Metabolism

Question 1

What two hormones is the liver sensitive to?

Answer 1

Insulin and glucagon

Question 2

What does the liver do in the fed state?

Answer 2

Takes up glucose

Metabolises glucose via glycolysis

Metabolises glucose via the hexose monophosphate pathway

replenishes glycogen stores by glycogenesis/glycogen synthesis

Converts excess glucose to fats by fatty acid synthesis

Question 3

What does the liver do in the fasting state?

Answer 3

Creates new glucose via gluconeogenesis

Converts glycerol to glucose

Converts fatty acids to ketone bodies

Question 4

What are chylomicrons, what do they do in the body? (the process)

Answer 4

Dietary cholesterol and triglycerides are packaged into them in the intestines

they are then broken down by lipoprotein lipase in the capillaries of muscle and adipose tissue to fatty acids which enter cells

Chylomicron remnants are taken up by the liver for disposal

Question 5

What are VLDLs and what do they do in the body? (the process)

Answer 5

The liver synthesises triglycerides and cholesterol and packages then as VLDLs

Reach muscle and adipose tissue then hydrolysed by LPL to fatty acids (taken up by cells)

Become more dense and turn into LDLs

Most LDL’s taken up by the liver for disposal but some circulate and distribute cholesterol to the rest of the body

Question 6

What are dietary amino acids used for the synthesis of?

What is the excess used for?

Answer 6

Hepatic and serum proteins

Biosynthesis of nitrogen-containing compounds, which use amino acids as precursors

Excess is converted to tracylglycerols or…

Protein synthesis/oxidised for energy

Question 7

During fasting the liver can use amino acids for what?

Answer 7

Gluconeogenesis

Question 8

What is the inter-organ glucose alanine cycle?

Answer 8

Alanine used as a means of transporting amino acids from muscle to the liver

So the muscle can get energy from amino acids and the liver can excrete the excess nitrogen

Question 9

What two enzymes are good markers of liver damage, why do hepatocytes have high levels of them?

Answer 9

AST and ALT, both are alanine transferase enzymes

Question 10

What three ways can amino acids be used to produce energy?

Answer 10

Glucose-alanine cycle

Amino acids catabolised to form intermediates in the citric acid cycle - glucogenic reactions

Amino acids are catabolised to form acetoacetate or one of it’s precursors - ketogenic reactions

Question 11

Two main outcomes of metabolism?

Answer 11

Inactivation of a drug so it no longer has activity

Produce metabolites that are more potent e.g. active form of a prodrug

Question 12

What are the two phases of metabolism?

Answer 12

Phase I: ‘pre-conjugation’

Phase II: ‘conjugation reactions’

Question 13

What reactions mostly happen in phase I of metabolism -(pre-conjugation)?

Answer 13

Oxidation reactions

Question 14

What reactions mostly happen in phase II of metabolism?

Answer 14

Glucuronidation

Question 15

In what are polar and non-polar metabolites eliminated in?

Answer 15

Polar in urine

Non-polar in stool

Question 16

What are essential and non-essential amino acids?

Answer 16

Essential are the amino acids ingested from food only

Non-essential are those amino acids that are synthesised in metabolic processes in cells

Question 17

What enzyme are people affected with albinism affected with? Why does this cause the effects?

Answer 17

Tyrosinase, as tyrosine is used to form quinone which forms melanin

Question 18

Tyrosine forms what neurotransmitters?

Answer 18

Dopamine
Tyroxine
Noradrenaline
Adrenaline

Question 19

What does phosphocreatine degrade to produce?

Answer 19

Creatinine and a phosphate ion

Question 20

What conditions have been shown to be helped by creatine treatment?

Answer 20

muscular dystrophy and idiopathic inflammatory myopathy

Question 21

An enzyme used in heme synthesis?

Answer 21

PBG synthase

Question 22

What are porphyrias? what is the main mechanism of pathogenesis of the conditions?

Answer 22

Genetic diseases resulting in decreased activity in enzymes involved in heme synthesis

The main mechanism is the accumulation of porphyrines (heme precursors)

Question 23

An example of a porphyria? Symptoms?

Answer 23

Porphyria Cutana - Present with blisters and photosensitivities

Question 24

Apart from albumin what other transport proteins do you know?

Answer 24

VLDL and HDL can both be used to transport proteins

Question 25

What is Wilson's disease caused by?

Answer 25

Mutations in ATPase resulting in the incorporation of copper into ceruloplasmin

Question 26

What are acute phase proteins? examples?

Answer 26

Proteins synthesised in the liver in response to trauma C-reactive protein Complement Protease inhibitors Coagulation proteins

Question 27

Some results of liver damage on the blood?

Answer 27

Reduced clotting ability Reduced blood ammonia Increased blood: amino acids, albumin synthesis, blood bilirubin Hypoglycaemia

Question 28

What is the difference in lysosomes and proteosomes?

Answer 28

Lysosomes degrade extracellular proteins using proteases Proteosomes degrade intracellular proteins using ubiquitin to label them which requires ATP

Question 29

What enzymes are required for intracellular proteins to be labelled with ubiquitin?

Answer 29

E2 and E3

Question 30

What conditions have been found to have ubiquitin protein mutations affecting them?

Answer 30

Angelman syndrome - can involve an E3 mutation Parkinsons syndrome - E3

Question 31

Main functions of bile?

Answer 31

To aid fat digestion For the excretion of important waste products

Question 32

What organic molecule are bile acids formed from?

Answer 32

Cholesterol

Question 33

Where is cholesterol synthesised to bile acids?

Answer 33

The liver

Question 34

What is the rate-limiting step in the formation of bile acids, what's the enzyme?

Answer 34

7 α-hydroxylase, adding a hydroxyl group to position 7.

Question 35

What are the different types of bile acids?

Answer 35

Primary/secondary bile acids Conjugated bile acids are bile salts

Question 36

What are primary bile acids conjugated to to form bile salts?

Answer 36

Glycine or Taurine

Question 37

What is progressive familial intra-hepatic cholestasis, symptoms?

Answer 37

Mutation in ABC gene (transports bile acids out of hepatocytes) So bile is not secreted out of hepatocytes Causes: pruritis, jaundice, pale stools

Question 38

What is sitosterolemia?

Answer 38

hyper-absorption and decreased biliary excretion of sterols leading to hypercholesterolaemia

Question 39

What generates secondary bile acids from primary bile acids? What changes?

Answer 39

Bacterial enzymes They hydrolyse the amide link to glycine/taurine and the C7 hydroxyl group

Question 40

Examples of primary bile acids?

Answer 40

Glycocholic acid Taurocholic acid

Question 41

Examples of secondary bile acids?

Answer 41

Glyco-and taurodeoxycholic acids

Question 42

What two enzymes mainly regulate bile secretion?

Answer 42

Cholecystokinin Secretin

Question 43

What does cholecystokinin do? What stimulates it's release?

Answer 43

Stimulates the contraction of the gallbladder and the release of bile into the duodenum Released triggered by fat in the duodenum

Question 44

What does secretin do? What stimulates it's release?

Answer 44

Stimulates biliary duct cells to secrete bicarbonate and water increasing the flow of bile out of the biliary ducts Released in response to acid in the duodenum

Question 45

Main cause of gallstones, the aetiology of this?

Answer 45

Decrease in the amount of bile acid, meaning the ration of bile acids to cholesterol falls and the cholesterol becomes insoluble and crystallises.

Question 46

What can cause a decrease in the amount of bile acids?

Answer 46

Malabsorption of bile acids from the intestine Obstruction of the biliary tract Hepatic dysfunction Excessive cholesterol

Question 47

What is Cholelithiasis and Choledocholithiasis?

Answer 47

Cholelithiasis - gallstones in the gall bladder Choledocholithiasis - gallstones in the common bile duct

Question 48

What is amphipathic? Why is this a useful property for bile acids to have?

Answer 48

Means bile acids are both polar and non-polar, useful as it means they have a detergent action on fat, and it emulsifies.

Question 49

What are micelles?

Answer 49

A structure formed from bile acids and lipids They bump the brush border and some lipids are absorbed into epithelial cells

Question 50

What is the enterohepatic circulation? Why is it significant in hepatotoxic compounds?

Answer 50

The fact that venous blood from the intestines goes straight into the portal vein, and most bile acids and cholesterol are extracted back into the portal vein, and liver Significant as other hepatotoxic compounds can become trapped in this circulation and become extremely hepatotoxic e.g. chloramphenicol

Question 51

How do synthetic resins lower cholesterol?

Answer 51

Synthetic resins bind bile acids and or cholesterol and prevent it from being reabsorbed into the enterohepatic circulation and more have to be synthesised

Question 52

What are bile pigments?

Answer 52

Any colouring material found in bile, derived from porphyrins

Question 53

Why do neonates get jaundice commonly?

Answer 53

The hepatic machinery for conjugation and excretion of bilirubin does not function properly till about 2 weeks old

Question 54

How can you treat neonatal jaundice?

Answer 54

Radiating the infants body with light will convert bilirubin to an isomer more soluble in bile, urine and faeces

Question 55

Three types of jaundice?

Answer 55

Haemolytic jaundice (pre-hepatic): - too much bilirubin is produced Hepatocellular jaundice (intra-hepatic) - Disease induced cell necrosis reduces the livers ability to metabolise (conjugate) and/or excrete bilirubin Obstructive jaundice (post-hepatic) - blockage in the bile duct

Question 56

What do increased alkaline phosphatase levels suggest?

Answer 56

Suggests bile ducts are blocked