Case 5- Lipid and Protein Metabolism Flashcards
How much energy is derived from the different energy sources
Carbohydrates account for 45-65% of energy, fat 20-35% and proteins 10-35% of ypur calorific energy needs. Carbohydrates and proteins generate 4kcal/g whilst fat generates 9 kcal/g.
What happens when we eat proteins
- When we digest the dietary proteins they are split up into amino acids
- They travel in the blood, when they enter cells they generate proteins and other nitrogen containing compounds.
- If there is excess amino acids they are processed and the amine group is removed to form the carbon skeleton which is metabolised to generate energy. The amine group will form urea and will be excreted as urine.
Non-essential amino acids
They can be synthesised from metabolic intermediates or from the carbon skeleton of essential amino acids.
Essential amino acids
Amino acids which we cant synthesise and must be obtained from the diet
Amino acid pool
Where amino acids ae stored
What can happen to amino acids
- Protein biosynthesis
- Biosynthesis of other nitorgen containing compounds
- Oxidation of energy and excretion of nitrogen atoms
Nitrogen balance
The difference between nitrogen intake and excretion, when they are equal you are in nitrogen balance
Positive nitrogen balance
Nitrogen intake is more then excretion, occurs during childhood and pregnancy
Negative nitrogen balance
Nitrogen intake is less then excretion, this is due to catabolic stress, starvation and deficiency in protein intake.
Amino acid catabolism
The first step is the removal of the amino group. This occurs through two linked enzymatic tseps: transamination and oxidative deamination. If we have excess amino acids then they will be rapidly catabolised, the main site of amino acid catabolism is in the liver.
Transamination
Occurs in the cytosol and mitochodria of most tissue. The amino group is transferred to alpha-ketoglutarate forming glutamate and alpha-keto-acid. It is catalysed by aminotransferases
Oxidative deamination
The amino group of glutamate is released forming alpha-ketoglurate and amonia. It is catalysed by glutamate dehydrogenase.
End products of amino acid catabolism
Alpha-keto acid and Ammonia
Types of alpha keto acid
Glucogenic or Ketogenic. The majority of amino acids are Glucogenic then Glucogenic and ketogenic then just ketogenic
Glucogenic amino acids
The carbon skeletons of Glucogenic amino acids are converted into Pyruvate or Krebs cycle intermediates, these can act as substrates for Gluconeogenesis
Ketogenic amino acids
The carbon skeletons of ketogenic amino acids are converted into acetoacetate or a precursor of acetoate, acetyl CoA or acetoacetyl CoA
The 6 intermediates of Glucogenic and ketogenic amino acids
1) Pyruvate
2) Acety CoA
3) Alpha-ketoglurate
4) Succinyl CoA
5) Fumarate
6) Oxalocetate
They can enter the Krebs cycle
What happens to ammonia
It is a product of amino acid catabolism. Ammonia is toxic so it is converted into non-toxic urea in the liver
How is ammonia excreted
In most tissues NH3 combines with glutamate to form glutamine, this is catalysed by glutamine synthetase. In skeletal muscles NH3 combines with Pyruvate to form the glucogenic precursor alanine. Alanine and Glutamine are transported to the liver, ammonia is cleaved of and converted to urea in the urea cycle
Other nitrogen waste products
- Uric acid from purine (adenine, guanine) breakdown
- Free ammonia
- Creatine from creatine phosphate
Hyperammonaemia
Excess in ammonia production caused by defects in liver function or genetic defects in the urea cycle. As ammonia is a neurotoxin its excess can lead to CNS related symptoms like coma, tremors, slurring and drowsiness. The main causes of this are viral hepatitis, acute excessive alcohol abuse and cirrhosis.
Epinephrine and insulin
Epinephrine inhibits insulin release
Glucagon secretion
It is secreted by alpha-cells in the pancreas, stimulated by decreased blood glucose, increased epinephrin and inhibited by insulin.
How insulin effects Glucagon
Insulin and Glucagon are counter-regulatory hormones, the effect of one counters the effect of another
Processes that occur in a fed state
High blood glucose, insulin production, Glycogenesis, protein production, cellular glucose uptake, TAG production. They promote these processes and inhibit the ones in the fasting state. Processes are controlled by Insulin
Processes that occur in the fasting state
Low blood Glucose, Glucagon production, Glycogenolysis, Glucogenesis, protein breakdown, ketogenesis, TAG breakdown. They promote these processes and inhibit the ones done in the fed state. Processes are controlled by Glucagon
Storage sites for food
When dietary intake is surplus to immediate energy requirements. The main energy stores are fat (15kg), protein- skeletal muscle (6 KG) and liver glycogen (0.1kg).
What storage sites for food do you break down first
In fasting stage you use liver glycogen then protein but quickly switch over to fat. The liver glycogen helps maintain blood glucose levels and only lasts for ten hours after a meal. The fat lasts for 3 months.
Overview of fat
Stored as triacylglycerides (TAG) sometimes called tryglycerides and is stored mainly in adipose tissue. During a fast TAG is broken down into Glycerol and fatty acids, Glycerol can be used to make glucose via gluconeogenesis. Fatty acids can be oxidised for energy or converted to ketone bodies in the liver which can be used as an alternative to Glucose.
Overview of skeletal muscle energy source
They are rapidly broken down into amino acids during the initial fasting period, it a slow breakdown after this as it can lead to malfunction of vital organs
What energy sources does the brain use
After a meal the brain uses Glucose, it is the preferred energy source. After 5-6 weeks you get the Glucose from gluconeogenesis but mostly from 3-hydroxy-butyrate and Acetoacetate which are ketone bodies from fat breakdown. Amino acids from the breakdown of proteins can also be used. The 3-Hydroxybutyrate is the major ketone body. The brain can not function without some form of Glucose.
Energy sources of most tissues
In the absence of Glucose fatty acids and ketones can be used
VLDL
transports TAG around the body
Ketone bodies
They are an alternative fuel source to Glucose when Glucose levels are low. They can be used by the brain, skeletal and cardiac muscles, important during a prolonged fast. They reduce reliance on Glucose.
How are ketone bodies produced overview
TAG’s get broken down into fatty acids which are converted into Acetyl CoA in the liver. They are then converted into ketone bodies
Three types of ketone bodies
3-Hydroxybutyrate (major), Acetoacetate and Acetone (not used).
Lipid production- malonyl CoA production
Fats are made from excess acetyl CoA from excess carbohydrate catabolism. Produced in the liver. Excess Acetyl CoA (2 carbons) from the mitochondria is exported to the cytoplasm and carboxylated to malonyl CoA (3 carbons) by Acetyl CoA carboxylase (ACC).
ACC (Acetyl CoA carboxylase) regulation
- Activated when insulin levels are high
- Activated by citrate (excess energy)
- Inhibited by fatty acids (end product of FA synthesis)
What catalyses the majority of FA synthesis
Fatty acid synthase (FAS)
Reducing power for FA synthesis
From NADPH which is produced in the hexose monophosphate pathway
FA synthesis reactions
1) Malonyl CoA is made from excess Acetyl CoA by Acetyl CoA carboxylase (ACC).
2) The excess Acetyl CoA reacts with Malonyl CoA using the fatty acid synthase enzyme and 2NADPH molecules. This will form a 4 carbon compound.
3) The 4 carbon compound will react with Malonyl CoA using the enzyme fatty acid synthase and two NADPH molecules to form a 6 carbon molecule
4) The reaction repeats until you get a 16 carbon molecule.
Main lipid produced
Palmitate (16C) fatty acid
What happens after fatty aids are produced
Three newly synthesised fatty acid molecules are combined with Glycerol to form triacylglycerol (TAG). Liver TAG’S are packed into VDL’s and exported to adipocytes. TAG’s are insoluble and can be packed into a small space meaning they have high energy density.
Lipid metabolism
Adipocyte Triacylglyerides will be hydrolysed into fatty acids and glycerol, this is performed by hormone sensitive lipase (HSL). The Glycerol will be transported to the Liver for Gluconeogenesis. When the FA’s are released they will bind to plasma albumin and will be transported in the blood and enter cells.
Hormone sensitive lipase (HSL)
An intracellular enzyme which is activated by Epinephrine and Norepinephrine from Sympathetic nerve endings. Also activated by Glucagon.
The variable lengths of fatty acids
- VLCFA (>22 Carbons)
- LCFA ( 12-22 Carbons)
- MCFA (6>12Carbons)
- SCFA (<6 Carbons)
Beta oxidation overview
The fatty acids undergo beta-oxidation to form fuel, occurs in the mitochondrial matrix. They will turn into Acetyl CoA which will enter the krebs cycle leading to ATP production. It can also undergo ketogenesis or Gluconeogenesis. Beta oxidation does not occur in the brain
Beta-oxidation reactions
- Fatty acids enter the cell and an acetyl CoA group is added to them to form fatty acid Acetyl CoA derivatives.
- Each cycle has 4 reactions catalysed by 4 enzymes
- Each cycle leaves the Fatty Acyl CoA 2 carbons shorter. These 2 carbons will be removed from the end of Fatty acyl CoA producing Acetyl CoA. This acetyl CoA can enter the Krebs cycle.
- Each cycle will produce an FADH and NADH molecule.
- The cycle repeats reducing the fatty acid by two carbons each time. The reaction ends with the production of two acetyl CoA molecules.
The 4 enzymes involved in beta oxidation
Acyl CoA dehydrogenase
Enoyl CoA dehydrogenase
3 Hydroxyacyl-CoA dehydrogenase
Beta-Ketoacyl-CoA thiolase
Different types of Acyl CoA dehydrogenase
They are chain length specific so different forms of the enzyme will catalyse different length carbons
How different fatty acids enter the cell
- Long chain fatty acids (LCFA) cant directly enter the Mitochondria of cells and enter the Mitochondria matrix via the Carnitine shuttle.
- Medium chain fatty acids (MCFA) and short chain fatty acids (SCFA) can directly diffuse through the mitochondrial membrane and into the matrix.
- Very long chain fatty acids (VCLFAs) cannot be transported into the mitochondria and are initially degraded in the peroxisome into shorter FAs.
What happens to proteins in Fed state
The amino acids are taking up by the tissues, in the skeletal muscle they are converted into proteins. In the liver excess amino acids can be converted into Pyruvate which can be converted into Glucose and Glycogen. In the Liver they are also catabolised into Acetyl CoA then TAG’s and transported to VLDL which can be transported.
What happens to proteins in fasting state
In skeletal muscles the proteins are broken down into amino acids which catabolised into Pyruvate and acetyl CoA in the Liver. In the Liver the Ketone bodies and Glucose can be produced from these products.
