H⁺ are released and accumulate in mitochondrial matrix
- ETC pumps these ions out of the matrix, across the inner mitochondrial membrane and into intermembrane space at each of the three protein complexes
- the continuous translocation of H⁺ creates a positively charged acidic environment in the intermembrane space

Proton-Motive Force

- from proton gradient
- drives H+ back across inner membrane and into the matrix
- membrane is impermeable to ions, so H⁺ must flow through specialized channels provided by enzyme complexes called ATP synthetases
- as H⁺ pass through ATP synthetases, energy is released to allow for the phosphorylation of ADP to ATP
- oxidative phosphorylation: coupling of oxidation of NADH with phosphorylation of ADP

Glucose Catabolism - event and location

Event --> Location

glycolysis -- cytoplasm
fermentation -- cytoplasm
pyruvate to acetyl CoA -- mitochondrial matrix
TCA cycle -- mitochondrial matrix
ETC - inner mintochondrial matrix

Review of Glucose Catabolism

- Net amount of ATP = ATP by substrate level phosphorylation + ATP by oxidative phosphorylation
- Substrate level = 1 glucose = ATP from glycolysis + (1 ATP x 2 turn of Citric Acid Cycle) ---> 4 ATP
- Oxidative = 32 ATP
- Total = 36 ATP

Alternate Energy Sources

- when glucose supplies run low, the body uses these (in order): carbohydrates, fats and proteins
- these are first converted to either glucose or glucose intermediates, which can be degraded in the glycolytic pathway and TCA cycle

Carbohydrates

- disaccharides are hydrolyzed into monosaccharides
- then converted into glucose or glycolytic intermediates
- glycogen in the liver can be converted into glucose 6-phosphate, a glycolytic intermediate

Fats

- stored in adipose tissue in the form of triglyceride
- when needed, they are hydrolyzed by lipases to fatty acids and glycerol, and are carried by the blood to other tissues for oxidation
- glycerol can be converted into PGAL
- a fatty acid must be "activated" first in the cytoplasm, this requires 2 ATP
- on active, it is transorted into mitochondrion and taken through a series of "beta-oxidation cycles" that convert it into two carbon fragments, then converted to acetyl CoA, which enter TCA cycle.
- each round of beta oxidation generates 1 NADH and 1 FADH₂
-fats yield the most ATP per gram

Proteins

- the body degrades amino acids only when there isn't enough carbs available
- most amino acids undergo a transamination reaction where they lose an amino group to form an alpha-keto acid
- carbon atoms of most amino acids are converted into acetyl CoA, pyruvate or one of the intermediates of the citric acid cycle

Metabolic Map

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