Case 5- Lipid and Protein Metabolism

Question 1

How much energy is derived from the different energy sources

Answer 1

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.

Question 2

What happens when we eat proteins

Answer 2

• 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.

Question 3

Non-essential amino acids

Answer 3

They can be synthesised from metabolic intermediates or from the carbon skeleton of essential amino acids.

Question 4

Essential amino acids

Answer 4

Amino acids which we cant synthesise and must be obtained from the diet

Question 5

Amino acid pool

Answer 5

Where amino acids ae stored

Question 6

What can happen to amino acids

Answer 6

• Protein biosynthesis
• Biosynthesis of other nitorgen containing compounds
• Oxidation of energy and excretion of nitrogen atoms

Question 7

Nitrogen balance

Answer 7

The difference between nitrogen intake and excretion, when they are equal you are in nitrogen balance

Question 8

Positive nitrogen balance

Answer 8

Nitrogen intake is more then excretion, occurs during childhood and pregnancy

Question 9

Negative nitrogen balance

Answer 9

Nitrogen intake is less then excretion, this is due to catabolic stress, starvation and deficiency in protein intake.

Question 10

Amino acid catabolism

Answer 10

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.

Question 11

Transamination

Answer 11

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

Question 12

Oxidative deamination

Answer 12

The amino group of glutamate is released forming alpha-ketoglurate and amonia. It is catalysed by glutamate dehydrogenase.

Question 13

End products of amino acid catabolism

Answer 13

Alpha-keto acid and Ammonia

Question 14

Types of alpha keto acid

Answer 14

Glucogenic or Ketogenic. The majority of amino acids are Glucogenic then Glucogenic and ketogenic then just ketogenic

Question 15

Glucogenic amino acids

Answer 15

The carbon skeletons of Glucogenic amino acids are converted into Pyruvate or Krebs cycle intermediates, these can act as substrates for Gluconeogenesis

Question 16

Ketogenic amino acids

Answer 16

The carbon skeletons of ketogenic amino acids are converted into acetoacetate or a precursor of acetoate, acetyl CoA or acetoacetyl CoA

Question 17

The 6 intermediates of Glucogenic and ketogenic amino acids

Answer 17

1) Pyruvate
2) Acety CoA
3) Alpha-ketoglurate
4) Succinyl CoA
5) Fumarate
6) Oxalocetate
They can enter the Krebs cycle

Question 18

What happens to ammonia

Answer 18

It is a product of amino acid catabolism. Ammonia is toxic so it is converted into non-toxic urea in the liver

Question 19

How is ammonia excreted

Answer 19

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

Question 20

Other nitrogen waste products

Answer 20

• Uric acid from purine (adenine, guanine) breakdown
• Free ammonia
• Creatine from creatine phosphate

Question 21

Hyperammonaemia

Answer 21

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.

Question 22

Epinephrine and insulin

Answer 22

Epinephrine inhibits insulin release

Question 23

Glucagon secretion

Answer 23

It is secreted by alpha-cells in the pancreas, stimulated by decreased blood glucose, increased epinephrin and inhibited by insulin.

Question 24

How insulin effects Glucagon

Answer 24

Insulin and Glucagon are counter-regulatory hormones, the effect of one counters the effect of another

Question 25

Processes that occur in a fed state

Answer 25

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

Question 26

Processes that occur in the fasting state

Answer 26

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

Question 27

Storage sites for food

Answer 27

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).

Question 28

What storage sites for food do you break down first

Answer 28

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.

Question 29

Overview of fat

Answer 29

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.

Question 30

Overview of skeletal muscle energy source

Answer 30

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

Question 31

What energy sources does the brain use

Answer 31

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.

Question 32

Energy sources of most tissues

Answer 32

In the absence of Glucose fatty acids and ketones can be used

Question 33

VLDL

Answer 33

transports TAG around the body

Question 34

Ketone bodies

Answer 34

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.

Question 35

How are ketone bodies produced overview

Answer 35

TAG’s get broken down into fatty acids which are converted into Acetyl CoA in the liver. They are then converted into ketone bodies

Question 36

Three types of ketone bodies

Answer 36

3-Hydroxybutyrate (major), Acetoacetate and Acetone (not used).

Question 37

Lipid production- malonyl CoA production

Answer 37

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).

Question 38

ACC (Acetyl CoA carboxylase) regulation

Answer 38

• Activated when insulin levels are high
• Activated by citrate (excess energy)
• Inhibited by fatty acids (end product of FA synthesis)

Question 39

What catalyses the majority of FA synthesis

Answer 39

Fatty acid synthase (FAS)

Question 40

Reducing power for FA synthesis

Answer 40

From NADPH which is produced in the hexose monophosphate pathway

Question 41

FA synthesis reactions

Answer 41

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.

Question 42

Main lipid produced

Answer 42

Palmitate (16C) fatty acid

Question 43

What happens after fatty aids are produced

Answer 43

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.

Question 44

Lipid metabolism

Answer 44

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.

Question 45

Hormone sensitive lipase (HSL)

Answer 45

An intracellular enzyme which is activated by Epinephrine and Norepinephrine from Sympathetic nerve endings. Also activated by Glucagon.

Question 46

The variable lengths of fatty acids

Answer 46

• VLCFA (>22 Carbons)
• LCFA ( 12-22 Carbons)
• MCFA (6>12Carbons)
• SCFA (<6 Carbons)

Question 47

Beta oxidation overview

Answer 47

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

Question 48

Beta-oxidation reactions

Answer 48

• 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.

Question 49

The 4 enzymes involved in beta oxidation

Answer 49

Acyl CoA dehydrogenase
Enoyl CoA dehydrogenase
3 Hydroxyacyl-CoA dehydrogenase
Beta-Ketoacyl-CoA thiolase

Question 50

Different types of Acyl CoA dehydrogenase

Answer 50

They are chain length specific so different forms of the enzyme will catalyse different length carbons

Question 51

How different fatty acids enter the cell

Answer 51

• 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.

Question 52

What happens to proteins in Fed state

Answer 52

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.

Question 53

What happens to proteins in fasting state

Answer 53

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.