Metabolic Functions Of The Liver Flashcards
Where is glucose stored and what is it stored as?
Liver
Glycogen
What is the conversion of glucose to glycogen stimulated by?
Insulin
Why would glycogen need to be degraded to glucose?
Exercise (skeletal muscle stores)
Fasting (liver stores)
Summarise glycogenolysis
Glycogen -> glucose
Describe the process of glycogenolysis
- One residue of glycogen is removed and converted → glucose-1-P by glycogen phosphorylase
- Glucose-1-P → Glucose-6-p by phosphoglucomutase
- Glucose-6-P → Glucose by glucose-6-phosphatase
- This glucose enters the bloodstream
Summarise glyconeogenesis
Amino acids / lactate / pyruvate / glycerol → glucose
What is gluconeogensis stimulated and inhibited by?
Stimulated - cortisol & glucagon
Inhibited - insulin
Summarise lipogenesis
Acetyl-CoA → Fatty acids
Where does lipogenesis take place?
cytoplasm of hepatocytes
What does lipogenesis require?
ATP
NADPH
What is lipogensis stimulated and inhibited by?
Stimulated - glucagon
Inhibited - adrenaline
Describe the process of lipogenesis
- Acetyl-CoA → Malonyl-CoA by acetyl carboxylase*
- Fatty acid synthase adds malonyl-CoA to a growing fatty acid
- Fatty acid linked to carrier protein
Describe the regulation of lipogenesis
Activated by citrate
Inhibited by AMP
Summarise lipolysis
Fatty acid → Acetyl-CoA
When does lipolysis occur?
Fasting / stress
By what process does lipolysis occur?
β-oxidation
What happens to the Acetyl-CoA after lipolysis?
Enters TCA cycle
or
Used to produce ketone bodies
What is lipolysis stimulated and inhibited by?
Stimulated - glucagon & adrenaline
Inhibited - insulin
Describe the process of lipolysis
- Long chains of fatty acids broken down → series of 2-carbon acetate units
- Acetate units combined with co-enzyme A → Acetyl-CoA
- Acetyl-CoA can be combined with oxaloacetate → citrate for the beginning of TCA cycle
Summarise protein synthesis
Amino acids → Protein
What is protein synthesis stimulated by?
Insulin and GH
Which proteins are synthesised in the liver?
Albumin
Blood clotting factors
Angiotensinogen
Which blood clotting factors produced in the liver are Vitamin K dependent?
2, 7, 9, 10
Summarise transamination
Amino group of amino acids transferred to ketoacids
Describe the process of transamination
Either:
- Amino group added to alpha-ketoglutarate → glutamate by aminotransferase
or
- Amino group added to oxaloacetate → aspartate by aspartate aminotransferase
Summarise deamination
Amino group removed → ketoacid + ammonia
Describe the process of deamination
- Amino group removed from amino acid → ketoacid + ammonia by glutaminase
- Ammonia → ammonium ion
- Must be removed due to toxicity by:
- glutamine
- urea cycle
- Must be removed due to toxicity by:
Why is ammonia toxic to cells:
- Reduces TCA cycle activity
- Affects neurotransmitter synthesis
- Creates an alkaline pH
Describe the process of detoxification of ammonia
- Ammonia is used to synthesise glutamine when combined with glutamate
- Glutamine is used to synthesise nitrogen compounds
- Ammonia transported to kidney:
- Directly excreted
- Transported to liver to make urea
what is the enzyme involved in lipolysis?
triglyceride lipase
what happens to the products of lipolysis?
- fatty acids -> mitochondria for beta-oxidation
- glycerol -> hepatocytes -> glycerol-3-phosphate -> glycolysis
describe the process of ketogenesis
2-Acetyl-CoA
Acetoacetyl CoA (+ Acetyl-CoA) - thiolase
HMG-CoA - HMG-CoA synthase
Acetoacetate (+ Acetyl-CoA) - HMG-CoA lyase
beta-hydroxybutyrate + Acetone
how does Acyl-CoA enter the mitochondria for beta-oxidation?
<12 carbons: diffusion
>12 carbons: carnitine shuffle
what is the purpose of ketogenesis?
uses excess acetyl-CoA
exceeding capacity of Krebs’ cycle
what is ketogenesis activated by?
- low G-3-P
- low ATP demands
- high glucagon
what is ketogenesis inhibited by?
high insulin
why do heart and skeletal muscle preferentially utilise ketone bodies for energy?
preserve glucose for the brain
what is ketosis?
build-up of ketone bodies in the blood
what can cause ketosis?
- diabetic ketoacidosis
- alcoholic ketoacidosis
- starvation
describe the pathophysiology of diabetic ketoacidosis
- lack of insulin -> glucose not taken up by cells -> cannot be used for glucogenesis/glycolysis
- beta-oxidation stimulated for energy
- high acetyl-coA -> ketones -> ketosis -> acidosis
what are symptoms of ketoacidosis?
- hyperventilation
- vomiting
how does ketoacidosis affect the blood?
- excessive ketones lower pH of blood
- impairs ability of haemoglobin to bind oxygen
