Cell metabolism II Flashcards
What are some examples of lipids?
Free fatty acids, triacylgycerolis, phospholipid, glycolipids and steroids
What is the structure of triacylglycerols?
Consists of a molecule of glycerol chemically bonded through a condensation reaction forming ester bonds to 3 fatty acids
Occurs between hydroxyl group of glycerol, and the carboxyl group of the fatty acids.
What are the properties of triglycerides?
Long hydrocarbon tails are hydrophobic, insoluble in water
What are saturated lipids?
Saturated lipids have single carbon bonds, this means that they have reached the maximum amount of hydrogen bonds. Each carbon atom is bonded to the adjacent one with a single covalent bond.
What are the properties of saturated lipids?
Saturated lipids have higher melting points ,being solid at room temperature.
What are unsaturated lipids?
Unsaturated lipids have double carbon bonds, meaning that they have the ability to bond to more hydrogen atoms, through a hydrogenation reaction.
What is the biological significance of triglycerides?
Energy storage molecules Waterproofing Thermal insulation Protection of internal organs Source of metabolic water Buoyancy
Why are triglycerides good energy storage molecules?
Hydrocarbon tail of fatty acids contain a lot of chemical energy, thus a lot of energy is released when oxidised during cellular respiration
store twice as much energy per gram
Why are triglycerides good for waterproofing?
Hydrophobic nature of lipids reduces water loss through evaporation
Why are triglycerides good insulators?
Thick layer reduces SA:V ration, reducing heat loss. Stored within adipose tissue under subcutaneous fat
What is the product of B-oxidation?
Acetyl-CoA molecules
Where does b-oxidation occur?
Mitochondria
What are the sources of fats?
The diet, de novo biosynthesis, and storage deposits in adipose
What is de novo synthesis?
Synthesis of complex molecules from simple molecules.
What are bile salts?
Salts generated by the liver and stored within the gallbladder. Secreted from the bile duct into the intestine emulsifying fats to increase surface area, assisting digestion
What vitamins does bile salts assist in the absorption of?
Vitamin A,D,E & K
What results from a bile salt deficiency?
Fat passing through the gut undigested and unabsorbed resulting in steatorrhea
Describe the mechanism of action of Orlistat?
Potent inhibitor of gastric and pancreatic lipase, behaves as a competitive inhibitor of lipase.
Prevents lipids and reduces fat absorption
What are the benefits or orlistat?
Can be used to treat obesity
What are lipoproteins?
Lipids are transported in the plasma by lipoproteins.
What is the role of chylomicrons?
Dietary fat transport
What is the role of VLDLs?
Endogenous fat transport
What is the role of IDLs?
LDL precursor
What is the source of VLDLs?
Liver
What is the role of LDLs?
Transport of cholesterol
What is the role of HDLs?
Reverse cholesterol transport(Back to liver)
What cells lining the brush border of the small intestine absorb dietary fat?
Enterocytes
What are stored within chylomicrons?
Triglycerides
What do high-density lipoproteins donate to chylomicrons?
Apoproteins
What is the fate of chylomicrons?
Lipoprotein lipases located on endothelial cells enzymatically hydrolyse the triglycerides into fatty acids and glycerol, these enter into adipocytes.
What occurs within adipocytes to fatty acids and glycerol?
Formed into triglycerides and stored within adipocytes
beta oxidation
Hormone sensitive lipase regulates the storage of triglycerides within adipocytes
How are fatty acids transported within the blood?
As albumin
Describe the life cycle of chylomicrons?
Nascent chylomicrons with triglycerides –> HDL transfers apoproteins –> Chylomicrons releases NEFA & glycerol –> Recycled in liver
What forms the monolayer of lipoproteins?
Cholesterol, and phospholipids
Apoproteins
What does the lipoproteins encapsulate?
Cholesterol esters and triacylglycerides
Where does lipoprotein synthesis occur?
Occurs within the liver
What are cholesterol esters formed from?
Formed from cholesterol and the dactyl chain of phosphatidylcholine by lecithin cholesterol acyltransferase
How are cholesterol molecules transported in the blood?
Converted into cholesterol esters, and stored within LDLs
Why is cholesterol converted into cholesterol esters?
Ester linkages remove hydroxyl group, decreasing the water solubility
What is the function of HDLs?
Extracts cholesterol from cell surface membrane, converting them into cholesterol esters via LCAT
reverse cholesterol transport, transports to liver, and reduces total serum cholesterol
What is the initial stage of beta oxidation?
Conjugation with coenzyme A in the cytosol by acyl CoA synthetase forming an acyl-Coa species
What is the function of beta-oxidation?
Reduced hydrogen carriers (NADH, FADH2) used in ATP synthesise by oxidative phosphorylation
Acetyl-CoA used as a substrate in the TCA cycle
How are fatty-acyl-CoA molecules transported into the inner mitochondrial membrane?
Carnitine shuttle, modified by carnitine palmitoyl transferase -1 to acyl carnitine
What cytosolic enzyme converts carnitine into acyl carnitine?
Carnitine acyltransferase-1
What transports acyl carnitine across the inner mitochondrial membrane?
Carnitine translocatie
What is the destination of acyl carnitine within the matrix?
Acyl carnitine is cleated by Carnitine acyltransferase-II into carnitine and acyl-CoA
What is the fate of acyl-CoA?
Acyl-CoA undergoes beta oxidation
What type of disorder is primary carnitine deficiency?
Autosomal recessive disorder
Which gene encodes for carnitine transporter protein?
SLC22A5
What does the mutation in the SLC22A5?
Reduced ability to intake acylcarnitine into matrix for beta oxidation
When does beta-oxidation end?
Until acetyl-CoA forms
Palmitoyl-CoA is a 16 carbon compound, how many acetyl-CoA potentially forms?
8 Acetyl-CoA molecules, 16 carbon compound is consecutively decarboxylated to remove 2 carbons from acyL-CoA, forming acetyl-CoA
How many cycles of beta-oxidation is required to generate 8 acetyl-CoA molecules?
7
What is the fate of acetyl-CoA?
Oxidised in the TCA cycle provided oxaloacetate is present; used for lipogenesis; and the formation of ketone bodies.
What are the products of one cycle of beta oxidation?
1 FADH2, 1NADH, 1 acetyl-CoA
How many molecules of ATP does acetyl-CoA yield?
12 ATP
3NADH = 3 x 3 = 9
FADH2 = 2
1 GTP
How many high energy bonds are utilised in beta oxidation?
2 ATP –> AMP
How many ATP molecules does 16 Carbon fatty acid yield?
129
What occurs during hypoglycaemia?
Ketone body formation,
What does acetyl-CoA form during ketone body formation ?
Acetyl CoA forms acetoacetate, D-hydroxybutyrate and acetone (ketone bodies); ketogenesis occurs in liver mitochondria.
What organs do ketone bodies supply?
Brain, heart, skeletal muscle
What is lipogenesis?
Lipogenesis is the metabolic formation of fat; utilising two enzymes: acetyl CoA carboxylase and fatty acid synthase.
How are fatty acids formed?
Elongation , reduction and dehydration
What protein are developing fatty acyl groups linked to?
Acyl carrier protein
Compare the carriers between lipogenesis and and beta oxidation?
Acyl carrier protein v CoA.
What is the reduction power for lipogenesis?
NADP
What is the reducing power for beta oxidation?
FAD/NAD+
Where does lipogenesis occur within a cell?
Cytoplasm
Where does beta oxidation occur within a cell?
Mitochondrial matrix.
What is MCADD?
Medium chain acyl-CoA dehydrogenase deficiency
What is the pathology of MCADD?
Prevents degradation of triacylglycerols and fatty acids, thus inhibiting B-oxidation, reducing ATP synthesis
What are the recommendations for patients with MCADD?
Adhere to high carbohydrate diet, should not fast longer than 10-12 hours
What are the metabolic features of the brain?
Requires continuous supply of glucose, cannot metabolise fatty acids
Ketone bodies used as a partial substitute
What are the metabolic features of the heart?
Cardiac cycle and cardiac contraction designed for aerobic respiration.
Utilises Krebs cycles substrates
Cell necrosis and death
What is gluconeogenesis?
The biochemical process, in which the respiratory substrate, glucose is synthesised from non-carbohydrate sources (amino-acids, lactate and glycerol)- the process mainly occurs in the liver and the cortex of the kidney; occurs when body carbohydrate levels are insufficiently low. Maintains blood glucose level.
Which precursors enter gluconeogenesis?
Pyruvate, oxaloacetate, dihydroxyacetone phosphate
What is the aim of the gluconeogenic pathway?
Lactate generated by skeletal muscle taken liver, lactate dehydrogenase through Cori cycle produce pyruvate
What amino acids supply gluconeoegenesis?
Glucogenic amino acids
What molecule is used to form dihydroxyacetone?
Glycerol backbone
Which reaction must be bypassed first for gluconeogenesis?
Phosphoenolpyruvate + ADP –> Pyruvate + ATP (Pyruvate kinase)
What is the first step of gluconeogenesis?
Pyruvate carboxylated into oxaloacetate, ATP required
Decarboxylated and phosphorylate to yield phosphoenolpyruvate
What do ketogenic amino acids form?
Undergo ketogenesis to form ketone bodies
Under anaerobic conditions what processes occur?
Cardiac glucose output increases, gluconeogenesis, glycogenolysis
What are isoforms?
Different forms of hexokinase within muscle and liver, maximally active at different concentrations of glucose
What is Michaelis constant (KM)?
Concentration of substrate at which enzyme function at half-maximal rate (Vmax)
What is the Km of hexokinase-1 found in the muscle?
0.1mM active at low concentrations of glucose, operation of maximal velocity
What molecule is hexokinase sensitive to inhibition to?
Glucose-6-phosphate
What happens under anaerobic conditions to hexokinase-1?
Accumulation of glucose-6-phosphate results in inhibition of activity
What comparison of sensitive is hexokinase-1 in muscle compared to hexokinase-4 (liver)?
Higher km, less sensitive to glucose-6-phosphate (glycogen)
What is glucose-6-phosphatase?
Found in liver, catalyses the reverse reaction of hexokinase, generating glucose from glucose-6-phosphate
What is the function of glucagon?
Secreted during hypoglycaemic conditions; stimulates increased glucose cardiac output (glycognenlysis & gluconeogensis)
Which cell secretes glucagon?
Alpha cells of the islets of Langerhans
What effect does adrenaline have of glucose?
Increases rate of glycolysis, gluconeoegenesis and fatty acid release
What 2 enzymes are used in lipogenesis?
Acetyl CoA Carboxylase and Fatty acid synthase
Outline the carnitine shuttle and its purpose
To transport acyl CoA groups into the mitochondria for fatty acid B-oxidation
First step of fatty acid oxidation?
2 high energy bonds used
Fatty acid –> Acyl CoA
What kind of reaction is this?
Group transfer-Transamination
How is acetyl CoA able to easily donate acetate(2C) to other molecules?
The thioester bond is a high-energy linkage, so it is readily hydrolysed.
Why is NAD+ so crucial for ATP generation?
NAD+ you recall, is needed for the dehydrogenation of glyceraldehyde 3-phosphate, which is the first step in generating ATP for the body.
