Mod 2: Oxidative And Non-oxidative Metabolism During Exercise

Question 1

What is the location and fuel storage forms of the major energy systems? Phosphagen, glycolytic, oxidative

Answer 1

Phosphagen: cytosol of mitos, no O2, fuel stored as phosphocreatine (PCr) 1. Rxn to produce atp

Glycolytic: cytosol of mitos, no O2, fuel stored as glucose and glycogen. 10 rxns to produce atp

Oxidative: in mitos, needs O2, fuel stored as glucose, glycogen, fatty acids, triglycerides, and amino acids. >10 rxns

Question 2

Explain the rate vs duration trade-off of atp supply

Answer 2

As PCr decreases atp slightly increases then stays high then gets low with the decrease of PCr

Question 3

Explain the PCr energy system chemical reaction

Answer 3

The enzyme creatine kinase(highly regulated by substrate concentration, ex. PCr and ADP available signals creatine kinase activities to increase ) facilitates the reaction: PCr+ ADP <—> ATP + Cr .

ATP: 1 adenosine, 3P
PCr: 1 creatine, 1 P.

PCr splits into 1 creatine and 1P, the P combines with ADP to form ATP with the help of free energy and creatine kinase.

PCr combines with ADP which allows phosphate in creatine to become 3rd phosphate group on ATP

Question 4

What are the strengths and limitations of the PCr energy system?

Answer 4

Strengths: only one quick reaction, an instantaneous process to produce atp

Weaknesses: substrate quickly depleted, only 1 unit of ATP formed per unit substrate(PCr)

Supplementing in creatine: weight gain (water weight)

Question 5

When do we rely heavily on phosphagen stores?

Answer 5

1. Intense exercise (100m sprint)
2. Rest to work transition (standing up from chair)
3. Workload transitions in exercise( riding bike, have to go up hill)

Question 6

Describe the key enzymes, substrates, and products of non-oxidative glycolysis

Answer 6

Hexokinase: phosphorylates glucose to G6-P so it can’t leave the cell (have to store it or use it)

GLUT 4 transporter: get glucose into skm

Glycogen phosphorylase: glycogen broken down to —> G1-P (breakdown of glycogen molecule so we can use it )

Phosphofructokinase(PFK): (rate limiting enzyme) regulated by ADP and ATP conc: increase in ADP conc = enhance PKF activity and speed up glycolysis because we need more ATP, lots of ATP available =inhibits PKF

-energy transfer : use atp to make an ADP (net loss at beginning)glucose —> G6p

ATP NET GAIN:

Glucose: 2
Glycogen : 3

Reduction of NAD to NADH + H

Question 7

What is the ATP yield from non-oxidative use of glucose and glycogen

Answer 7

Glucose: 2 ATP
Glycogen: 3 ATP

Question 8

What is the role of lactate formation in non-oxidative glycolysis

Answer 8

When O2 is low, pyruvate from glycolysis can’t turn into acetyl coA —> krebs—> ETC —> produce ATP so it ferments and turns into lactate which is a reduction process.

-facilitated by enzyme lactate dehydrogenase
Pyruvate —-> lactate
-in process NADH oxidized —> NAD+, which is supplied to glycolysis to continue making ATP

Lactic acid —> H + lactate

-immidetely dissociates ph goes low to 6.5 which is problematic in terms of enzyme activity

Decreased muscle pH —> metabolic inhibition —> decreased enzyme activity

Decreased muscle pH —> contractile inhibition —> decreased cross bridge cycling

-H ion accumulation is the problem that lowers pH

• lactate continues to cori cycle to keep up glycolysis

Question 9

what are the strengths and limitations of the glycolytic energy system?

Answer 9

Strength: don’t run out of glycogen

Limitation: substrate availability, enzyme activity, lactate accumulation

Question 10

What is non-oxidative glycolysis?

Answer 10

When we run out of PCr stores we partially breakdown glucose and glycogen without oxygen.

-quick process but limited by metabolic by-products(don’t run out glucose, gets inhibited by accumulation of byproduct)

-2-3 ATPs formed/unit of substrate

Question 11

Glycolysis vs glycogenolysis

Answer 11

Glycolysis: breakdown of 1 glucose to form 2 Pyruvate

Glycogenolysis: breakdown of 1 glucose (6C) from glycogen to form glucose-1-phosphate

6C glucose —> glucose-6-phosphate(g-6-p) —> 2xpyruvate (3C)

Glycogen —> glucose-1-phosphate —> g-6-p

Question 12

What happens to pyruvate in non oxidative glycolysis ?

Answer 12

In cytosol:
If Oxygen is available turns into —-> acetyl coA, facilitated thru enzyme pyruvate dehydrogenase (in mito). NAD+ —> NADH + H

No oxygen: turns into lactate (lactic acid) thru enzyme lactate dehyogenase . NADH + H—> NAD +

Question 13

When do we rely heavily on non oxidative glycolysis

Answer 13

Intense exercise
Rest to work transtition
Workload transtition

Question 14

Explain the essential steps involved in oxidative metabolism

Answer 14

3 essential steps:

1. Formation of acetyl coA (from CHO,fat,a.a)
2. Oxidation of acetyl coA (kerbs cycle)
   -coenzymes are reduced
3. Formation of ATP (electron transport chain)
   -coenzymes are oxidized

Question 15

Identify the location in the mitochondria where relevant aspects of oxidative metabolism occur

Question 16

What is oxidative metabolism

Answer 16

The complete breakdown of carbs, fats, amino acids, to CO2 and H2O
-requires oxygen but provides sustained energy
-occur in MITO
->30 atps formed per unit of substrate

Question 17

How is acetyl CoA formed from carbohydrates?
-formula
-enzyme
-location

Answer 17

Pyruvate + NAD –> acetyl coA + CO2 + NADH
- facilitated by enzyme pyruvate dehydrogenase (PDH)
-ability to use carb aerobically measured by PDH

-NAD reduced to NADH

-location: inner mitochondrial membrane

Question 18

List the key “outputs” derived from acetyl coA oxidation

Answer 18

1 atp
1 fadh2
3 nadh

Question 19

What is the role of co-enzymes in oxidative metabolism?

Answer 19

Coenzymes facilitate redox reactions by helping molecules or atoms lose electrons during oxidation and gain electrons during reduction

• like citrate synthase, cytochrome oxidase, pyruvate dehydrogenase

Question 20

Describe the essential steps of the electron transport chain

-enzymes

Answer 20

-series of ox-red reactions
-electrons passed from NADH and FADH2(BOTH OXIDIZED) to O2 which forms H2O via reduction

-MORE ENERGY FROM nadh (2.5 atp) than fadh (1.5 atp)

• NADH –> NAD+ (ox)
  -FADH2–> FAD(ox)
  -O2–> H2O (red)

-enzymes: cytochrome oxidase
ATP synthase: ADP + Pi –> ATP

Question 21

What’s the ATP yield from aerobic (with oxygen) use of carbohydrate(from 1 glycogen)

Answer 21

33 atp

Question 21

what is the enzyme that facilitates the reaction :
acetyl coA (2C) + oxaloacetate(4C) —> citrate (6C)
-in th

Answer 21

CITRATE SYNTHASE
-more citrate synthase in muscle =more mitos
ex. athletes have more than sedentary ppl

Question 22

What is the basic structure of a triglyceride?

-2 main TG sources?

Answer 22

3 fatty acid chain attached to a glycerol backbone

-main sources of TG:
1. Adipose tissue
2.skeletal muscle

Question 23

Explain the steps involved in triglyceride catabolism to ATP

Answer 23

1. Mobilization :

-TG breakdown : get fatty acid off of glycerol backbone (occur in adipose tissue) —> lipolysis

2. Transport: fatty acids circulate in blood and get to skm (carried in blood via albumin (protein))
3. Uptake : (by skm) fatty acid enters muscle cytosol
4. Activation: fatty acid prepared for breakdown (requires a bit of atp) formation of fatty acyl CoA
5. Uptake: fatty acid enters MITOS
6. Beta oxidation: FA broken down IN MITOS (makes acetyl coA and NADH and Fadh, unique to fats)
7. Mito oxidation: TCA cycle/ ETC activity)

Question 24

Why is carnitine in fat oxidation important?

Answer 24

When fatty acyl - CoA is in the cytosol after coming into blood via FA transporter (original form was a, turned into fatty acyl co A), carnitine palmitoyl transferase(CPT)(enzyme) acts as an escort to get it into mito matrix so it can be used for aerobic energy (regulates ability to oxidize FAs) -use FA stores during exercise when carb stores are low -popular weight loss supplement because it oxidizes fat to be used for energy ( doesn’t work bc it doesn’t get into skm )

Question 25

What are the key “outputs” of beta oxidation?

Answer 25

- by products : 1 FADH, 1 NADH, —-> go directly to ETC 1 acetyl coA —> goes to krebs TCA cycle (Fatty acyl coA gets 2C shorter to generate the acetyl coA) - enzyme: beta HAD -end with 14C fatty acyl coA from 16(lost 2C), and goes thru cycle again till it goes down to 2 C which immedtely forma acetyl coA

Question 26

What’s the atp yield from oxidation of a fatty acid?

Answer 26

Start with 16 C fatty acyl coA (Total # C/2)-1 = how many cycles of beta oxidation occur 16/2 -1=7 turns For palmitate (16-C fatty acid) Each turn of Beta oxidation: - 1 FADH (1.5 atp) - 1 NADH (2.5 atp) - 1 acetyl coA (3 NADH, 1 FADH, 1 ATP = 10 atp) TOTAL ATP per cycle of beta oxidation :14 ATP x 7 turns = 98 ATP per palimiate molecule Remaining 2C unit forms 1 acetyl coA = +10 atp Minus energy for “activation” of FA : -1 atp TOTAL YIELD: 106 ATP per palmitate molecule

Question 27

Explain the first step of fatty acid catabolism: fatty acid mobilization

Answer 27

- occurs in adipose tissue and skm if tgs are stored there -break down tgs into 3 FAs and 1 glycerol (by enzyme HSL) hormone sensitive lipase -glycerol goes to liver—> convert to glucose - FAs go to muscle to be catabolized for energy -enzymes that regulate lypolysis: HORMONE-SENSITIVE LIPASE(HSL)(in adipose and muscle)—-> breaks down TG into FA and glycerol

Question 28

Explain fatty acid transport, uptake, and activation

Answer 28

- FA from blood enters cytosol of cell via FA transporter and turns into fatty acyl-CoA by adding a CoA to it (FA now activated and can be recognized by mitos now), uses 2 atp - fatty acyl-coA enters mito matrix through enzyme carnitine palmitoyl transferase (CPT) that allows the uptake so it can be used for aerobic energy provision -CPT regulates ability to oxidize fat

Question 29

Explain beta oxidation (step 6)

Answer 29

Only occurs for fatty acids in mitos once fatty acyl co A gets in thru CPT transporter enzyme - by products : 1 FADH, 1 NADH, 1 acetyl coA (Fatty acyl coA gets 2C shorter to generate the acetyl coA) - enzyme: beta HAD

Question 30

Is carbs (glucose) or fat (palmitate) a better fuel source?

Answer 30

Glucose: 4 kcal/g, capacity: 2500 kcal, atp generated/1 carbon: 32 atp/ 6 carbon= 5.3 ratio atp/O2 =5.3 Palmitate: 9kcal/g, capacity: unlimited, atp generated / 1 carbon: 106/16=6.6 ratio, atp generated/unit of O2 =4.6 Fat more Efficient in all except atp/O2: (carbs are 10% more O2 efficient -at rest fat is preferred, in exercise arbs are preferred because oxygen is limiting , permits exercise at a higher pace

Question 31

When do we rely heavily on oxidative metabolism?

Answer 31

-rest -steady state exercise Any form of exercise lasting more than 2 mins

Question 32

Describe amino acid catabolism

Answer 32

1. Removal of amino group: -major site: liver -minor site: skm (Branched chain amino acids) 2. Oxidation of remaining “carbon skeleton” (“oxo acid”) -eventually form pyruvate or acetyl coA Major AAs in exercise metabolism : - BCAA ( leucine, isoleucine, valine) -alkaline, glutamine -remove nitrogen group to use amino acid as energy -alkaline and glutamine take nitrogen to liver to convert to urea

Question 33

Describe the process of gluconeogenesis

Answer 33

Recycling of metabolic by-products The formation of new glucose from metabolic intermediates -metabolic byproduct of anaerobic glycolysis: lactate —>helps regenerate NAd for glycolysis (in liver) -amino acids : alkaline and glutamine take nitrogen to liver -break down TG thru lipolysis : glycerol and 3 FAs - glycerol —> goes to liver,, reforms glucose, leaves liver TLDR: glucose, CHO: lactate, AA: alaline , go to liver from skm Glycerol goes to liver from adipose tissue

Question 34

Key signals for regulation of energy provision

Answer 34

ATP/ADP ratio Calcium levels Hormones -activate enzymes

Question 35

What are some branch chain amino acids: liv

Answer 35

Valine, isoleucine, leucine NOT BCAA: glutamine

Question 36

Can we break down amino acids to form acetyl coA?

Answer 36

Yes

Question 37

T or F Metabolic byproducts derived from the catabolism of carb, proteins, and fat can alll be used for gluconeogenesis

Answer 37

TRUE

Question 38

how many ATP does 1 unit of glucose produce? glycogen?

Answer 38

glucose: 32 ATP glycogen: 33 ATP

Question 39

what are the 3 outputs of acetyl coA oxidation?

Answer 39

1 ATP 1 FADH2 3 NADH

Question 40

what are the 3 essential steps in oxidative metabolism? FOF

Answer 40

1. formation of acetyl coA 2. oxidation of acetyl coA (in krebs) COENZYMES REDUCED 3. formation of ATP (in e.t.c) COENZYMES OXIDIZED

Question 41

what are the 3 outputs of beta oxidation? enzyme:

Answer 41

1 NADH 1 FADH2 1 acetyl coA enzyme: beta HAD