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Y1S2 Biochemistry > Muscle function, energy supply > Flashcards

Muscle function, energy supply Flashcards

1
Q

What is the main source of energy for the musculoskeletal system and general info about energy for the muscles?

A

Glucose

1) Each cell has 1 billion ATP molecules that last for less than one minute

2) 60-70% of the energy in the human body is degraded to heat, the remainder is for the mechanical work and cellular activities

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1
Q

What is the main energy source for the cardiac muscle?

A

Fatty acids

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2
Q

What is the main source of energy?

A

Carbohydrates and the most important form of energy is ATP

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3
Q

Can we store ATP?

A

No, because ATP are regulators as they will affect the activation and inhibition of the pathway

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3
Q

How does our body avoid ATP accumulation?

A
  • ATP has 3 phosphates and the 3rd phosphate is the phosphate that has the highest amount of energy so, in this case, the enzyme creatine phosphate will take that phosphate and add it to creatine-forming creatine phosphate (as a storage form) and ADP
  • Once we need that ATP we convert the Creatine phosphate back to creatine adding the phosphate to ADP
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4
Q

Where is creatine phosphate mostly found?

A

in the muscles

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5
Q

Where does gluconeogenesis occur in the body?

A

In the liver

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6
Q

What are the different energy sources available for the muscles?

A

1) From glucose (aerobic & anaerobic)

2) From TCA cycle

3) From muscle glycogen

4) From gluconeogenesis, protein & fat

5) From creatine phosphate

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7
Q

What is the importance of glucose?

A

1) Yields a great amount of energy upon oxidation

2) It can be efficiently stored in a polymeric form

3) Many organisms and tissues can meet their energy needs on glucose only

4) Some tissues like the brain use only glucose for their energy needs

5) It is a precursor to synthesize the skeleton of many different structures (like the non-essential amino acids)

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8
Q

What is the importance of glycolysis?

A
  • Sequence of enzyme-catalyzed reactions where glucose is converted into pyruvate, which can be further oxidized aerobically in addition to that it can be used as a precursor in biosynthesis
  • Glycolysis is divided into 5 investment stages where 2 ATPs are used and 5 payoff stages where 4 ATPs and 2NADH are produced
  • It requires no oxygen
  • 10-step reaction that occurs in the cytoplasm
  • The end products are two pyruvates that depend on the availability of oxygen in the cell, if O2 was available then we would get the 6CO2 if not there would be a different fate
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9
Q

How can we gain energy from glycolysis?

A

1) Substrate level phosphorylation (“Cash” ATP): usually uses kinases, in a reaction that converts a high-energy molecule to a low-energy one via transferring a phosphoryl group

2) Oxidative phosphorylation, Electron carriers that can be converted into ATP (“Coupons” NADH/FADH2): they are electron carriers that are converted into energy via the ETC using oxidative phosphorylation, this is the main source of energy production

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10
Q

What are the regulatory steps in glycolysis?

A

1) Reaction number 1: Converting glucose into glucose-6-phosphate, using ATP converting it into ADP, via the enzyme hexokinase

2) Reaction number 3: Converting Fructose-6-phosphate into fructose-1,6-bisphosphate via the enzyme phospho-fructokinase-1, using ATP converting it into ADP

3) Reaction number 10: converting phosphoenolpyruvate into two pyruvates, via the enzyme pyruvate kinase, producing 2 ATP’s from 2 ADPs

  • all of their enzymes are kinases
  • The only kinase that reacts reversibly in glycolysis is phosphoglycerate kinase
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11
Q

Which reactions in glycolysis produce energy?

A

1) Reaction number 6 (oxidation-reduction rxn): converting glyceraldehyde-3-phosphate into 1,3-bisphosphoglycerate via the enzyme glyceraldehyde-3-phosphate dehydrogenase using 2 phosphates and 2NAD producing 2 NADH + 2H

2) Reaction 7: converting 1,3-bisphosphoglycertae into 3-phosphoglycerate via the enzyme phosphoglycerate kinase (the only reversible kinase) converting 2ADP into 2ATP

3) Reaction number 10: converting phosphoenolpyruvate into two pyruvates, via the enzyme pyruvate kinase, producing 2 ATP’s from 2 ADPs

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12
Q

What is the commitment step in glycolysis?

A

Reaction number 3 converting fructose-1-phosphate into fructose-1,6-bisphosphate using phospho-fructokinase-1 converting an ATP into ADP

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13
Q

What is the importance of the first reaction in glycolysis?

A

1) It adds a phosphate onto glucose making it unable to leave the cell

2) decreases the concentration of glucose favoring its entry into the cell

3) this reaction also G6P will not always continue towards glycolysis but it will be used in different pathways depending on the cell’s need

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13
Q

Summarize the energy production in glycolysis

A

1) Things we used: 2ATP & 2NAD+

2) Things we made: 2 pyruvates, 4 ATP, 2 NADH (must be reoxidized for glycolysis to continue)

  • Glycolysis is heavily regulated (ensures proper use of nutrients, and the production of ATP only when needed)
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14
Q

How is glycolysis inhibited and activated?

A
  • Glycolysis requires glucose and NAD+ to start

1) Inhibited by high levels of ATP

2) Activated by high levels of AMP

15
Q

What is the fate of pyruvate?

A
  • Depends on the availability of oxygen

1) If O2 is available, Pyruvate is oxidized to Acetyl-CoA which enters the Krebs cycle

2) If O2 is not available pyruvate is reduced to lactic acid via the enzyme lactate dehydrogenase (this is the final product in anaerobic glycolysis in eukaryotic cells, or ethanol in different organisms) and this solves the NAD+ problem as more NADH is produced and there is little to no NAD+ available

  • The body produces lactate relying on the fact that O2 will eventually enter the body (the body will utilize the lactate by transforming it into pyruvate and then into glucose) this occurs in the liver as the lactate travels to it via the blood “Cori Cycle”
16
Q

What happens in our body when we exercise vigorously?

A

1) NADH production exceeds the oxidative capacity of the respiratory chain, increasing the NADH/NAD+ ratio and favoring the reduction of pyruvate to lactate

2) Lactate will then accumulate in the muscles causing a drop in the pH, resulting in muscle cramps

3) Most of this lactate will then diffuse into the bloodstream where it can be used by the liver to make glucose

17
Q

What is meant by lactic acidosis?

A

Elevated concentrations of lactate in the plasma, occur when there is a collapse in the circulatory system, like Myocardial infarction, pulmonary embolism, and uncontrolled hemorrhage

18
Q

Describe the Cori cycle

A

It is the reverse of glycolysis as the lactate reaches the liver it is converted back to glucose utilizing 6 ATP’s for the muscle to use that glucose and produce 2 ATP’s (futile cycle)

19
Q

What happens if we do not have enough glucose for glycolysis?

A

1) Cori cycle

2) Glycogen breakdown (glycogenolysis)

20
Q

How do we produce energy from the breakdown of glycogen?

A
  • Glycogen is the storage form of glucose
  • Glycogen is made up of two bonds (a-1,4) between the glucose molecules and (a-1,6) the branching bond
  • Glycogen phosphate (contains pyridoxal phosphate PLP as a prosthetic group “vitamin B6 derivative”) leaving us with some (a1,6 branches) and glucose-1-phosphate, which is converted to glucose-6-phosphate by phosphoglucomutase
  • a1,6 bond will be broken down by debranching enzyme which has two activities (transferase (which moves some of the glucose in the branch to the main chain “only 3 glucose residues” from a 4-limit branch) and 1,6 glucosidase)
21
Q

What happens to the pyruvate when there is oxygen?

A

Cellular respiration takes place, pyruvate is converted to Acetyl-CoA (an important step that is not part of glycolysis nor the Krebs cycle)

22
Q

What is cellular respiration?

A
  • Process in which O2 is consumed and CO2 is produced
  • Provides more energy “ATP” from glucose than glycolysis
  • Captures energy stored in lipids and amino acids
  • Used by animals, plants and many microorganisms
  • It occurs in three major stages (acetyl-CoA production by PDH “Acetyl-CoA can also be obtained from amino acids and fat metabolism”, Acetyl-CoA oxidation, electron-transfer, and oxidative phosphorylation)
23
Q

What are the important steps in Krebs “TCA, citric acid cycle” cycle?

A
  • Pyruvate must enter the mitochondria for it to go into the TCA cycle, once in the matrix it is converted to acetyl CoA by pyruvate dehydrogenase complex (multi-enzyme complex), the end products are 2 acetyl-CoA, 2CO2, and 2NADH

1) Reaction number 1: converting acetyl-CoA into citrate via citrate synthase in a condensation reaction it is a regulatory step

2) Reaction number 4: converting isocitrate to a-ketoglutarate via isocitrate dehydrogenase enzyme this is a regulatory step and a step that produces NADH

3) Reaction number 5: converting a-ketoglutarate into succinyl-CoA via a-ketoglutarate dehydrogenase complex producing NADH and it is a regulatory step

4) Reaction number 6: converting succinyl-CoA into Succinate producing GTP

5) Reaction number 7: converting succinate into fumarate producing FADH2

6) Reaction number 9: producing oxaloacetate and NADH from malate via malate dehydrogenase

  • Each cycle of the TCA cycle produces: 3NADH, 1FADH2 & 1ATP for each acetyl-CoA
24
Q

Describe the electron transport chain

A
  • All of the NADH, and FADH2 formed during glycolysis, b-oxidation, and the TCA cycle, give up their electrons to reduce O2 into H2O
  • They occur via a series of protein electron carriers and the final acceptor is O2
  • It takes place in the inner mitochondrial membrane where all electron carriers are present
  • ETC facilitates a controlled release of free energy that was stored in reduced cofactors during catabolism
25
Q

What are the two main steps in the electron transfer chain?

A
  • it is strictly aerobic
  • ETC inhibitors (meds) will kill the cell as there is no energy (in case they inhibit complex 1, 3 & 4) but not 2 it will just reduce the energy

1) Electron Transfer

2) Oxidation phosphorylation

26
Q

What are the steps in the electron transfer phase of the ETC?

A
  • It is found in the inner membrane of the mitochondria
  • Uses oxidative phosphorylation to convert NADH and FADH2 into ATP
  • We have complexes 1, 2, 3, and 4 for the electron transfer
  • Complex 1 is a proton pump, and it is the entry point of NADH
  • Complex 2 is not a proton pump, and it is the entry point of FADH2
  • Complexes 3 & 4 are electron pumps and accepts electrons from complex 1 & 2
  • Electron carriers produced from glycolysis and citric acid cycle (NADH & FADH2) will approach complexes 1 & 2 passing their electrons until they reach the oxygen within the cell
  • As the electrons pass through the complexes, protons like H+ are pumped from the matrix into the intermembrane space creating a high electrochemical concentration of protons
  • Oxygen is the final electron acceptor
  • Then ATP Synthase will allow these protons to move within their concentration gradient from the inner membrane space through its complex to the matrix and ATP will be produced from ADP and Pi
27
Q

What is the difference between uncouplers and ETC inhibitors Drugs?

A

Uncouplers are drugs that inhibit ATP synthase, while ETC inhibitors are drugs that inhibit the ETC but both of them lead to no energy

28
Q

How many ATP’s are produced by NADH?

A

3

  • Each pump 1, 3, & 4 pumps 1 H+, and each H+ converts 1 ADP into 1 ATP
29
Q

How many ATP’s are produced by FADH2?

A

2

  • As complex 2 is not a pump, H+ will only be pumped by complex 3 & 4 yielding 2 ATP molecules
30
Q

What is the net ATP produced from the complete glycolysis of glucose?

A

36-38

Why is it 36-38

as the NADH produced in step 6 in glycolysis is outside the mitochondrial matrix and transferring it into the mitochondrial matrix has two shuttles one of them will convert it to FADH2 yielding one less ATP for each NADH (glycerol-3-phosphate shuttle & aspartate malate shuttle)

31
Q

Describe the general steps in the net ATP produced

A

1) Glycolysis
- 2 ATP
- 2 NADH

2) PDH (pyruvate dehydrogenase) Complex
- 2 NADH

3) TCA cycle
- 2 GTP/ATP
- 6 NADH
- 2 FADH2

4 ATP + (10 * 3 =) 30 ATP + (2 *2=) 4 ATP = 38 ATP’s

32
Q

What is gluconeogenesis?

A
  • Synthesis of glucose from a non-carbohydrate source
  • Requires both the mitochondria and the liver
  • Its substrates are (glycerol, lactate, & amino acids)
  • Opposite to glycolysis
33
Q

What are the main reactions in gluconeogenesis?

A
  • It is the reactions that are opposite to the 3 regulatory steps in glycolysis (rxn 1, 3, & 10)
  • We must use 6 ATP’s to transform pyruvate into glucose
  • Lactate must be converted to pyruvate before we start gluconeogenesis

1) Reaction number 1 (pyruvate back to PEP): Pyruvate will be converted to oxaloacetate via the enzyme pyruvate carboxylase utilizing one ATP (converting it to ADP + Pi) and one CO2

2) Reaction number 2 (pyruvate back to PEP): we will convert oxaloacetate to phosphoenol pyruvate via the enzyme PEP carboxykinase releasing one CO2 utilizing one GTP converting it to GDP

3) Reaction 10 (number 3in glycolysis): converting fructose-1,6-bisphosphate to fructose-6-phosphate via fructose-1,6-bisphosphatase utilizing one ATP

4) Reaction number 11 (number one in glycolysis): Converting glucose-6-phosphate into glucose via the enzyme glucose-6-phosphatase utilizing one ATP

34
Q

What are the important stuff regarding gluconeogenesis?

A
  • It occurs in the cytoplasm and mitochondria
  • reverse 11 steps
  • and the three important enzymes
  • Glucose-6-phosphatase is only present in the endoplasmic reticulum of the liver which is why gluconeogenesis occurs in the liver
35
Q

Describe the ATP coming from creatine

A
  • It is the first source of energy for the muscles that lasts for a few minutes
  • ATP is not stored as it is an important regulator for many pathways

1) Creatine phosphate is found in the muscles and it is a high-energy compound that provides a small but rapidly mobilized reserve of high-energy phosphates which can be reversibly transferred to adenosine triphosphate to maintain the intracellular level of ATP during the first few minutes of muscle contraction

  • It is a reversible reaction where ATP transfers its third phosphate to creatine via creatine kinase producing ADP and creatine phosphate, and this is the way we reserve ATP
36
Q

Describe the energy from protein sources

A
  • Provides less than 5-10% of total energy
  • Amino acids are converted to glucose by gluconeogenesis
  • Various intermediates enter the TCA cycle
  • The alanine-glucose cycle is found in the muscle
37
Q

Describe the energy stores from fats

A
  • Muscles & liver glycogen stores 1,200-200 kcal
  • Muscle & fat cells store 75,000 kcal
  • Triglycerides are the major energy source
  • TG is broken to glycerol and FFA (lipolysis by lipases)
  • fat oxidation requires more O2 than CHO oxidation
38
Q

How much energy is yielded from proteins, carbohydrates, and lipids?

A

Protein and carbohydrate = 4 kcal/g

Lipids = 9 kcal/g

39
Q

What is the cofactor that is required by pyruvate carboxylase?

A

Biotin

Y1S2 Biochemistry (4 decks)

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