Biochemistry Flashcards
Which two parts compose glycogen metabolism?
- Glycogenesis
- Glycogenolysis
What is glycogenesis?
Formation of glycogen from glucose
What is glycogenolysis?
Breakdown of glycogen to form glucose
Where is glycogen present in the body?
- Liver
- Muscle cells
What is the name given to any pathway that generates new glucose from non-carbohydrate precursors?
Gluconeogenesis
When in the day may gluconeogenesis occur in the body and why?
In the morning
Liver glycogen stores may have deplated and glucose must be obtained from other sources (fat or muscle)
Glucose molecules are joined by which linkages in a glycogen molecule?
α1-4 glycosidic links
Which molecule is found at the centre of a glycogen molecule?
Glycogenin
Why is glycogenin required?
It has catalytic activity and can add glucose to itself
This is useful because glycogen synthase (makes glycogen) cannot make glycogen from scratch and glycogenin allows for a starting glycogen point
What is the first step of glycogenesis?
Glucose is phosphorylated (using ATP) to glucose-6-phosphate
This uses hexokinase as a catalyst
When glucose-6-phosphate is produced as part of glycogenesis, which two paths can it take?
- Breakdown by glycolysis for energy
- Storage as glycogen
During the storage pathway in glycogenesis, what is the function of phosphoglucomutase?
Glucose-6-phosphate is converted to glucose-1-phosphate
When glucose-1-phosphate is produced during the storage pathway of glycogenesis, what is it then converted to and by which catalyst?
UDP-glucose
UDP-glucose pyrophsphorylase
(UTP is first phosphorylated to UDP and then added)
When UDP-glucose is formed, how is it incorporated into a glycogen molecule?
Glycogen synthase will take the glucose part of the molecule and allow it to bind to the ends of existing glycogen
What happens to the UDP part of the molecule once glucose is incorporated into glycogen?
UDP can be phosphorylated bact to UTP
Which enzyme allows branches to be added to a glycogen molecule?
Transglycosylase
It can intoduce α1-6 glycosidic branches approximately every 10 glucose residues
Which process is catalysed by glycogen phosphorylase?
Glycogenolysis
How is glucose-1-phosphate produced from glycogen during glycogenolysis?
Glycogen has one glucose cleaved
The glucose is combines with a phosphate
During glycogenolysis, how is glucose-6-phosphate produced?
Phosphoglucomutase
Where in the body will glucose-6-phosphate be dephosphorylated and released into the blood, and by which enzyme?
Liver
Glucose-6-phosphotase
Which transporter transports glucose produced from glycogen in the liver into the blood?
GLUT2
What happens to glucose-6-phosphate produced during glycogenolysis in skeletal muscle?
Glucose-6-phosphate cannot be dephosphoryated in skeletal muscle
It is used to provide energy via glycolysis and the TCA cycle
Which enzymes regulate the breakdown and reformation of glucose?
Glycogen phosphorylase - cleaves glucose from glycogen
Glycogen synthase - adds glucose (UDP glucose) to glycogen
Which hormones regulate the activity of both glycogen phosphorylase and glycogen synthase?
Insulin and glucagon
Which enzyme does insulin activate and which hormone does insulin inhibit?
Glycogen synthase
Glucagon
Which other hormones may stimulate glucagon?
Cortisol and adrenaline
What is glyconeogenesis?
The synthesis of glucose from non-carbohydrate precursors when liver glycogen is depleted and no dietary glucose is present
What are the three classes of precursors for gluconeogenesis?
- Lactate - synthesised by skeletal muscle under anaerobic conditions
- Amino acids - derived from muscle protein by proteolysis
- Glycerol - derived from triglycerides by lipolysis in adipose tissue
Which two locations in the body are the locations of gluconeogenesis?
Mainly the liver, also the kidneys
Why is gluconeogensis not the exact opposite of glycolysis?
There are three irreversible reactions in glycolysis mediated by three different enzymes
- Hexokinase - glucose to glucose-6-phosphate
- Phosphofructokinase - fructose-6-phosphate to fructose-1,6-biphosphate
- Pyruvate kinase - phosphoenolpyruvate to pyruvate
How much energy is required for gluconeogenesis to proceed?
4ATP
2GTP
During gluconeogenesis, where will lactate travel when it is produced?
Liver
How many ATP are required for gluconeogenesis?
6 ATP
(there is a net loss of 4 ATP as anerobic respiration provides 2 ATP)
Why is it useful to the muscle tissue and blood when the liver resynthesises glucose from lactate?
It prevents acidification of the blood
It takes away some of the metabolic burden from muscle tissue allowing them to function for longer
Which two classes can amino acids be grouped depending on whether they can make glucose or not?
Ketogenic - cannot be used for making new glucose
Glucogenic - can be used for making new glucose
Which points in the aerobic respiration pathway can glucogenic amino acids enter to form new glucose?
- TCA cycle (oxaloacetate must already be present for the cycle to function)
- They can form pyruvate
Regardless of the way amino acids enter the aerobic respiration pathway, what is the outcome in terms of glucose formation?
Oxaloacetate is produced either way
This produces glucose via phosphoenol-pyruvate
Gluconeogenesis is regulated at which two levels?
- Systemic by hormonal control (insulin and glucagon)
- Local at the level of individual cells
Describe the systemic regulation of gluconeogenesis involving glycagon
Gluconeogenesis is stimulated
Fructose-1,6-biphosphate is stimulated and glycolysis and phosphofructokinase are inhibted
Describe the systemic regulation of gluconeogenesis involving insulin
Insulin stimulates glycolysis
Phosphofructokinase is stimulated and gluconeogenesis and fructose-1,6-biphosphate are inhibited
In terms of local regulation of glycolysis and gluconeogenesis, what is responsible for control of these processes?
Allosteric effectors
What will stimulate glycolysis and inhibit gluconeogenesis at a local level?
High AMP, ADP or ATP will stimulate glycolysis
Fructose-2,6-biphosphate will also stimulate glycolysis when in high concentrations
What will stimulate gluconeogenesis and inhibit glycolysis at a local level?
High concentrations of citrate, alanine and acetyl-CoA will inhibit glycolysis and promote gluconeogenesis
What is the most dense energy source?
Fat
Why is fat essential to take in through diet?
- It is a key form of energy
- Some fatty acids are essential fatty acids and can only be obtained through diet
- Some vitamins are fat solube so require fat for their uptake
What are the three main types lipids?
- Simple lipids - fatty acids, triglycerides and waxes
- Compound lipids - associated with other compound groups e.g. lipoproteins
- Steroids - cholesterol, steroid hormones
What is the main energy form within adipose tissue?
Triglycerides
Fatty acids have three classifications depending on the structure of the molecule - what are these?
- Saturated - no double bonds
- Unsaturated - one double bond between carbons
- Polyunsaturated - several double bonds between carbon atoms
Double bonds are usually in what configuration?
Cis
Trans fats are usually in which structural configuration?
Trans
What is the consequence of trans fats having a trans molecular structure?
They can be packed less tightly
What are the main naturl fatty acids?
Palmitic acid - saturated 16 carbons
Stearic acid - saturated 18 carbons
Oleic acid - same as steric acid but includes a doube bond
How can essential fatty acids be recognised?
The body can only synthesise polyunsaturated fatty acids with double bonds up to nine carbons away from the carboxyl group
Any fatty acid that exceeds this rule is an essential fatty acid
What are the two methods for naming fatty acids?
- The carboxyl group can be counted as carbon 1
- The carbon furthest from the carboxyl group is counted as carbon 1 (or the omega (ω) carbon) an the carbon closest is the α carbon
Expain what is meant by an omega 3 fatty acid
There is a double bond 3 carbons away from the omega carbon
Why are plant fats generally oils at room temperature, whilst animal fats are solids?
Plant fats are much more unstaurated so their melting point is much lower
What are the products of fat digestion in the small intestine?
- Glycerol - readily absorbed into the intestinal epithelium
- Fatty acids
- Monoglycerides
How does the absorption of short and long chain fatty acids differ?
Short chains can enter the portal blod directly
Long chains (and monoglycerides) are first resynthesised into triglycerides, coated with phospholipids, protein and cholesterol to form chylomicrons - they can then enter the lymphatic system
What can happen to free fatty acids in the blood?
- They can be resynthesised to triglycerides for storage
- They can be oxidised to produce a huge amount of energy
What is lipolysis?
The breakdown of lipids stored in adipose tissue
What must fatty acids be converted into in order for them to slot into the TCA cycle?
CoA derivatives
Where does the conversion of fatty acids to CoA derivatives fit into the TCA cycle within the cell?
Cytoplasm
(Fatty acid + CoA → Acyl-CoA)
After oxididation in the cytoplasm of fatty acids, where does further oxidation take place?
Mitochondrial matrix
By which process is acyl-CoA carried into the mitochondria?
Carnitine shuttle
How is acyl-CoA transported into the mitochondrial matrix via the Cartinine shuttle?
- Fatty acid transferred from CoA to cartinine
- Acyl-cartinine transported actoss membrane to matrix
- Acyl group cleaved off in matrix
- Acyl group recomines with a CoA
- Cartinine is moved out and the cycle can start again
Where does β oxidation occur?
Mitochondrial matrix
What are the products of β oxidation?
- Acetyl-CoA
- Acyl-CoA (shortened by 2 carbons)
- FADH2
- NADH
- H+
What happens to the shortened acyl-CoA molecule after β oxidation?
It can re-enter the β oxidation cycle to produce more acetyl-CoA
Subsequent to β oxidation, what is the yield from one acetyl-CoA molecule in the TCA cycle?
- 1 FADH2
- 3 NADH
- 3 H+
- 1 GTP
What is the P/O ratio?
Phosphate/oxygen ratio
This is the amount of ATP produced from the movement of two electrons through a defined electron transport chain donated by the reduction of an oxygen atom to water
What is the P/O ratio for FADH2?
1.5
What is the P/O ratio for NADH?
2.5
How much ATP, in total, will be produced from steric acid which can be cleaved 8 times to produce 9 acetyl-CoA
- 9 GTP
- 27 + 8 = 35 NADH
- 27 + 8 = 35 H+
- 9 + 8 = 17 FADH2
(9 (GTP + ( 35x 2.5) + (17 x 1.5) - 2 (activation)) = 120 ATP
Where can glycerol be activated and what will it be activated to?
Liver and kidneys (not present in adipose tissue)
Glycerol-3-phosphate (by glycerol kinase)
When gycerol-3-phosphate is produced what is it converted to in order for it to begin glycolysis?
Dihydroxyacetone phosphate
(by glycerol phosphate dehydrogenase)
This can then be converted into one of the intermediates of gycolysis
Where do ketone bodies originate?
β oxidation of fatty acids
Formed in liver mitochondria
What are the three ketone bodies?
- Acetoacetate
- Acetone
- Hydroxy-butyrate
How are ketone bodies useful for energy production?
They can enter the TCA cycle in peripheral tissues and heart muscle and be resyntheised into acetyl-CoA
Why and when may ketone bodies become dangerous?
During periods of starvation
Much oxaloacetate is used up for gluconeogenesis, this means ketone bodies are produced from excess acetyl-CoA
Ketone levels rise in the blood and this can cause acidosis affecting the CNS and heart
Acidotic coma or death may occur
What is the treatment for ketosis in starvation or diabetes?
Administration of insulin to prompt glucose breakdown
(glucose may also me given)
What is lipogenesis?
When new fatty acids are synthesised when there is surplus energy
In which tissues can lipogenesis occur?
Liver, kidneys, mammary glands and brain
By which protein are free fatty acids transported into the plasma?
Albumin
Excess carbohydrate is used to form fatty acids and triglycerides in the liver, what is used to transport these triglycerides to adipose tissue for storage?
Low density lipoprotein
What can happen to fatty acids when they are produced? (2)
- Esterified with glycerol to form triglycerides
- Oxidised to allow acetyl-CoA to be resynthesised again
Lipogenesis occurs in th cytoplasm of which cells?
Liver
What is the substrate for lipogenesis?
Acetyl-CoA
Where is acetyl-CoA produced and by action of which enzyme?
Mitochondrial matrix
Pyruvate dehydrogenase
How does acetyl-CoA cross the inner mitochondrial membrane for lipogenesis?
It bind to citric acid allowing it to cross the membrane
Which regulatory enzyme controls how much fatty acid is synthesised at any one time?
Acetyl-CoA carboxylase
(found in liver and adipose tissue)
When effect does acetyl-CoA carboxylase have on acetyl-CoA?
It converts acetyl-CoA to malonyl-CoA by adding bicarbonate
This uses 1 ATP
What is the purpose of malonyl-CoA in terms of fatty acid synthesis?
It will donate the addition carbon (from bicarbonate) to the fatty acid
Which enzyme catalyses fatty acid synthesis?
Fatty acid synthase
Describe how fatty acid synthase facilitates fatty acid synthesis
- There are two acyl binding sites - one for acetyl-CoA and one for malonyl-CoA
- 2 carbons are transferred from malonyl-CoA to acetyl-CoA
- The second acyl binding site becomes free and a new malonyl-CoA is added and the cycle repeats
- The fatty acid chain develops 2 carbons at a time and remains attaced to fatty acid synthase
As well as acetyl-CoA and malonyl-CoA, what else does fatty acid synthase require in order to function?
NADPH
An electron donor (this is a reductive process)
At what chain length is the fatty acid released from fatty acid synthase and what is the name of this fatty acid?
Palmitic acid
(this is th maximum chain length fatty acid synthase can synthesise)
Which enzyme confers control of fatty acid metabolism?
Acetyl-CoA carboxylase
Which hormones can influence acetyl-CoA carboxylase and what will their effects be on it?
Insulin - stimulate
Glucagon - inhibit
Adrenaline - inhibit
(fatty acid synthesis ony occurs in times of plentiful resources)
What can antagonise acetyl-CoA carboxylase when its levels are high?
Palmitoyl CoA
(abundant when fatty acids are in excess)
If glycerol-3-phosphate is required for triglyceride synthesis, how may it be synthesised?
Glycerol kinase
(found in the liver)
Fat cells do not have glycerol kinase - how do they obtain glycerol-3-phosphate?
Via glycolysis
In fat cells, why is it virtually impossible to synthesise triglycerides unless there is plenty of glucose in the bloodstream?
- Glycerol-3-phosphate is essential for triglyceride synthesis with fatty acids
- It can only be obtained in fat cells via glycolysis
- Glycolysis can only occur if glucose is present
Why are amino acids which are not used for protein synthesis degraded and used to provide energy?
They are not easily stored
Where does amino acid breakdown primarily occur?
Liver
Which two sources can amino acids be obtained from?
- Dietary intake
- Cellular protein turnover
How do tissues which require amino acids access them?
Bloodstream
What must be removed from amino acids in order to form the intermediates required for them to slot into the TCA cycle?
Nitrogen
(from amino groups)
What are the breakdown products from amino acids and why is it important that they are excreted?
Ammonia and ammonium ions
In high concentrations these can be toxic
How are by products containing notrogen mainly excreted from the body?
Urea in the urine
Where is urea formed?
Liver
What are the headings for the three stages of urea synthesis?
- Transamination
- De-amination
- Urea (Ornithine) cycle
Describe the process of transamination
The amino group is transferred to a keto acid
This can occur in all tissues and usually forms glutamic acid presuming ketoglutarate is used as the keto acid
Describe the process of de-amination
The amino group is removed from the glutamic acid reforming the keto acid
The free ammonium ion can now enter the urea cycle
Describe the urea cycle
Free ammonium ions are converted to urea along with aspartic acid
Urea has two nitrogen atoms and obtains one from each of urea and aspartic acid
Where does de-amination occur?
Liver
How can the amino group of glutamate be transported to the liver for deamination?
The amino group is transferred fro glutamate to pyruvate to produce alanine
Alternatively, glutamine synthase can add ammonium ions to glutamate to produce glutamine
Both alanine and glutamine can be transported to the liver
Demaination is an energy producing process
True or false?
False
It is energy consuming (3ATP)
As well as urea, 2 phosphate, 2 ADP and AMP, what else is produced during demaination?
Fumarate
It is an intermediate in the TCA cycle
What is the resulting structure called when the amino group is removed?
Carbon skeleton
What is the fate of carbon skeletons? (2)
- Degraded to glucose
- Oxidised in the TCA cycle
What are the two types of amino acids that can be broken down?
- Ketogenic amino acids
- Glucogenic amino acids
What is a ketogenic amino acid broken down into?
Acetyl-CoA or acetoacetyl-CoA
This can give rise to ketone bodies or fatty acids as well as entering the TCA cycle
What is a glucogenic amino acid broken down into?
Pyruvate or TCA cycle intermediates
They can be converted into phosphoenolpyruvate and then into glucose to allow for glycolysis
Alcaptonuria involves a blockage in the degredation of _______________ and ___________
Phenylalanine to tyrosine
What is maple syrup urine disease and what causes it?
The urine is sweet and smells like maple syrup
The degredation of valine, isoleucine and leucine is blocked
Mental and physical retardation can be found in some patients yet this can be controlled through diet
What is phenylketonuria?
PKU is due to a failure of the degredation of phenylalanine to tyrosine
It causes severe mental retardation if untreated because phenylalanine can build up in all body tissues and fluids
The treatment is a low phenylalanine diet
What may happen in a urea cycle disorder where α-ketoglutarate levels become low?
Not enough α-ketoglutarate is present to bind to free ammonium ions leading to a rise that is potentially toxic - especially to the nervous system
