5. Liver: Biosynthetic Functions Flashcards
What are the functions of the liver?
Metabolism
Synthesis
Excretion and detoxification: bilirubin, amino acids and NH3, Cholesterol, steroid hormones, drugs, toxins
Name a reaction in the liver that is compartmentalised
Ammonia detoxification
What metabolism is carried out in the liver?
glycogenesis, glycogenolysis, gluconeogenesis and fatty acid metabolism
What substances are made by the liver?
plasma proteins, coagulation factors, haem, lipoproteins, bile acids
What substances are excreted and detoxified by the liver?
bilirubin, amino acids and NH3, Cholesterol, steroid hormones, drugs, toxins
What determines the rate of production of albumin?
Physiological stress
Concentration of colloids in hepatic interstitium
What are the functions of albumin?
Transportation of substances
Oncotic pressure
Describe the production of albumin
- Preproalbumin has a 24 AA extension at the N terminal end
- AA extension signals insertion into ER membrane
- 18 AAs cleaved in lumen=proalbumin
- Proalbumin moved to glogi apparatus, 6AA removed
- Albumin secreted immediately
What conditions can increase albumin loss from plasma?
Nephrosis
Lymphoedema
Where in the body can albumin be stored?
Vascular compartments of skin, muscle, liver, gut
What is the structure of alpha and beta globulins?
Glycoproteins
What are alpha and beta globulins cleared by?
Asialoglycoprotein receptors on surface of hepatocytes
What are the functions of alpha and beta globulins?
Transport
Protease inhibitors
Clotting factors
What might decreased alpha and beta globulins indicate?
Genetic disorder
Malnutrition
What might increased alpha and beta globulins indicate?
Post-inflammation or trauma
What is the structure of haem?
Ferrous iron is chelated onto a porphyrin ring
Name 4 examples of haemoproteins
Haemoglobin
Myoglobin
Cytochrome P450 proteins
Catalase
What is the first enzyme involved in haem synthesis?
ALA synthase
Where is ALA synthase found?
Mitochondria
What is ALA synthase inhibited by?
Non-protein bound haem by negative feedback
Where is ALA dehydratase found?
Cytoplasm
What is the function of ALA dehydratase?
Converts 2 ALA molecules to PBG
Which enzyme is sensitive to inhibition by lead?
ALA dehydratase
What is the function of Uropophyrinogen synthase 1?
Converts 4 PBG to uroporphyrinogen
What are the porphyrias?
Group of metabolic disorders caused by partial defects in one of the haem biosynthetic enzymes
What is Acute Intermittent Porphyria a defect in?
Uroporphyrinogen synthase 1
What does Acute Intermittent Porphyria result in?
Accumulation of ALA and PBG
What is the treatment for AIP?
Haematin respresses ALA synthase
Switches off pathway
What are the features of Porphyria Cutanea Tarda?
Itching, erythema, blistering
What is the cause of PCT?
Deficiency of uroporphyrinogen decarboxylase
What are the consequences of PCT?
Accumulation of porphyrins and porphyrinogens
