Liver Metabolic functions

Question 1

State the funcions of Zone 1 of the acinus

Answer 1

• Citric acid cycle
• Fatty oxid oxidation
• Gluconogenesis
• Urea synthesis
• Prduction of bile
• respiratory chain

Question 2

The functions of Zone 2 are a bit of a mixed bag of the others. State the functions carried out in zone 3

Answer 2

• Glycolysis
• Glutamine synthesis
• Xenobiotic (substance foreign to the body) metabolsim

Question 3

Summarise the key carbohydrate metabolism reactions that occur in liver

Answer 3

• Storage of glycogen
• Release of Glycogen (glycogenolysis)
• Breakdown of glucose as an energy substrate (glycolysis, citric acid, synthesis of Fatty acids and TG which can also happen from glucose)
• Gluconeogenesis
• Conversion of fructose and galactose to glucose phosphates

Question 4

The liver is important for maintaining a normal blood glucose concentration. Storage of glycogen allows the liver to remove excess ??????from the blood, store it, and then return it to the blood when ?????? levels fall too low. This is called the ???????? of the liver. In a person with poor, gluocse levels after a rich carb meal may be much higher.

Answer 4

• Glucose
• Glucose
• glucose buffer function

Question 5

Gluconeogenesis in the liver also has a role in maintaining a normal ?????? concentration, since it only occurs to a great degree when ?????? levels fall. Large amounts of ?????? and ????? from triglycerides are then convereted into ??????.

Answer 5

glucose

glucose

Amino acids

Glycerol

glucose

Question 6

Although fat metabolism occurs in any cell, certain aspects only occur in the liver. Give examples of such things

Answer 6

• Oxidatiion of fatty acids for energy
  
  • mitochondrial beta oxidation of short chain fatty acids - seems to happen especially quickly in the liver
  • Beta oxidation of fatty acids results in the productin of Acetyl CoA
  • liver cannot use of the Acetyl CoA formed, so is converted to Acetoacetic acid which diffuses into circulation and absorbed into other tissues - where it can again be broken back down into Acetyl CoA and the be oxidsed in the usual manner
• Synthesis of cholesterol, phospholipids and most lipoproteins, fatty acids and triglycerides.
• Synthesis of fat from proteins and carbohydrates

Question 7

Nice lil bonus summary of liver metabolism

Question 8

Outline the major functions of the liver with regards to protein metabolism

Answer 8

• synthesis of plasma proteins (90% of plasma proteins are formed by liver) - Albumin, glycoproteins
• Glycation of amino acids
• Deamination of amino acids to form ammonoia (deamination can occur in the other tissues of the body especially in kidneys but much less)
• generation of urea from ammonia as a result of amino acid breakdown
  
  • Ammonia is also formed as a result of bacteria in the gut, so it is obviously aimed at removal of this as well
  • Ammonia buildup is very dangerous
• Also has a role in synthesis of non-essnetial amino acids

Question 9

Liver has key role in biotransformation and excretion. This is usually for detoxification but can generate toxic or carcinogenic metabolites. Pjhase 1 reactions in the smooth ER mediated by cytochrome ????? produce ?????? or?????? compounds.

Phase 2 reactions include conjugation with glucaronic acid, acetly or methyl radicals, or glycine, taurine or sulphate.

Answer 9

p450

Carboxylated or hydroxylated

Phase 2 reactions include conjugation with glucaronic acid, acetly or methyl radicals, or glycine, taurine or sulphate.

Question 10

State the components of bile

Answer 10

• Water
• cholesterol
• phospholipids
• bile pigments (bilirbun)
• Electrolytes
• Bile salts/bile acids

Question 11

State key functions of bile

Answer 11

• Essential for fat absorption
• Method of cholesterol excretion and other wase

Question 12

State the consequences of Haeme, globins andiron from phagocytosed RBCs

Answer 12

Hame - Bilirubin

Globins - broken into amino acids and recycled

Iron - bound by transferineand returned to iron stores in liver or bone marrow

Question 13

State the 2 main fates of Urobilinogen once it has reached the large intestine

Answer 13

• Oxidized to stercobilin and excreted in feces (90%)
• Rest it returned the liver (10%)
  
  • Can either then circulation to kidneys (5%) and be oxidised to form Urobilin
  • Can also be repackaged into bile

Question 14

Once unconjugated bilirubin with albumin flows into the sinusoids, albumin releases it.

???????? picks up the unconjugated bilirubin and presents it to glucaronic acid. In the liver, it becomes conjugated with the help fo UDP-gluuronyl transferase.

Answer 14

Ligandin

Question 15

Give examples of problems that can affect metabolic function of the liver

Answer 15

• congentinal defects of enzymes
• nutritional deficiency/excess of substrate
• Toxic/chemical damage
• Hypoxia

Question 16

Giver examples of inherited diseases that can cause metabolic liver dysfunction

Answer 16

• Glycogen storage disease - caused by deficiency in Glucose-6-phosphatase
• OTC deficiency - causes hyperammonaemia meaning ammonia cannot be properly broken down
• Amino-acidopathy (has resulting the activation of other pathways to breakdown products)

Question 17

There are various consequences of mitochondrial damage - a common result of liver disease. Study theses.

Note - respiratory chain is just the same as electron transport chain.

The mitochondrial permeability transition pore is something which is formed under certain pathologies like stroke.

Note that the mitochondria is the major site of ROS production under normal physiological conditions.

Answer 17

Question 18

Mitochondrial dysfunction can also be a result of inherited conditions. There are various enzymatic deficiencies that can affect:

Answer 18

Fatty acid oxygenation

organic acids

lactate metabolism

oxidative phosphorylation

urea cycle

Question 19

Examples of toxins to the liver

Answer 19

Question 20

State mechanisms of centrilobular necrosis (i.e. zone 3 of the acinus dies)

Answer 20

• Sepsis
• shock induced ischaemia
• congestive heart failure
• toxicity from drugs and poisons

made worse by:

Malnutrition

infection

fasting

exercise

Question 21

State in broad terms, potential manifestations of metabolic disease of the liver

Answer 21

• No structural abnormalities but severe functional disturbance
  
  • Convrsley, you can have hepatocyte injury leading to apoptosis, necrosis, cirrhosis or tumours
• Excessive lipid, glycogen or other products that manifest as hepatomegaly.

Question 22

State the clinical history of metabolic disease involivng the liver

Answer 22

• newborn acute metabolic crisis - mimics sepsis
• Severe vomitng and failire to thrive
• Recurrent episodes of vomiting and encephalopathy with acidosis
• Progressive retardation or seizures with hepatomegaly
• Hepatomegaly with/without jaundice and failure to thrive/grow normally

Question 23

Answer 23

Question 24

Question 26

Glycogen storage and breakdown:

• After meal, glucose is high and this stimulates secretion of insulin by the Beta cells of the pancreas
• insulin promotes uptake of glucose into liver
• This is stored as glycoegn
• Glycogen can be readily mobilised when plasma glucose falls, for example between meals
• Fall in plasma glucose triggers secretion of glucagon, while insulin declines

Question 27

Polcock: Gluconeogenesis

• synthesis of glucose from noncarbohydrate precursors
  
  • ​stimulated during fastng by hormones include growth hormone, glucagon and cortisol
  • primary site is the LIVER , some also takes place in the kidneys
  • before amino acids can be used for gluconeogenesis, they must be deaminated to produce ammoinum iions, which are subsequently metabolised to form urea
  • Once they have been deaminated, the carbon skeletons can be used for gluconeogenesis.
    *

Question 29

Polcock: Lipid metabolism

• under conditions of plenty fatty acids produced by the liver together with those obtained from the diet are esterified and secreted in the blood as VLDL
• In adipose and muscle tissue, the VLDLs are hydrolysed by lipoprotein lipase to release free fatty acids and glycerol.
• Fatty acids are taken up by the tissue, while the glycerol is transported to the liver or kidneys, where it enters the glycoltic pathway