Biochemistry Flashcards
What is glycogenolysis?
The breakdown of glycogen to form glucose. It is accomplished by phosphorylis.
What is the main storage form of glucose in the liver and muscle cells?
Glycogen
When is liver glycogen broken down?
In between meals
What is liver glycogen released to maintain?
Blood glucose levels for red blood cells and the brain
What type of glycogen can only be consumed within the muscle cells?
Muscle glycogen
Where can muscle cells not release glycogen into?
The blood stream
What provides energy via glycolysis and the TCA cycle during bursts of physical activity?
Muscle glycogen
What does glycogenolysis fluctuate depending upon?
Meal times
What is the name of the pathway which generates new glucose from non-carbohydrate precursors?
Gluconeogenesis
What is the primary source of glucose overnight when hepatic glycogen is depleted?
Gluconeogenesis
What is a polymer consisting of single glucose molecules linked together to form chains?
Glycogen
What are glycogen molecules joined by?
An alpha 1-4 glycosidic link.
What are the branches of glycogen introduced by?
Alpha 1-6- glycosidic link.
How are new molecules added, and old molecules cleaved off from glycogen?
Free glucose joins onot the ends and glucose molecules are cleaved off the ends
What can glucose residues only be added to?
An existing glycogen chain.
What protein is found in the centre of glycogen?
Glycogenin
What substance has a catalytic activity which adds small number of glucose molecules to itself?
Glycogenin
What is the enzyme which synthesises glycogen?
Glycogensythase
What is a glycogen primer containing at least 4 glucose residues covalantly attached to?
Glycogenin
What has to first happen to glucose before it can be used for any further metabolic pathways?
It has to be phosphorylated
What is glucose phosphorylated to?
Glucose-6-phosphate
What, in the initial pathway of glycogen synthesis, traps the glucose in the cell?
Phosphorylation of glucose to glucose-6-phosphate
Once glucose has been trapped in the cell, by phosphorylation of glucose to glucose-6-phosphate - what two choices does the cell have?
If cell needs energy it can breakdown glucose-6-phosphate in glycolysis, however if plenty of glucose is present then glucose-6-phosphate can be used for the synthesis of glycogen.
Once it has been decided that glucose-6-phosphate will synthesise glycogen, what is the initial step?
Glucose-6-phosphate has to be converted to glucose-1-phosphate
What catalyses glucose-6-phosphate to glucose-1-phosphate?
Phosphoglucomutase
In the synthesis of glycogen, once glucose-6-phosphate is converted to glucose-1-phosphate by phosphoglucomutase, what then happens to the glucose-1-phosphate?
It has to be activated to form UDP-glucose
What can be considered an actived form of glucose and acts as a substrate for glycogen synthase?
UDP-glucose
In the synthesis of glycogen, once UDP-glucose is activated, what does glycogen synthase do to it?
Takes the glucose part of UDP-glucose and covalently bonds it ontop hte ends of existing glycogen.
In glycogen synthesis, what happens to the UDP that is left over, once glycogen synthase has taken the glucose part away from it?
It is phosphorylated again to form UTP
How much ATP does the phosphorylation of UDP to UTP consume?
1 ATP
For each glucose that is added to glycogen, how much ATP is consumed?
1
In glycogen synthesis, what converts glucose-1-phosphate to UDP-glucose?
UDP-glucose pyrophosphorylase
What is a nucleotide like ADP and has a uricil base, ribose sugar and 2 phosphate groups?
UDP
What makes the glucose in UDP highly active?
Attached to the second phosphate group is glucose and the bond between them makes glucose highly active.
What is - simple precursors are first converted to activated intermediates - a common pathway of?
Biosynthetic pathways
What is an activated form of phosphate?
ADP
What is an activated form of acetate?
Acetyl-CoA
What does the phosphate ester linkage in a nucleotide sugar release on hydrolysis?
Free energy
What enzyme adds on one glucose molecule (from UDP-glucose) onto the end of glycogen at one time?
Glycogen synthase
What is the rate-limiting enzyme of glycogenesis?
Glycogen synthase
What branching enzyme, introduces alpha 1-6 glycosidic branches onto glycogen?
Transglycosylase
Approximatly how many glucose residues apart is an alpha 1-6 glycosidic branched added?
10
If we need glucose, then how can muscle and liver cells remove glucose from its stored form?
By using glycogenolysis
What enzyme catalyses glycogenolysis?
Glycogen phosphorylase
What enzyme takes a glycogen molecule and cleaves one glucose off the end and adds a phosphate group to it?
Glycogen phosphorylase
What is the product of glycogen breakdown?
Glucose-phosphate
In glycogenolysis, what is glucose-1-phosphate converted to?
Glucose-6-phosphate
Where in the body, can glucose-6-phosphate be dephosphorylated and the resulting glucose released into the blood stream?
Liver
In skeletal muscle, glucose-6-phosphate cannot be dephosphorylated, so how can it provide energy?
Via glycolysis and the TCA cycle (debranching requires additional enzymes)
What transporter removes glucose from liver into blood?
GLUT2 transporter
What regulates glucogenesis and what regulates glycogenolysis
Glucogenesis - glycogen synthase
Gluconeolysis - Glycogen phosphorylase
What is the hormone of the fed state, and what does it signal the availability of?
Insulin - availability of carbohydrate in the blood stream
What does insulin stimulate the synthesis of?
Glycogen and glycogen synthase
What does insulin inhibit, at the same time as producing glycogen synthase?
Glycogen phosphorylase
What is the hormone of the starving state and what does it signal?
Glucagon - signals lack of glucose in the blood stream
What will glucagon stimulate and what will it inhibit?
Stimulate glycogenolysis and glycogen-phosphorylase
What does glucagon inhibit at the same time as stimulating glycogen-phosphorylase?
Glycogen synthase
What two other substances stimulate glycogen phosphorylase?
Adrenaline and cortisol
What diseases have increased glycogen deposits in the liver or muscle or both and each type is due to a defect in a different enzyme?
Glycogen storage diseases
What is glycogenesis?
Synthesis of glycogen from freely available glucose)
What are the three non-carbohydrate precursors for gluconeogenesis?
- Lactate (lactic acid)
- Amino acids
- Glycerol
What is produced by skeletal muscles under anaerobic conditions?
Lactate
When skeletal muscle works hard and blood cannot supply sufficient oxygen for oxygen phosphorylation, what will muscle do?
Conduct glycolysis under anaerobic conditions
During glycolysis under anaerobic conditions in skeletal muscles, what does the muscle do to re-oxidise its NADH to NAD+?
It will convert pyruvate to lactic acid
How are amino acids derived from muscle protein?
By proteolysis
What is glycerol derived from?
Triglycerides (fat storage molecules)
What does lipolysis in adipose tissue produce?
Glycerol
Gluconeogenesis is very energy consuming - where does the energy come from?
Re-oxidation of stored molecules
Where does gluconeogenesis occur?
In the liver
What are the two main methods the liver used to keep the blood sugar levels constant?
- Gluconeogenesis
2. Glycogen synthesis
Where are small amounts of glucose always synthesised?
In the kidneys
What does the energy from oxidation of fatty acids released from adipose tissue supply?
Gluconeogenesis
What three enzymes catalyse the three irreversible reactions in glycolysis?
- Hexokinase
- Phosphofructokinase
- Pyruvate kinase
Gluconeogenesis requires 4 unique liver enzymes as well as proceeding via the synthesis of what?
Oxaloacetate in mitochondria
During stage 1 of glycolysis, what converts glucose to glucose-6-phosphate?
Hexokinase
In the first stage of glycolysis, what enzyme catalyses the reversible conversion of glucose-6-phosphate to fructose-6-phosphate?
Phosphoglucose isomerase
In stage 1 of glycolysis, what occurs after the conversion of glucose-6-phosphate to fructose-6-phosphate via phosphoglucose isomerase?
Fructose-6-phosphate converts to Fructose-1,6,-bisphosphate
What enzyme catalyses the irreversible reaction during stage 1 glycolysis, of fructose-6-phosphate to fructose-1,6-bisphosphate?
Phosphofructokinase
Gluconeogenesis is energetically expensive - how much ATP is required?
6ATP
In gluconeogenesis what drives an unfavourable reaction?
ATP hydrolyses
How many pyruvates are needed to make glucose?
2
What are the two componenets of the 6ATP that are consumed to make one glucose in gluconeogenesis?
4ATP
2GTP
How much ATP is generated by glycolysis for each glucose that is oxidised?
2ATP
State the overall equation for gluconeogenesis?
2 pyruvate + 4ATP + 2GTP + 2NADH + (4H+) + 6H2O
glucose + 4ADP +2GDP + 6Pi + (2NAD+) + 2H+
Lactic acid is generated in muscle (by anaerobic exercise) - what does the muscle convert?
Pyruvate to generate ATP
To be able to continue glycolysis (in skeletal muscle anaerobic exercise), what happens to the pyruvate formed from glucose?
It is converted to lactic acid which regenerates ADP+
Why can lactic acid be so easily transported into the blood stream?
Because it is a polar molecule
Once the lactic acid is in the blood stream, after anaerobic exercise, where does it then go?
To the liver
What happens to lactic acid in the liver?
It is converted back to pyruvate and then back to glucose (costing 6ATP)
What is the Cori cycle?
- Glycolysis in muscle breaking down glucose to lactate
- Lactate moving to liver to be broken down to glucose (gluconeogenesis)
- Glucose moved back to muscle for repeat of cycle
What are the two groups of amino acids?
- Ketogenic
2. Glucogenic
What group of amino acids cannot be used for making glucose, and what group can be used as they serve as precursors for gluconeogenesis?
Ketogenic - cannot
Glucogenic - can
Where do all the glucogenic amino acids involved in gluconeogenesis enter, or become converted to?
The TCA cycle or converted to pyruvate
What does the first reaction in gluconeogenesis convert?
Pyruvate to oxaloacetate
What does gluconeogenesis proceed by?
Oxaloacetate
What can any molecule that enters the TCA cycle in one of the lower intermediates lead to the formation of?
Oxaloacetate which can then be used for glucose synthesis
What can any molecule that is converted to pyruvate also be directly converted to?
Oxaloacetate
What are ketogenic amino acids converted to?
Acetoacetyl CoA
What are the rules for ketogenic amino acids entering the TCA cycle?
- Have to be converted to acetoacetyl CoA
2. Only enter if oxaloacetate is already present
What would happen if gluconeogenesis removed oxaloacetate?
Then TCA cycle cannot further accept acetyl groups
What does glucagon signal a need for glucose in? (Pathway is related to glycolysis)?
Gluconeogenesis
In gluconeogenesis, what does glucagon stimulate?
Fructose 1,6-bisphosphatase
As well as glucagon stimulating gluconeogenesis and fructose 1,6-bisphosphatase - what else does it inhibit?
Glycolysis
Because insulin signals the availability of glucose, what does it therefore inhibit and stimulate?
Inhibits Gluconeogenesis and stimulates glycolysis
What two levels are glycolysis and gluconeogenisis regulated at?
System level - done by hormones
Individual cellular - done by allosteric effectos
What two molecules signal the requirement for energy in individual cell level regulation?
AMP or ADP
In regulation of glycolysis and gluconeogenesis, what does the stimulation of AMP or ADP cause?
Breakdown of glucose which leasd to generation of energy
What do AMP or ADP inhibit, at cellular regulation of glycolysis and gluconeogenesis?
Gluconeogenesis - energy expensive process
What happens to glycolysis and gluconeogenesis in the company of ATP?
Switch off glycolysis and stimulate gluconeogenesis
What is an intermediate of glycolysis, and is in high concentrations in the fed state and low concentrations in the starved state?
Fructose-2,6-bisphosphate
What does fructose-2,6-bisphosphate stimulate and inhibit?
Stimulates - glycolysis at high concentrations
Inhibits - gluconeogenesis
What are citric acid, alanine and acetyl CoA all important for?
Precursor molecules for biosynthetic processes
What do high concentrations of citric acid, alanne and acetyl CoA stimulate and inhibit?
Stimulate gluconeogenesis and inhibit glycolysis
What does glycolysis start and end with?
What does gluconeogenesis start and end with?
Glycolysis starts with glucose and ends with pyruvate
Gluconeogenesis starts with pyruvate and ends with glucose
In gluconeogenesis, what is the first product of the first reaction starting with pyruvate?
Oxaloacetate
What is an intermediate in the TCA cycle and is the 1-4 carbon molecule that accepts the acetyl groups in the very first step of TCA cycle?
Oxaloacetate
What are the 4 specific enzymes which are required to bypass the irreversible reactions in glycolysis?
- Pyruvate carboxylase
- PEP carboxykinase
- Fructose-1,6-bisphosphatase
- Glucose-6-phosphatase
Where does lactate enter the gluconeogenesis pathway?
Pyruvate
Where do amino acids enter the gluconeogenesis pathway?
Pyruvate and oxaloacetate (mitochondrial matrix)
Where does glycerol enter the gluconeogenesis pathway?
Dihydroxyacetone-P (before converting to fructose-1,6-bisP)
What does glucose-6-phosphatase convert?
Glucose-6-phosphate to glucose
What does fructose-1,6-bisphosphatase convert?
Fructose-1,6-bisphosphate to fructose-6-phosphate
What does pyruvate carboxylase convert in gluconeogenesis?
Pyruvate to oxaloacetate
What does PEP carboxykinase convert in gluconeogenesis?
Oxaloacetate to PEP
What is associated with disease but is also important because it is an energy source?
Fat metabolism
What are essential fatty acids?
Fatty acids that cannot be sythesised un our body
Give an example of essential fatty acids?
Polyunsaturated fatty esential fatty acids
What 4 vitamins are associated with fat?
A, D, K, E
What are the three classes of lipids?
- Simple
- Compound
- Steroids
Give two examples of simple lipids?
Fatty acids and triglycerides
Give 5 examples of compound lipids?
- Phosphate groups
- Phospholipids
- Carbohydrates
- Glycolipids
- Lipoproteins
Give two examples of steroid lipids?
- Steroid hormones
2. Cholesterol
What are predominantly hydrocarbons?
Lipids
Are lipids insolbule or soluble?
Insoluble
What are the main energy forms in adipose tissue?
Triglycerides
Why can fat be stored without lots of water arround?
Its hydrophobic nature
What are the 3 hydroxyl groups of glycerol esterified with to produce triglyceride?
Fatty acid
What are straight chains and aliphatic (no rings)?
Fatty acids
Do fatty acids usually contain an even number of carbon atoms or an odd number?
Even number (2-20)
What are the three types of fatty acids?
- Saturated
- Unsaturated
- Polyunsaturated
What is a fatty acid with no double bonds?
Saturated
What is a fatty acid with a single double bond?
Unsaturated
What formation are fatty acid double bonds in?
Cis
What are the three main fatty acids?
- Palmitic acid (16:0)
- Stearic acid (18:0)
- Oleic acid (18:1)
(16:0) - what is the first number and what is the second number?
First number is number of carbons
Second number is number of double bonds
What can our body not make double bonds further away than?
9 carbons from the carboxyl group of the fatty acid
What are polyunsaturated fatty acids with double bonds further away than 9 carbons from carboxyl end called?
Essential fatty acids
How many carbons does Linoleic acid have and how many double bonds?
18:2
In greek nomenclature for fatty acids, what is the carbon adjacent to the carboxyl molecule called and what is the furtheset away called?
The alpha carbon
The omega carbon
What are fatty acids with up to 8 carbons like at room temperature?
Liquids
What is an alcohol that is readily absorbed into the epithelial cells of the intestine?
Glycerol
Fatty acids which are short can directly enter the portal blood, what happens to longer chain and monoglycerides?
Manipulated first
What do epithelial cells re-synthesise the fatty acids and monoglycerides back into?
Triglycerides
In fat absoprtion, once epithelial cells have re-synthesised the fatty acids and monoglycerides back into triglycerides, what are the triglycerides then coated with that makes them transportable in the blood stream?
Proteins, phospholipids and cholesterol
In fat absorption, what are teh complexes consiting of absorbed triglyceride and protein phjospholipid cholesterol termed?
Chylomicrons
What are chylomicrons a type of?
Lipoprotein
What are the three main products of fat digestion?
Glycerol (readily absorbed in intestinal epithelial cells)
Fatty acids
Monoglycerides
What is a way of transporting dietary fat through the human body?
Chylomicrons
What happens to chhylomicrons when they reach any tissue wich requires fats?
They are attacked by lipoprotein lipases and these lipoprotein lipases cleave the triglycerides within the chylomicrons.
At target tissues, what happens to the fatty acids?
They are either again re-synthesised into triglycerides for example for storage in fat cells, or can be oxidised in muscle cells
What do hormone sensitive lipases catalyse?
LIPOLYSIS
What does the initial cleavage of fat?
Hormone sensitive lipases (adrenaline-sensitive)
Before fatty acids can be oxidised, they have to be activated, how does this occur?
By linking the fatty acid to co-enzyme A
Where does the process of linking the fatty acid to co-enzyme A to activate it occur?
In the cytoplasm of cells
How much ATP is needed to link fatty acids to CoA?
2ATP
What two things is acel coA formed from?
Fatty acid linked to CoA
Where does further oxidation of fatty acids occur?
In the mitochondrial matrix
What specific carrier, transports acyl CoA from the cytoplasm to the mitochondrial matrix for further oxidation?
Carnitine shuttle
Explain the carnitine shuttle
- In cytoplasm the fatty acid of the acyl CoA is transferred onto a carrier protein called carnitine, forming acyl carnitine
- Acyl carnitine now can be transported by a specific transporter molecule across the inner mitochondrial membrane into the matrix.
- On the matrix side of the mitochondrial, the acyl group is cleaved off the acyl carnitine and again transferred onto a CoA coenzyme.
- The resulting carnitine is moved out again and the cycle can continue.
In the carnitine shuttle, what molecules are never transported across the membrane?
CoA molecules - the pools in the cytoplasm and matrix remain seperate
Where does beta-oxidation occur?
In the mitochondrial matrix
The type of process is beta-oxidation?
An oxidative
What does the cycle of reactions that is beta-oxidation, take as its substrate?
Acyl CoA
In beta-oxidation, once the acyl CoA has been transported into the mitochondrial matrix by carnitine, what happens to the aceyl CoA?
It is shortened by two carbons in a serioes of four reactions.
In beta-oxidation, as a result of the four reactions which shorted acyl CoA by two carbons, what is produced?
One acetyl CoA and a second product is a new acyl CoA which is shortened by two carbons
Within the 4 steps in beta-oxidation, how many reactions are oxidation reactions?
2
In beta-oxidation, electrons are removed from the substrate and tehse electrons are transferred onto electron carriers, and in this case what 2 substances are required?
1 FAD and 1 NAD
What 4 substances are generated in one round of beta-oxidation?
- FADH
- NADH
- 1 Acetyl CoA
- Shortened acyl CoA
The circle of reactions in beta-oxidation takes as long as it needs to to convert what?
Acyl CoA into acetyl CoA parts
After the last cycle of the beta-oxidation pathway, what is formed?
2 Acetyl CoAs
Give the four products of each cycle in beta-oxidation?
- 1 acetyl-CoA
- 1 FADH2
- 1 NADH + H+
- 1 fatty acyl-CoA, shortened by 2 carbon atoms
To cut an 18 fatty acid into 9, 2 carbon chunks, how many cutting actions are needed and so how many cycles in beta-oxidation occur?
8 cutting actions and so repeated 8 times
In beta-oxidation, what do the products of one cycle FAD2 and NADH generate?
ATP
When 8 cycles of the beta-oxidation pathway occur, how many FADH, NADH and acetyl CoA molecules are produced?
FADH - 8
NADH - 8
Acetyl CoA molecules - 9
Once beta-oxidation has produced acetyl CoA molecules, what happens to them?
Completely oxidised in the TCA cycle
What are acetyl-CoA molecules oxidised to in the TCA cycle?
CO2
What does 1 round of the citric acid cycle produce?
1 FADH2
3 NADH + H
1 GTP
What is used to calculate how many ATP in total can be obtained from the oxidation of an acid?
Use the p/o ratio (amount of ATP we can obtain for the reduction of a single oxygen atom to water)
What is the p/o ratio for FAD?
1.5
What is the p/o ratio for NADH?
2.5
What two substances from beta-oxidation are used for ATP generation in oxidative phosphorylation?
FADH and NADH + H
If beta oxidation produces 8 FADH2, 8 NADH + 8H+ and 9 acetyl-CoA, what is the total ATP yield? (hint* remember acetyl-CoA is oxidised in TCA cycle)
:9 acetyl-CoA makes 9 FADH2, 27 NADH + 27H+, 9 GTP
FADH2 NADH GTP (2 from activation step)
[17 x 1.5] + [35 x 2.5] + [9 - 2] = 120 ATP
Unsaturated fatty acids are already partially oxidised, so what do they yield less of?
FADH2
What do odd chain fatty acids yield in last step, and what is it converted to, then where does it enter?
Yield propionyl-CoA (3 carbons), converted to succinyl-CoA, enters TCA cycle directly
In branched chain fatty acids, what is C-1 oxidised to, and what can be said about the amount of acetyl- and propionyl CoA released?
Oxidised to CO2
Released in equal numbers
What can glycerol be phosphorylated to?
Glycerol-3-phosphate
What does glycerol kinase do to glycerol?
Activates it into glycerol-3-phosphate
Where is glycerol-3-phosphate present in?
Liver and kidney
In the breakdown of glycerol, what happens to the activated glycerol-3-phospate?
Dehydrogenated to dihydroxyacetone phosphate
What catalyses glycerol-3-phosphate to dihydroxyacetone phosphate?
Glycerol phosphate dehydrogenase
What are associated with the breakdown of fats by beta-oxidation?
Ketone bodies
What are ketone bodies derived from?
Acetyl CoA
Name 3 ketone groups?
- Acetoacetate
- Acetone
- Hydroxybutyrate
Where is the production of ketone bodies normally occur?
In liver mitochondria
Why can ketone bodies easily diffuse into the blood stream?
Because they are hydrophilic molecules (polar)
What happens when peripheral tissues pick up ketone bodies?
Convert them back into acetyl CoA and make them enter the TCA cycle where they are oxidised
In what two states can ketone bodies produce problems?
In starvation and uncontrolled diabetes
What two muscles in particular are ketone bodies an important source of energy for?
Heart
Renal cortex
What step of which pathway does this occur in: A C4 compound called oxaloacetate is linked to the acetyl group from acetyl CoA, forming citric acid?
First step of TCA
In starvation and uncontrolled diabetes, what happens to oxaloacetate?
It is consumed for gluconeogenesis
During starvation and uncontrolled diabetes, what does the liver produce which leads to the removal of oxaloacetate from the cell?
Glucose
In ketosis in starvation and diabetes: Synthesis of glucose costs energy, so where is this provided from?
Beta-oxidation of fatty acids
In ketosis in starvation and diabetes: what happens to the excess acetyl Co-A from increased beta-oxidation of fatty acids?
Converted to ketone bodies
What does the accumulation of ketone bodies in the blood lead to?
Acidosis
In diabetic ketoacidosis, what can be smelt on the breath?
Acetone
What is the main organ for the conversion of dietary carbohydrate into fatty acids?
The liver
Does lipogenesis act during food shortage times?
No
What are free fatty acids transported bound to?
Albumin
How are triglycerides formed in the liver transported in the blood?
In the form of a lipoprotein called VLDL
What is the opposite of beta-oxidation?
The genesis of new fatty acids - a reductive process
What is required for the synthesis of fatty acids?
Electrons
Why is lipogenesis a reductive process?
Because electrons are required
During the process of how dietary starch is converted into stored triglyceride: what is dietary starch first converted to?
Acetyl-CoA
What is the precursor molecules for the conversion of dietary carbohydrate into fatty acids?
Acetyl-CoA
Once fatty acid synthesis has started with acetyl-CoA and formed fattya cids, what are these fatty acids esterified with?
Glycerol to form triglycerides
Where does the synthesis of fatty acids from acetyl-CoA occur in?
The cytoplasm of liver cells
Where and from what is acetyl-coA generated?
In the mitochondrial matrix by dehydrogenase complex
What is the inner mitochondrail membrane impermeable to?
Acetyl-CoA, so acetyl-CoA cannot easily escape from the mitochondrial matrix to the cytoplasm.
When present at high concentrations, where is citrate transported to?
The cytoplasm
If acetyl-CoA is present in high concentrations in the mitochondrial matrix then what will this lead to?
An increase in the citric acid concentration in the mitochondria.
What is the vital first step, before fatty acids can be synthesised from acetyl-CoA?
Activation of acetly-CoA to malonyl CoA by acetyl-CoA carboxylase
Where is acetly-CoA carboxylase mainly expressed?
In the liver and adipose tissue and is an essential regulatory enzyme.
What does acetyl-CoA carboxylase decide?
How much fatty acid is synthesised at any time
What does malonyl-CoA donate?
Carbon atoms to new lipids
What enzyme takes away an acetyl-CoA and adds on an additional third carbon molecule to the acetly group?
Acetyl-CoA carboxylase
What enzyme makes a three carbon malonyl group out of a two carbon acetyl group and some bicarbonate, and how much energy is required?
Acetyl-CoA carboxylase
1 ATP consumed for each acetyl-CoA that is converted to malonyl-CoA
The carbon that ends up in the fatty acid is derived from what - malonyl-CoA or Acetyl-CoA?
Malonyl CoA
What is fatty acid synthesis catalysed by?
Fatty acid synthase
What does fatty acid synthase do to acetyl-CoA and malonyl-CoA?
Converts carbon on these molecules to long chain fatty acids. It makes only saturated straight chain fatty acids.
What molecule provides the source of electrons (reduction process) for fatty acid synthesis?
NADPH
What is a dimer and consists of two identical subunits of the same polypeptide?
Fatty acid synthase
How many different reactions can fatty acid synthase catalyse?
7
What does fatty acid synthase contain within its peptides?
Acyl carrier protein (ACP)
What part of fatty acid synthase carriers the growing fatty acid chain during synthesis?
Acyl Carrier Protein
In the first step of fatty acid synthesis, what is one acyl carrier protein load with and what does it form?
What does the second acyl carrier protein get loaded with?
An acetly group forming acetyl-CoA
Malonyl group from malonyl-CoA
In the first cycle of reactions in fatty acid synthesis, what are two carbon atoms from the malonyl-CoA transferred onto?
The acetyl group and that then turns it into a four carbon fatty acyl chain.
What occurs in each cycle of initial reactions in fatty acid synthesis?
Adds two carbons to the growing fatty acid chain and these two carbon atoms are always derived from a malonyl-CoA.
What is the growing fatty acid always attached to?
The acyl carrier protein until it is completely finished
In intial cycle of reactions in fatty acid synthesis, how long to the cycles repeat for?
Until the growing acyl chain has reached 16 carbons
Once the fatty acid has reached 16 carbons, what happens to it?
It is released from the acyl carrier protein
What are the two precursors in fatty acid synthesis?
Acetyl-CoA and malonyl-CoA
What is the longest fatty acid made by fatty acid synthase?
Palmitic (16C)
What enzyme does the control of fatty acid synthesis occur in and what does it catalyse?
Acetyl-CoA carboxylase
Catalyses the fromation of malonyl-CoA from acetyl-CoA
When is sythesis of fatty acids maximal?
When carbohydrate and energy are plentiful, and when fatty acids are scarce
How many hormones regulate acetyl-CoA carboxylase?
3
What does the secretion of insulin stimulated?
Acetly-CoA carboxylase
What does glucagon stimulate in relation to fatty acids?
Switches off fatty acid synthesis
Name a hormone other than glucagon which signals the requirement of energy?
Epinephrine/adrenaline
What does epinephrine inhibit?
acetyl-CoA carboxylase
If there is a lot of acetyl-CoA present, what happens to the concentration of citric acid
Increases
What do high concentrations of citric acid stimulate?
Acetyl-CoA carboxylase
When is palmitoyl-CoA present?
In high concentration when fatty acids are in excess
What does the synthesis of triglycerides require?
Glycerol-3-phosphate
What does the liver produce Glycwerol-3-phosphate from?
Glycerol
What does adipose tissue produce G-3-P from?
Glucose
What stimulates adipose tissue uptake of glucose
Insulin
What formation involves esterification?
Triglyceride fromation
Where can all amino acids be completely oxidised?
In the TCA cycle
What happens when amino acids cannot be used for protein synthesis?
Degraded, ocurs mostly in liver
What do proteolytic enzymes in the stomach and intestine produce?
Single amino acids and di and tri-peptides
What initially digests protein?
Proteolytic enzymes in stomach and small intestine
Once proteolytic enzymes have made single amino acids or di, tri peptides, what happens to the peptides?
Absorbed into small intestine
What is anotehr source, other than diet, for amino acids?
Protein turnover
What structures are amino acids?
Tetrahedral structures
What does the breakdown of amino acids create, which needs to be removed?
Nitrogen
What two things does amino acid breakdown produce?
- Ammonia (NH3)
2. Ammonium ions (NH4+)
What ions, produced from amino acid breakdown, are toxic at high concentrations and a build-up leads to severe problems?
Ammonium ions
What is the main molecule used for excreting excess nitrogen?
Urea
How is ammonium ion secreted?
In urine
Where is urea fromed?
In LIVER
Other than urea, what are the other three major nitrogen containing excretory molecules?
Uric acid
Creatinine
Ammonium ion (NH4+)
What happens in the first step of urea synthesis?
Amino group of an amino acid is transferred onto a keto acid (occurs in all tissues)
What is the keto-acid that normally recieves an amino group from an amino acid in urea synthesis?
Alpha-keto-gluterate
What is the step called when amino group of an amino acid is transferred onto a keto acid?
Transamination
If keto-glutarate is the keto acid taking part in the transamination reaction, what is the product?
Glutamic acid
What is the second step of the syhtesis of urea, and where does it occur?
Occurs in liver
Removal of amino group from glutamic acid
What is the removal of an amino group from glutamic acid called?
De-amination
What does the removal of amino group from glutamic acid result in formation of?
Alpha-keto-glutamate
During the second step of urea synthesis, what happens to the extra ammonium ion produced in de-amination?
Enters a cycle of reactions called urea cycle
What is the ornithine cycle?
Urea cycle
What is this step: aminotransferases move the amino group from alpha-amino acids to alpha-keto acids. Usually alpha-keto-glutarate, gives glutamate, occurs in all tissues?
Transamination
In transamination, for transport to the liver what is the amino group of glutamate transferred to?
Pyruvate, giving alanine
In the transport to the liver of transamination, whay is the alternate of amino group of glutamate being transferred to pyruvate making alanine?|
Glutamine synthase adds ammonium ion to glutamate giving glutamine
What are two major carriers of nitrogen in blood to liver?
Alanine and Glutamine
Where does the urea cycle occur?
In the liver
In deamination, what is the amino group of glutamate converted to?
Free ammonium ion
In urea cycle, one nitrogen comes from free ammonium, where does the other come from?
Aspartic acid
In the urea cycle, where does the carbon come from?
CO2
What are the three components that are converted to urea in the urea cycle?
Ammonium ion
Carbon dioxide
Aspartic acid
In teh urea cycle what are 3ATP cleaved to form?
2ADP and 1 AMP
In urea cycle, how many high energy phosphate bonds are broken?
4
What are the two products of the urea cycle?
Fumuerate
Urea
What are carbon skeletons?
The remainder when amino groups have been removed from amino acids
What are remaining carbon skeletonds converted to?
Intermediate metabolites that can be oxidised in TCA cycle
Give three heritable disorders which can derive from probelms with amino acid degradation?
- Alcaptonuria
- Maple syrup urne disease
- Phenylketonuria
What is: a disease which results from blockage of the breakdown of phenylalanine and tyrosine. If these two amino acids cannot be broken down alcaptonuria arises
Alcaptonuria
What is: derived from a block of degradation of valine, isoleucine and leucine. If it is not treated it can lead to severe mental and physical retardation, prevented by appropriate diet.
Maply syrup disease
Whta results from blockage of the breakdown of phenylalanine. If it cannot be broken down it accumulates in all bodily fluids and leads to severe mental retardation if untreated.Therapy involves low phenylalanine diet?
Phenylketonuria
Sometimes enzymes in urea cycle become defective and lead to disease, what do these disorders result from?
Accumulation of intermediates of urea cycle
What increases in urea cycle disorders?
Glutamine levels
If the urea cycle is blocked, what becomes low?
Alpha-keto-glutarate levels
If alpha-keto-glutarate levels become low and lead to build-up of free ammonium ions, what can that be?
Toxic
Give two ways to treat a defective urea cycle?
- Low protein diet
2. Drugs which remove nitrogen/gene therapy in hepatocytes
