Metabolism Flashcards
What two hormones is the liver sensitive to?
Insulin and glucagon
What does the liver do in the fed state?
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
What does the liver do in the fasting state?
Creates new glucose via gluconeogenesis
Converts glycerol to glucose
Converts fatty acids to ketone bodies
What are chylomicrons, what do they do in the body? (the process)
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
What are VLDLs and what do they do in the body? (the process)
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
What are dietary amino acids used for the synthesis of?
What is the excess used for?
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
During fasting the liver can use amino acids for what?
Gluconeogenesis
What is the inter-organ glucose alanine cycle?
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
What two enzymes are good markers of liver damage, why do hepatocytes have high levels of them?
AST and ALT, both are alanine transferase enzymes
What three ways can amino acids be used to produce energy?
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
Two main outcomes of metabolism?
Inactivation of a drug so it no longer has activity
Produce metabolites that are more potent e.g. active form of a prodrug
What are the two phases of metabolism?
Phase I: ‘pre-conjugation’
Phase II: ‘conjugation reactions’
What reactions mostly happen in phase I of metabolism -(pre-conjugation)?
Oxidation reactions
What reactions mostly happen in phase II of metabolism?
Glucuronidation
In what are polar and non-polar metabolites eliminated in?
Polar in urine
Non-polar in stool
What are essential and non-essential amino acids?
Essential are the amino acids ingested from food only
Non-essential are those amino acids that are synthesised in metabolic processes in cells
What enzyme are people affected with albinism affected with? Why does this cause the effects?
Tyrosinase, as tyrosine is used to form quinone which forms melanin
Tyrosine forms what neurotransmitters?
Dopamine
Tyroxine
Noradrenaline
Adrenaline
What does phosphocreatine degrade to produce?
Creatinine and a phosphate ion
What conditions have been shown to be helped by creatine treatment?
muscular dystrophy and idiopathic inflammatory myopathy
An enzyme used in heme synthesis?
PBG synthase
What are porphyrias? what is the main mechanism of pathogenesis of the conditions?
Genetic diseases resulting in decreased activity in enzymes involved in heme synthesis
The main mechanism is the accumulation of porphyrines (heme precursors)
An example of a porphyria? Symptoms?
Porphyria Cutana - Present with blisters and photosensitivities
Apart from albumin what other transport proteins do you know?
VLDL and HDL can both be used to transport proteins
What is Wilson’s disease caused by?
Mutations in ATPase resulting in the incorporation of copper into ceruloplasmin
What are acute phase proteins? examples?
Proteins synthesised in the liver in response to trauma
C-reactive protein
Complement
Protease inhibitors
Coagulation proteins
Some results of liver damage on the blood?
Reduced clotting ability
Reduced blood ammonia
Increased blood: amino acids, albumin synthesis, blood bilirubin
Hypoglycaemia
What is the difference in lysosomes and proteosomes?
Lysosomes degrade extracellular proteins using proteases
Proteosomes degrade intracellular proteins using ubiquitin to label them which requires ATP
What enzymes are required for intracellular proteins to be labelled with ubiquitin?
E2 and E3
What conditions have been found to have ubiquitin protein mutations affecting them?
Angelman syndrome - can involve an E3 mutation
Parkinsons syndrome - E3
Main functions of bile?
To aid fat digestion
For the excretion of important waste products
What organic molecule are bile acids formed from?
Cholesterol
Where is cholesterol synthesised to bile acids?
The liver
What is the rate-limiting step in the formation of bile acids, what’s the enzyme?
7 α-hydroxylase, adding a hydroxyl group to position 7.
What are the different types of bile acids?
Primary/secondary bile acids
Conjugated bile acids are bile salts
What are primary bile acids conjugated to to form bile salts?
Glycine or Taurine
What is progressive familial intra-hepatic cholestasis, symptoms?
Mutation in ABC gene (transports bile acids out of hepatocytes)
So bile is not secreted out of hepatocytes
Causes: pruritis, jaundice, pale stools
What is sitosterolemia?
hyper-absorption and decreased biliary excretion of sterols leading to hypercholesterolaemia
What generates secondary bile acids from primary bile acids?
What changes?
Bacterial enzymes
They hydrolyse the amide link to glycine/taurine and the C7 hydroxyl group
Examples of primary bile acids?
Glycocholic acid
Taurocholic acid
Examples of secondary bile acids?
Glyco-and taurodeoxycholic acids
What two enzymes mainly regulate bile secretion?
Cholecystokinin
Secretin
What does cholecystokinin do? What stimulates it’s release?
Stimulates the contraction of the gallbladder and the release of bile into the duodenum
Released triggered by fat in the duodenum
What does secretin do? What stimulates it’s release?
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
Main cause of gallstones, the aetiology of this?
Decrease in the amount of bile acid, meaning the ration of bile acids to cholesterol falls and the cholesterol becomes insoluble and crystallises.
What can cause a decrease in the amount of bile acids?
Malabsorption of bile acids from the intestine
Obstruction of the biliary tract
Hepatic dysfunction
Excessive cholesterol
What is Cholelithiasis and Choledocholithiasis?
Cholelithiasis - gallstones in the gall bladder
Choledocholithiasis - gallstones in the common bile duct
What is amphipathic? Why is this a useful property for bile acids to have?
Means bile acids are both polar and non-polar, useful as it means they have a detergent action on fat, and it emulsifies.
What are micelles?
A structure formed from bile acids and lipids
They bump the brush border and some lipids are absorbed into epithelial cells
What is the enterohepatic circulation? Why is it significant in hepatotoxic compounds?
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
How do synthetic resins lower cholesterol?
Synthetic resins bind bile acids and or cholesterol and prevent it from being reabsorbed into the enterohepatic circulation and more have to be synthesised
What are bile pigments?
Any colouring material found in bile, derived from porphyrins
Why do neonates get jaundice commonly?
The hepatic machinery for conjugation and excretion of bilirubin does not function properly till about 2 weeks old
How can you treat neonatal jaundice?
Radiating the infants body with light will convert bilirubin to an isomer more soluble in bile, urine and faeces
Three types of jaundice?
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
What do increased alkaline phosphatase levels suggest?
Suggests bile ducts are blocked
