liver function Flashcards
what are the functions of the liver
- metabolism
- synthesis (plasma proteins, cholesterol, bile acids, urea)
- waste management
- +++
What is the role of the liver in energy metabolism?
- Convert amino acids into energy (glycolysis)
- Store glucose as glycogen
What are the liver enzymes involved in energy metabolism?
- Aspartate aminotransferase (AST)
- Alanine aminotransferase (ALT)
What is the function of aspartate aminotransferase (AST) in energy metabolism in the liver?
Glycolysis
- Role in the malate-asparate shuttle
Aspartate can be converted to malate in a reversible reaction (intermediate = oxaloacetate)
- Malate is produced in the cytoplasm and then converted back to aspartate in the mitochondria
- Malate -> oxaloacetate in the mitochondria produces NADH
- NADH is then used to produce ATP by oxidative phosphorylation
- AST catalyses the conversion between aspartate and oxaloacetate
What is the role of alanine aminotransferase (ALT) in energy metaolism in the liver?
Gluconeogenesis
- Amino acid catabolism
- Alanine reacts with alpha-ketoglutarate to form glutamate and pyruvate (catalyzed by ALT)
- Pyruvate can be used to produce glucose or enter the Kreb’s cycle
How can liver enzymes be used to diagnose liver damage?
AST and ALT are only found in the blood when liver damage is present
list plasma proteins made by the liver
- serum albumin (highly abundant carrier protein that maintains osmotic pressure)
- very low density lipoprotine
- high density lipoprotein
- fibrinogen
- prothrombin
- trasnferrin
- complement proteins
what is important about hypoalbuminemia
albumin synthesized exclusively by hepatocytes BUT
hypoalbuminemia is not specific for liver disease as can be low in cases of malnutrition etc
what do lipoproteins do
move insoluble fat around
- triglycerides
- phospholipids
- cholesterol esters
lipoproteins are linked to which kind of protein
apolipoproteins
what are the functions of apolipoproteins
- activate enzymes
- bind receptors
- stabilise lipoprotein
Describe the synthesis of cholesterol in the liver
- Acetyl-CoA + actetoacetyl-CoA
- Carbon chain lengthens
- Decarboxylation => cholesterol
- Cholesterol can then be converted to bile salts in the liver or moved to endocrine glands to become steroid hormones
How are bile salts formed in the liver?
- Bile acids are cholesterol derivatives
- Cholic acid (main bile acid) conjugates with amino acids to reduce the pK (reduce acidity) of amino acids so they exist in ionised forms as bile salts
what are micelles in the liver
- bile salts in aqueous solution tend to form aggregates or micelles
- amphiphilic (+ve inside, -ve outside)
- bile salts are conjugated with cholesterol and phospholipids
- the -ve external charge prevents them from coalescing
what is the purpose of bile
- acts as a detergent to emulsify fats (increases their surface area by breaking them into small bits)
- emulsification occurs by associating the hydrophobic side with lipids and the hydrophilic side with water. since the bile increases the absorption of fats it is an important part of the absorption of fat soluble vitamins (A, D, E and K)
- phospholipids are hydrolysed by pancreatic phospholipase A2 and cholesterol by esterase
Describe the route of bile acids
- Absorbed in ileum
- travel to liver via hepatic portal vein
conjugate with cholesterol to form conjugated bile acids - travel to gall bladder then into the duodenum where they cause fat absorption
- travel down to ileum and reabsorbed
How is fat absorbed in the small intestine?
- Bile salts and pancreatic lipase break large fat droplets down
- Micelles formed as bile salts form aggregates, conjugated with phospholipids and cholesterol
- Micelles release into epithelial cells/enterocytes
- Free fatty acids and monoglycerides within mycelle diffuse into enterocyte
- Triglycerides resynthesised and chylomicrons formed in enterocyte (chylomicrons are exocytosed into lymph vessel)
Describe the detoxification of foreign chemicals in the liver
2 phases:
phase 1 = relies on cytochrome P450 to modify the chemical
phase 2 = conjugation reactions
how does the liver manage endogenous waste
Bilirubin Metabolism: Converting heme breakdown products to conjugated bilirubin for excretion.
Ammonia Detoxification: Converting ammonia to urea via the urea cycle.
Hormone Metabolism: Inactivating and excreting hormone metabolites.
Detoxification of Metabolic Intermediates: Converting lactate and ketone bodies to usable forms or excreting them.
Handling ROS: Using antioxidants to neutralize reactive oxygen species.
Autophagy: Recycling cellular components through autophagic processes.
Describe the role of the liver in the detoxification of endogenous and exogenous substances. Include specific examples of how the liver processes hormones and drugs.
The liver detoxifies hormones such as insulin and glucagon by breaking them down. It also metabolizes drugs through the cytochrome P450 enzyme system, converting lipophilic substances into more water-soluble forms for excretion.
Explain the process by which the liver converts ammonia to urea. Why is this process important for the body?
The liver converts ammonia to urea via the urea cycle, involving enzymes such as carbamoyl phosphate synthetase. This process is crucial to prevent ammonia toxicity.
Discuss the role of the liver in protein synthesis. Identify at least three types of plasma proteins synthesized by the liver and their functions.
the liver synthesizes albumin (maintains oncotic pressure), clotting factors (e.g., fibrinogen for coagulation), and transport proteins (e.g., transferrin for iron transport).
Explain the processes of deamination and transamination in the liver. How do these processes contribute to amino acid metabolism?
Deamination removes amino groups from amino acids, producing ammonia, while transamination transfers amino groups to form new amino acids. These processes help in amino acid catabolism and synthesis.
Describe the urea cycle and its significance in amino acid metabolism. What are the consequences of urea cycle disorders?
The urea cycle converts toxic ammonia into urea for excretion by the kidneys. Disorders in this cycle can lead to hyperammonemia, causing neurological damage.