Metabolic pathways and ATP I Flashcards
What are the three principle forms of food molecules used by the cells?
Polysaccharides –> simple sugars
Proteins –> amino acids
Fats –> glycerol and fatty acids
Describe the 3 main stages of cellular metabolism
- Glycolysis - oxidation of glucose within the cytosol of cells, generating ATP and NADH. Anaerobic process.
- TCA cycle/citric acid cycle - further oxidation of small molecules generated by glycolysis within the mitochondria of cells, generating ATP, NADH, FADH2 and waste products
- Oxidative Phosphorylation - generation of ATP within the mitochondria by the reduction of oxygen to water
List the 6 types of reactions that define metabolism
- Oxidation-reduction - electron transfer
- Ligation requiring ATP cleavage - formation of covalent bonds
- Isomerisation - rearrangement of atoms to form isomers
- Group transfer - transfer of a functional group from one molecule to another
- Hydrolytic - cleavage of bonds by the addition of water
- Addition or removal of functional groups - Addition of functional groups to double bonds or their removal to form double bonds
Describe the stages of glycolysis (first half)
- Glucose –> glucose-6-phosphate (by hexokinase, using hydrolysis of ATP to ADP)
- All kinases catalyse the transfer of a phosphate group from a donor such as ATP, onto a substrate
- An irreversible reaction and traps glucose inside the cell due to neg. charge - Glucose-6-phosphate –> fructose-6-phosphate (by phosphoglucose isomerase)
- The logic behind this reaction is that fructose can be split into equal halves when subsequently cleaved - Fructose-6-phosphate –> fructose-1,6-bisphosphate (by phosphofructokinase using ATP)
- Here a highly symmetrical, high energy compound is generated.
- Regulation of phosphofructokinase exquisitely controls the entry of sugars into the glycolysis pathway. - Fructose-1,6-bisphosphate –> glyceraldehyde 3-phosphate + dihydroxyacetone phosphate (by aldolase)
- An opening of the fructose ring to generate two high energy compounds, one of which, (dihydroxyacetone phosphate) subsequently undergoes isomerisation. - Dihydroxyacetone phosphate –> glyceraldehyde 3-phosphate (by triose phosphate isomerase (TPI))
Describe the stages of glycolysis (second half)
- Glyceraldehyde 3-phosphate –> 1,3-bisphosphoglycerate (by glyceraldehyde
3-phosphate dehydrogenase)
- NAD+ + Pi = NADH
- NADH is generated here which can be later used to generate yet more ATP within the mitochondria in a process known as oxidative phosphorylation - 1,3-bisphosphoglycerate –> 3-phosphoglycerate (by phosphoglycerate kinase, produces ATP)
- A phosphate group is transferred to an ADP molecule to give ATP. - 3-Phosphoglycerate –> 2-phosphoglycerate (by phosphoglycerate mutase)
- Shuffling of the phosphate group from the 3 to the 2 position. - 2-phosphoglycerate –> phosphoenolpyruvate + H2O (by enolase dehydration)
- Phosphoenolpyruvate –> pyruvate (using pyruvate kinase and producing ATP)
Transfer of the high energy phosphate group to ADP, generating one ATP molecule in the process.
Define substrate level phosphorylation and how this differs to other ways of producing ATP.
The formation of ATP in glycolysis is called substrate-level phosphorylation because ATP was produced by the direct transfer of a high-energy phosphate group from an intermediate source in the biochemical pathway to ADP
Contrasted to oxidative phosphorylation where ATP is produced using energy derived from the transfer of electrons
What happens to pyruvate in alcoholic fermentation
It can be turned into ethanol (anaerobic condition in yeasts)
- Pyruvate –> acetaldehyde (using pyruvate decarboxylase and producing CO2
- Acetaldehyde –> ethanol (using alcohol dehydrogenase and NADH + H+ = NAD+)
what happens to pyruvate in generation of lactate?
Can be turned into lactate (characteristic in anaerobic organisms and mammals during intensive exercise)
Pyruvate —> lactate (using lactate dehydrogenase and NADH + H+ = NAD+)
What is the importance of alcoholic fermentation and generation of lactate?
Regeneration of NAD+ is essential for glycolysis to continue, in conditions of oxygen deprivation.
Alcoholic fermentation and the generation of lactate serve the purpose of regenerating NAD+.
needed for the dehydrogenation of glyceraldehyde 3-phosphate to 1,3 bisphosphoglycerate, which is the first step in generating ATP for the body.
NAD+ + Pi—–> NADH
describe the process of pyruvate to acetyl coA
- Pyruvate + HS-CoA –> acetyl CoA + CO2
(using pyruvate dehydrogenase complex and NAD+ –> NADH)
Occurs in the mitochondria
Acetyl CoA formed is able to enter into the citric acid cycle and ultimately produce ATP by process of oxidative phosphorylation
Define the function of creatinine phosphate
- Creatine phosphate is a large reservoir of phosphate which can be used to phosphorylate ADP to ATP.
- Creatine kinase catalyses the reaction of:
creatine phosphate –> creatine + ATP
enzyme: creatine kinase
Function of thiamine pyrophosphate (TPP)
- derivative of vitamin B1
- Thiamine pyrophosphate (TPP) readily loses a proton and the resulting carbanion attacks that of pyruvate to make hydroxyethyl-TPP
- A deficiency of thiamine (vitamin B1) is a cause of Beri-Beri symptoms include:
- damage to the peripheral nervous system,
- weakness of the muscles and
- decreased cardiac output. The brain is particularly vulnerable too, as it relies heavily on glucose metabolism
Function of lipoamide
- Functional group undergoes oxidation and reduction.
- long arm allows dithiol group to swing from one active site to another.
- Arsenite and mercury have high affinity for neighbouring sulphydryl groups and will readily inhibit pyruvate dehydrogenase.
Function of FAD(Flavine Adenine Dinucleotide )
FAD accepts and donates two electrons with two protons:
FAD + 2e- + 2H+ —> FADH2
What charge does glucose-6-phosphate have and what is the consequence of this
Negative
Means it traps the glucose inside the cells.
What is the structure of fructose-1,6-bisphosphate
Highly symmetrical and a high energy compound is generated.
Which enzyme can be controlled to control the entry of sugars into the glycolysis pathway.
Phosphofructokinase.
How quickly do sufferers of Triose phophate isomerase die?
Within the first 6 years
What is substrate level phosphorylation?
the production of ATP by the direct transfer of a high-energy phosphate group from an intermediate substrate in a biochemical pathway to ADP, such as occurs in glycolysis.
What are the net products of glycolysis?
2 ATP + 1 NADH
Which steps of glycolysis use and produce ATP?
USE
Glucose –> G6P (-ATP) Fructose-6-phosphate –> Fructose-1,6-bisphosphate (-ATP)
MAKE
1,3-bisphosphoglycerate –> 3-phosphoglycerate (+ATP) Phosphoenolpyruvate –>Pyruvate (+ATP)
What are the three fates of pyruvate?
Alcoholic fermentation: happens in yeast under anaerobic conditions
Generation of lactate: happen in mammals
Generation of Acetyl-CoA: occurs in the mitochondria.
When is NAD+ needed?
is needed for the dehydrogenation of glyceraldehyde 3-phosphate, which is the first step in generating ATP for the body.
What does elevated levels of LDH be a sign of and what does the Lactate dehydrogenase?
LDH catalyses the inter-conversion of pyruvate and lactate
.
Elevated levels can be used to diagnose several disorders including:
- stroke
- heart attack
- liver disease (e.g. hepatitis)
- muscle injury
- muscular dystrophy
- pulmonary infarction
What happens when a muscle is damaged and what can this be used for?
Creatine kinase leaks into the bloodstream.
Elevated levels can be used to:
-diagnose myocardial infarction (heart attack)
-determine the extent of muscular disease
-evaluate cause of chest pain
-help discover carriers of muscular dystrophy (Duchenne)
If LDH is found in plasma what is this usually an indicator of?
Infarct/muscle injury
What does the pyruvate dehydrogenase complex consist of?
3 Enzymes:
- Pyruvate decarboxylase
- Lipoamide reducatase transacelyase
- dihydrolipoyl
5 co-factors:
- Thiamine pyrophosphate (TPP)
- Lipoamide
- FAD
- coA
- NAD+
Which enzyme binds with which prosthetic group?
pyruvate decarboxylase (E1)——thiamine pyrophosphate (TPP)
lipoamide reductase-
transacetylase (E2)——lipoamide
dihydrolipoyl dehydrogenase (E3)—–FAD (Flavine Adenine Dinucleotide)
Are all co-factors bounded permanently?
Prosthetic groups such as lipoamide are a permanent part of the complex, whereas NAD+ and other co-factors bind reversibly to enzymes.
Summarise the pyruvate dehydrogenase complex?
- Decarboxylation of pyruvate to give hydroxyethyl TPP.
- Oxidation & transfer to lipoamide to give acetylipoamide.
- Transfer of the acetyl group to CoA to give acetyl CoA.
- Regeneration of oxidised lipoamide generating FADH2
- Regeneration of oxidised FAD, by NAD+ generating NADH.
E1: pyruvate decarboxylase
E2: lipoamide reductase-transacetylase
E3: dihydrolipoyl dehydrogenase
How else can acetyl coA be generated from other molecules?
-Fatty acids: Beta oxidation
The transamination of amino acids can also generate useful metabolites.
These amino acids are degraded to pyruvate to generate acetyl coA
What is glycolysis in summary?
In glycolysis, a six-carbon molecule is progressively broken down into two, three-carbon molecules, in the process generating reduced co-factors and ATP.
what are the ways of determining which tissue is damaged
The total creatine kinase test is about 70% accurate whilst isoenzyme testing is about 90% accurate.
