CH 6 How does the body generate ATP

Adenosine Triphosphate (ATP)

body's energy currency
-powers all necessary cellular processes which require energy

how is energy stored

in bonds of ATP (7.3kcal/mol)
-bonds are then broken and energy transferred to do work

ADP (adenosine diphosphate)

forms when ATP joins with water
-outermost phosphate is released

ATPase

enzyme that catalyzes hydrolysis of ATP

Adenosine monophosphate (AMP)

formed when another Pi is cleaved off ADP

How does ATP store in the cells

very small amounts (80-100g under normal, resting conditions
-energy stores also limited to 2-3 second max intensity exercise

How can foods resynthesize ATP

they are catabolized to resynthesize and replenish ATP
-food has potential energy

anaerobic ATP resynthesis

reaction with limited O2 and/or abundant CO2 fueled by:
-Phosphocreatine (PCr)
-Glucose/Glycogen
-Deaminated protein (if necessary)

aerobic resynthesis of ATP

reaction with abundant O2 fueled by:
-pyruvate from glucose/glycogen
-fatty acid
-Deaminated protein (if necessary)

anabolism

Metabolic pathways that construct molecules, requiring energy.
-endergonic

Catabolism

Metabolic pathways that break down molecules, releasing energy.
-exergonic

Phosphocreatine (PCr)/Phosphagen system

-occurs in the cytosol
-hydrolyzing (split) PCr by enzyme creatine kinase (Ck) yields free phosphate (Pi) group
-ADP can then be phosphorylated back to ATP
-creatine then phosphorylated back to PCR using Pi from ATP hydrolysis restarting the cycle
-overall byproducts are Pi AMP, ADP, stimulate other systems

creatine kinase

enzyme that hydrolyzes (splits) PCr

PCr

cells store up to 4-6 times more PCr than ATP
-energy reservoir
-high levels of ADP factor this reaction
-adenylate kinase reaction can assist this fast process

adenylate kinase

enzyme that assists
2 ADP <--> ATP + AMP

glycolysis

substrate-level phosphorylation that generate limited ATP
-yields Net +2 ATP
-require initial -2 ATP investment
-30% efficiency, 5% total atp from complete glucose breakdown
-CRUCIAL FOR MAX INTENSITY LASTING UP TO 90 seconds
-also generates necessary products for oxidative phosphorylation
-electron carriers: +2 NADH
-glucose cleaved to 2 p[yruvate that can convert to lactate

steps of glycolysis

glucose simplifies to glucose 6-phosphate (-1ATP)
-glucose 6-phosphate converts to fructose 6-diphosphate
-fructose-6 diphosphate converts to fructose 1, 6-diphosphate (-1 ATP)
-fructose 1, 6-diphosphate splits into two 3-phosphoglyceraldehydes
-3-phosphoglyceraldehydes individually catabolize by enzyme chain
-result in +4 ATP (+ 2 each), +2 NADH (1 each)
Net yield= +2 ATP, +2 NADH, +2 Pyruvate

hexokinase

enzyme that simplifies glucose to glucose 6-phosphate

phosphorylase

enzyme that converts glycogen to glucose 6-phosphate without ATP

phosphofructokinase (PFK)

enzyme that converts fructose 6-diphosphate to fructose 1, 6-diphosphate

Pyruvate kinase

enzyme that stimulates the production of pyruvate in glycolysis

3 key rate limiting enzymes in glycolysis

hexokinase, phosphofructokinase, pyruvate kinase

GLUT-4 transporters

insulin-regulated glucose transporter
-respond to high levels
-exercise turns them on and glucose enters the cell

glycogen synthase

Enzyme that synthesizes glycogen from glucose.
glycogenesis

Enzyme that synthesizes glycogen from glucose.
glycogenesis

if pyruvate is not used for aerobic glycolysis, lactate dehydrogenase drives the reversible reaction to turn it to lactate

lactate dehydrogenase

converts pyruvate to lactate by uncoupling NAD+ from NADH leaving a free H+ ion
-accumulations of H+ ions drops the pH making muscle environment more acidic
- contributes to muscle soreness

if lactate is not used

it accumulates and so will H+ ions so fatigues sets in

lactate shuttle

-lactate made in fast twitch fibers can be moved to other fast or slow twitch fibers to be converted to pyruvate
- can be oxidized for energy when oxygen becomes available or pace of exercise slows

gluconeogenesis

the liver can convert the pyruvate (from converting lactate) to glucose via the Cori cycle
-glucose then available for use

cori cycle

-begins with the fermentation of pyruvate to lactate in muscle by lactate dehydrogenase
-in the liver, glycolysis is essentially run in reverse
-lactate is converted back to pyruvate
-pyruvate is then converted to glucose
-glucose can then be released in the blood stream and resupply other muscle tissue
-can also resupply liver glycogen which has been depleted by intense exercise

exchangeable lactate pool

in active tissues Cori cycle can contribute to their lactate to mix to replenish glycogen

Electron transport chain (ETC)

the final common pathway where electrons extracted from hydrogen pass to oxygen

-mitochondrial oxygen levels drive the respiratory chain by serving as the final electron acceptor to combine with hydrogen to form water

oxidative phosphorylation

-aerobic metabolism

-occurs within the mitochondria

-passes electrons from the oxidation of a feul source to electron carriers (NADH and FAD2) which will then be passed to oxygen to phosphorylate ADP resynthesizing ATP

2 stages of oxidative phosphorylation

-citric acid cycle

-electron transport chain

citric acid cycle (krebs cycle)

-continues oxidation of carbohydrates

-can also oxidize fatty acids and some amino acids

-primary function is to remove hydrogen ions and associated energy from substrates

-attach H+ to NAD+ and FADH generating electron carriers NADH and FADH2

Acetyl CoA

initiates the Krebs cycle

-formed by from pyruvate (glycolysis)
-carbon is removed from pyruvate and joins with enzyme CoA

pyruvate dehydrogenase

enzyme that converts pyruvate and attaches Coenzyme A to form Acetyl CoA

Citrate synthase

enzyme that joins oxaloacetate with Acetyl-CoA to form citrate (citric acid)

oxaloacetate

starting and ending point for the krebs cycle

Yield of Krebs cycle

2 pyruvate from glycolysis 2 Acetyl-CoA = 2 turns around krebs cycle

Yeilds +6 NADH (3 each), +2 FADH (1 each), +2 ATP (1 each)

Electron Transport Chain

electron (H+) ions which have been passed to carriers NADH and FADH2 can combine with O2 to produce ATP and water

-slow process, high yeild

Oxidation

lose electron

reduction

gain electron

During glycolysis and krebs cycle NAD+ and FADH are…

reduced

-they gained an electron in the form of H+ ions

During ETC NADH and FADH2 are…

oxidized

-they lose electrons

-while oxygen is reduced

cytochrome complexes

complexes that are reduced (gain electron) from NADH and FADH2

• they are on the inner membrane of mitochondria

  • trade elctrons, reducing and oxidizes one another down the bucket chainCO

Coenzyme q and cytochrome C

shuttle electrons between larger complexes

-at respiratory enzyme complex, 2 protons (H+) and ½ O2 join to make water

ATP synthase

the final complex of the ETC

• uses energy from proton gradient to phosphorylate ADP

  • H+ ions flow back across following chemiosmotic gradient

chemiosmotic gradient

path in which H+ ions follow back into mitochondria

COmplex 1

interacts with NADH

COmplex 2

interacts with FADH2

COmplex 4

Where oxygen s the final electron acceptor

Oxidative phosphorylation summary

• electron transport efficiency = 34%

• P/O ratio (phosphagen bonds fromed to oxygen atoms consumed) tells us the efficiency of a feul source’s metabolism

• Each NADH yeilds +2.5 ATP, each FADH2 yields +1.5 ATP

• Overall yield: GLycolysis- 2NADH—→ +6 ATP Krebs - 6NADH 2 FADH2—→ +22 ATP

• Total = 28 ATP + Net 2 ATP GLycolysis + 2 ATP Krebs = +32 ATP

Regulation of Energy metabolizm

-the overall energy state dictates the direction of the metabolic pathways

-rate limiting modulators:

• ATP: still need to spend

• ADP: exerts the greatest effect on rate-limiting enzymes; without ADP we have nothing to rephosphorylate

• cAMP: necessary for fat metabolism

• NAD: necessary for electron carrier without which electron transport is limited

• CA2+: stimulates enzyme in krebs cycle; key for fat metabolism

• pH: can modulate enzymatic activity thereby modulating the rate and efficacy of their reactions

Fat metabolizm

-

fat is mainly stored as

triglycerides

• classified by length of carbon-chain forming FAs

glycerol

• 3 fatty acids

Adipocytes

sites for fat storage and mobilizatoin

Fatty acids (FAs)

what is udes for feuld

-glycerol can be converted to pyruvate via glycolytic actions or repurposed for gluconeogenesis

1 lb of fat =

3500 kcal of energy

lipolysis

-starts fat metabolism

• splittle of tryglycerides into component FA and glycerol

• driven by hormone sensitive lipase (HSL)

• activated intracellularly by cAMP

• stimulated by: sympathetic hormones, glucagon, growth hormone, thyroid stimulating hormone, testosterone

  • FAs are now free fatty acids

hormone sensitive lipase (HSL)

enzyme that drives the splitting of triglycerides into component Fatty acids and glycerol

Free fatty acids

transported in blood plasma by albumin

• can enter mitochondria for metabolism

  • can be re-esterified back to TG

Beta-oxidation

Catabolism of fatty acids

• aerobic process

• transforms FA into acetyl CoA in mitochondria

• Transported by transferring acetyl group to carnitine

• 2 C groups are cleaved off from fatty acetyl CoA molecule

• these acetyl groups enter the krebs cycle

• high fat diets like keto increase reliance on this

Is Fat metabolism effective

-Fat metabolism yields more nergy but is slower than carb metabolism

-P/O ratio is lower than carbs

-carb metabolism maintains ozidatoin rates

-glycolytic pyruvate keeps oxaloacetate in sufficient supply to sustain beta-oxidation

-Carb depletion more severly impacts exercise performance

• necessary fro faster anaerobic activities

  • hinders fat metabolism for enduranc

Deaminated protein

-nitrogen removed from the amino acid in the liver and muscles

• yields intermediates for gluconeogenesis from glucogenic AA

• yield intermediates for acetyl CoA or acetoacetate TG formation from ketogenic AA

-remaining carbon skeleton enters metabolic pathways to produce ATp

Transaminated protein

amine group is transferred

• new AA formed

  • replaced intermediates for krebs cycle

the Metabolic Mill

-citric acid cycle is Vital link between macronutrient (carbs, lipids, proteins) energy and chemical energy in ATP

• serves as a metabolic hub to shuttle intermediates that cross the mitochondrial membrane into the cell cytosol

SUmmary

-out body is constantly seeking to replenish its limited ATP stores

-PCr system yields a fast but very limited solution

-glycolysis is more efficient (Especially if aerobic)

-oxidative phosphorylation or ETC yields the highest return of ATP

-Fats and proteins can be used too:

• feed into aerobic glycolytic processes

• fat can yield huge amounts of energy, but doesn’t have the same overall efficiency as carbs (also depends on aerobic glycolysis

• proteins are a last resort and fill in gaps or amplify fat and carb metabolism

Our body only has enough ATP in storage to sustain max intensity exercise for how long

3-4 seconds

• with PCr = 10 seconds

Which macronutrient yields the greates amount of energy

fats

FADH2 transfers electron to which complex of ETC

complex 2

What is chemiosmosis

ATP synthase (COmplex 5)

Total energy transfer from fat catabolism

1 molecule glycerol = 10 ATP yield per molecule neutral fat

3 molecules carbon fatty acid = 441 ATP yield per molecule neutral fat