Glycolysis, Krebs Glycolysis, Krebs Cycle, and other Cycle, and other Energy-Releasing Energy-Releasing

PathwaysPathways

stages of cellular stages of cellular respirationrespiration

glycolysis glycolysis Kreb’s cycle Kreb’s cycle

electron electron transport/oxidative transport/oxidative

phosphorylationphosphorylation

What is Cellular What is Cellular Respiration?Respiration?

A process in which the energy in glucose is A process in which the energy in glucose is transferred to ATP transferred to ATP

Cells use ATP to supply their energy needsCells use ATP to supply their energy needs

Cellular RespirationCellular Respiration Glucose is Glucose is oxidizedoxidized (releasing energy) (releasing energy)

and oxygen is and oxygen is reducedreduced to form water to form water The carbon atoms of the sugar molecule The carbon atoms of the sugar molecule

are released as are released as carbon dioxidecarbon dioxide (CO (CO22)) The complete breakdown of glucose to The complete breakdown of glucose to

carbon dioxide and water requires two carbon dioxide and water requires two major steps:major steps: 1)1)Glycolysis - produces two ATPGlycolysis - produces two ATP2)2)Aerobic respiration - thirty-four more ATP Aerobic respiration - thirty-four more ATP – In the absence of oxygen, fermentation In the absence of oxygen, fermentation

reactions produce alcohol or reactions produce alcohol or lactic acidlactic acid but no but no additional ATPadditional ATP

GLYCOLYSISGLYCOLYSIS glyco = sugar; lysis = breakingglyco = sugar; lysis = breaking

GoalGoal: breaks glucose down to form two : breaks glucose down to form two pyruvates (main pathway) pyruvates (main pathway)

WhoWho: all life on earth performs : all life on earth performs glycolysis glycolysis

WhereWhere: in the cytosol : in the cytosol Glycolysis produces 4 ATP's and 2 Glycolysis produces 4 ATP's and 2

NADH, but uses 2 ATP's in the process NADH, but uses 2 ATP's in the process for afor a netnet of 2 ATP and 2 NADH of 2 ATP and 2 NADH

Biomedical importanceBiomedical importanceDeficiency of enzymes of glycolysis Deficiency of enzymes of glycolysis

can lead to diseasescan lead to diseases Hemolytic anemiasHemolytic anemias Fatigue (skeletal muscles) Fatigue (skeletal muscles) IschemiaIschemia Hypermetabolism in cancer cachexiaHypermetabolism in cancer cachexia Lactic acidosisLactic acidosis

The First Stage of The First Stage of GlycolysisGlycolysis

1. glucose is phosphorylated, converted to fructose, and

then fructose is phosphorylated

2. Produces 2 molecules; dihydroxyacetone phosphate and Glyceraldehyde-3-Phosphate

HexokinaseGlucokinase

Phosphohexose isomerase

Phosphofructokinase

Aldolase

Phosphotriose isomerase

The Second Stage of The Second Stage of GlycolysisGlycolysis

1. Gly-3-P is oxidized by NAD+ and phosphorylated with Pi producing 1,3-bisphosphoglycerate and NADH

2. Phosphates are transferred to ADP producing

ATP in two different steps

Pyruvate kinaseEnolas

e

Phosphoglycerate kinase

Phosphoglycerate kinase

Phosphoglycerate mutase

3. Final product is 2 x (Pyruvate + 2 ATP + NADH)

Final stepsFinal steps NADH must be NADH must be

oxidized to NADoxidized to NAD++ ==> depend upon ==> depend upon whether Owhether O22 is is availableavailable

ANAEROBICANAEROBIC– Pyruvate is reduced Pyruvate is reduced

by NADH to Lactate by NADH to Lactate and NADand NAD++

AEROBICAEROBIC– Pyruvate transported Pyruvate transported

to mitochondrion to mitochondrion

(enol) (Keto)

Anaerobic RespirationAnaerobic Respiration Goal: to reduce pyruvate, thus generating NADGoal: to reduce pyruvate, thus generating NAD++ Where: the cytoplasm Where: the cytoplasm Why: in the absence of oxygen, it is the only Why: in the absence of oxygen, it is the only

way to generate NADway to generate NAD++ and ADP and ADP

Alcohol Fermentation

• Occurs in yeasts in many bacteria •The product of fermentation, alcohol, is toxic to the organism

Anaerobic RespirationAnaerobic Respiration Lactic Acid Lactic Acid

FermentationFermentation - - occurs in humans occurs in humans and other mammals and other mammals – The product of Lactic The product of Lactic

Acid fermentation, Acid fermentation, lactic acid, is toxic to lactic acid, is toxic to mammals mammals

– This is the "burn" felt This is the "burn" felt when undergoing when undergoing strenuous activity strenuous activity

Aerobic RespirationAerobic Respiration

The process by which a cell uses OThe process by which a cell uses O22 to "burn" molecules and release to "burn" molecules and release energy energy

The reaction: The reaction:

CC66HH1212OO66 + 6O + 6O22 >> 6CO >> 6CO22 + 6H + 6H22O O NADNAD++ and FAD carry electrons to the and FAD carry electrons to the

electron transport systemelectron transport system

The Citric Acid CycleThe Citric Acid Cycle

Tricarboxylic Acid (TCA) Cycle or the Tricarboxylic Acid (TCA) Cycle or the Krebs CycleKrebs Cycle

GoalGoal: take pyruvate and put it into the : take pyruvate and put it into the Krebs cycle, producing NADH and FADHKrebs cycle, producing NADH and FADH22

: : provide substrate for respiratory provide substrate for respiratory chainchain

WhereWhere: the mitochondria : the mitochondria There are two steps There are two steps

(1) The Conversion of Pyruvate to Acetyl CoA (1) The Conversion of Pyruvate to Acetyl CoA

(2) The Krebs Cycle proper (2) The Krebs Cycle proper

The Citric Acid CycleThe Citric Acid Cycle

All of Carbons, Hydrogens, and Oxygen All of Carbons, Hydrogens, and Oxygen in pyruvate end up as in pyruvate end up as COCO22 and H and H22OO

The Krebs cycle plus the conversion of The Krebs cycle plus the conversion of pyruvate produces;pyruvate produces;– 2 ATP's2 ATP's– 8 NADH's8 NADH's

– and 2 FADHand 2 FADH22's 's

………….. per glucose molecule .. per glucose molecule

B vitamins essential in the B vitamins essential in the Citric acid cycleCitric acid cycle

RIBOFLAVIN - RIBOFLAVIN - flavin adenine dinucleotide flavin adenine dinucleotide (FAD)(FAD)– A cofactor for succinate dehydrogenaseA cofactor for succinate dehydrogenase

NIACIN - NIACIN - nicotinamide adenine dinucleotide nicotinamide adenine dinucleotide (NAD)(NAD)– Electron acceptor for isocitrate dehydrogenase, Electron acceptor for isocitrate dehydrogenase,

-ketoglutarate dehydrogenase, and malate -ketoglutarate dehydrogenase, and malate dehydrogenasedehydrogenase

THIAMIN (Vitamin BTHIAMIN (Vitamin B11) – ) – thiamine thiamine diphosphatediphosphate– Coenzyme for decarboxylation in the Coenzyme for decarboxylation in the --

ketoglutarate dehydrogenase reactionketoglutarate dehydrogenase reaction PANTOTHENIC ACID - PANTOTHENIC ACID - coenzyme A (CoA) coenzyme A (CoA)

– The cofactor attached to the “active” carboxylic acid The cofactor attached to the “active” carboxylic acid residues such as acetyl-CoA and succinyl CoAresidues such as acetyl-CoA and succinyl CoA

Kreb’s cycle animationKreb’s cycle animation

http://www.science.smith.edu/http://www.science.smith.edu/departments/Biology/Bio231/departments/Biology/Bio231/krebs.htmlkrebs.html

The Conversion of Pyruvate to The Conversion of Pyruvate to Acetyl CoA for Entry Into the Acetyl CoA for Entry Into the

Krebs CycleKrebs Cycle

Kreb’s cycle summaryKreb’s cycle summary

When acetyl CoA attaches to a C4 molecule in the Krebs cycle, the Coenzyme A is releasedTwo acetyl CoA molecules are consumed to produce 4 CO2, 2ATP, 6 NADH and 2 FADH2

Kreb’s cycle summaryKreb’s cycle summary

ATP is produced by substrate level phosphorylation– production of ATP

using energy from other high-energy compounds but without the use of the electron transport system in the mitochondria

SummarySummary

Electron Transport and Electron Transport and Oxidative PhosphorylationOxidative Phosphorylation

Goal Goal : to break down NADH and FADH: to break down NADH and FADH22, pumping H, pumping H++ into into the outer compartment of the mitochondria the outer compartment of the mitochondria

Where Where : the mitochondria : the mitochondria

Electron Transport SystemElectron Transport System

It consists of a series of carrier molecules which It consists of a series of carrier molecules which pass electrons from a high-energy compound to pass electrons from a high-energy compound to a final low-energy electron acceptor a final low-energy electron acceptor

Energy is released during these oxidation-Energy is released during these oxidation-reduction reactions to produce ATPreduction reactions to produce ATP

NADH and FADHNADH and FADH22 are used to produce ATP as are used to produce ATP as electrons are passed from one carrier to electrons are passed from one carrier to anotheranother

Eventually the electrons combine with Eventually the electrons combine with hydrogen ions and oxygen (reduction) to form hydrogen ions and oxygen (reduction) to form waterwater

Electron Transport SystemElectron Transport System

ETS creates a gradient which ETS creates a gradient which is used to produce ATPis used to produce ATP

ATP is generated as HATP is generated as H++ moves down its concentration moves down its concentration gradient through a special gradient through a special enzyme called ATP synthaseenzyme called ATP synthase

OxygenOxygen is the final electron is the final electron acceptoracceptor

The low-energy electrons that The low-energy electrons that emerge from the electron emerge from the electron transport system are taken transport system are taken up by Oup by O22. The negatively . The negatively charged oxygen molecules charged oxygen molecules take up protons from the take up protons from the medium and form water (2Hmedium and form water (2H++ + 2e- + ½ O+ 2e- + ½ O22 → → HH22O) O)

Electron Transport Electron Transport Phosphorylation typically Phosphorylation typically produces 32 ATP's produces 32 ATP's

Electron Transport SystemElectron Transport System

Total ATP yield per glucoseTotal ATP yield per glucoseConversionsConversions NADHNADH produced in the cytoplasm produces two produced in the cytoplasm produces two ATPATP by the by the

electron transport systemelectron transport system NADH produced in the mitochondria produces three ATP.NADH produced in the mitochondria produces three ATP. FADHFADH22 adds its electrons to the electron transport system at a adds its electrons to the electron transport system at a

lower level than NADH, so it produces two ATP.lower level than NADH, so it produces two ATP.

GlycolysisGlycolysis– 2 ATP2 ATP– 2 NADH (= 4 ATP; these are converted to ATP in the 2 NADH (= 4 ATP; these are converted to ATP in the

mitochondria during cellular respiration)mitochondria during cellular respiration)

Formation of Acetyl CoAFormation of Acetyl CoA– 2 NADH (= 6 ATP)2 NADH (= 6 ATP)

Krebs CycleKrebs Cycle– 6 NADH (= 18 ATP)6 NADH (= 18 ATP)– 2 FADH2 FADH22 (= 4 ATP) (= 4 ATP)– 2 ATP2 ATP* 12 ATP’s are yielded per turn (18 + 4 + 2 = 24/2 =12)* 12 ATP’s are yielded per turn (18 + 4 + 2 = 24/2 =12)

PathwayPathway Substrate-Substrate-LevelLevelPhosphorylatiPhosphorylationon

OxidativeOxidativePhosphorylatiPhosphorylati

onon

TotalTotalATPATP

GlycolysisGlycolysis 2 ATP2 ATP 2 NADH = 4 - 6 2 NADH = 4 - 6 ATP* ATP*

* In animals* In animals

6 - 8*6 - 8*

CoACoA 2 NADH = 6 ATP 2 NADH = 6 ATP 66

Krebs Krebs CycleCycle

2 ATP2 ATP 6 NADH = 18 6 NADH = 18 ATPATP

2 FADH2 FADH22 = 4 = 4 ATP ATP

2424

TOTALTOTAL 4 ATP4 ATP 32 ATP32 ATP 36 – 3836 – 38

Beta OxidationBeta Oxidation Fats consist of a glycerol backbone with two or Fats consist of a glycerol backbone with two or

three fatty acids connected to it three fatty acids connected to it The body absorbs fats and then breaks off the The body absorbs fats and then breaks off the

fatty acids from the glycerol fatty acids from the glycerol Glycerol is converted to glyceraldehyde Glycerol is converted to glyceraldehyde

phosphate, an intermediate of glycolysis phosphate, an intermediate of glycolysis The fatty acids are broken down into two-carbon The fatty acids are broken down into two-carbon

units which are then converted to acetyl CoA units which are then converted to acetyl CoA – An eight-carbon fatty acid can produce 4 acetyl CoA's An eight-carbon fatty acid can produce 4 acetyl CoA's – Each acetyl CoA is worth 12 ATP's (3 NADP, 1 FADH2, 1 Each acetyl CoA is worth 12 ATP's (3 NADP, 1 FADH2, 1

ATP) ATP) – Therefore, this short fatty acid is worth 48 ATP's, a fat Therefore, this short fatty acid is worth 48 ATP's, a fat

with three chains of this length would be worth 144 with three chains of this length would be worth 144 ATP's! ATP's!

– This is why fats are such a good source of energy, and This is why fats are such a good source of energy, and are hard to lose if you want to lose weight are hard to lose if you want to lose weight

Other Uses for Molecules Other Uses for Molecules used in Glycolysis and the used in Glycolysis and the

Krebs CycleKrebs Cycle Not all of the molecules that enter Not all of the molecules that enter

Glycolysis and the Krebs Cycle are Glycolysis and the Krebs Cycle are used for energy used for energy

Some are used to synthesize fats, Some are used to synthesize fats, nucleotides, amino acids, and other nucleotides, amino acids, and other biologically important molecules biologically important molecules