Lipid Metabolism Flashcards
Types of lipids
- triglycerides (main one)
- phosopholipids
- cholesterol
Fatty acids
Basic moiety of all lipids
- long chain hydrocarbon organic acids
Lipid functions
Triglycerides are used primarily for energy production (similar to CHO)
- composition: 3 fatty acids and 1 glycerol
- cholesterol and phospholipids used to make cell membranes
Lipoproteins
Carrier service for lipids in the plasma
- transport lipids to and from liver
- transport lipids to other tissues for use/storage
- made of cholesterol, triglycerides, phospholipids, and protein
Types of lipoproteins
- chylomicrons: carry digested fat from intestines to lymphatics (most relevant)
- low density lipoproteins: contains higher cholesterol
- very low density lipoproteins: high triglycerides/moderate cholesterol
- high density lipoproteins: contains lower cholesterol
Bile formation
Bile is made by hepatocytes at rate of 1/2 - 1 liter/day
- stored in gallbladder
Functions
- fat digestion
- excretion of wastes, including cholesterol and bilirubin
Bile composition
Bile salts make up 50% of composition
- bile salts made from cholesterol –> cholic acid or chenodeoxycholic acid –> conjugation with taurine or glycine –> conjugated bile acids
Role of bile salts
Bile released from gallbladder when fat reaches duodenum
- contraction stimulated by cholecystokinin
- bile salts emulsify fat globules and then form micelles that allow further digestion/absorption of fats
- bile salts are left behind in GIT lumen and recycled back to liver for repeat use
Cholecystokinin via blood stream causes
- gallbladder contraction
- relaxation of sphincter of Oddi
Where is bile stored?
Gallbladder
- concentrated up to 15 times
What does secretin in the bloodstream do?
Stimulates liver ductal secretion
- Na and HCO3 added via secretin hormone to prevent bile from being too acidic
Step 1 of lipid digestion
Bile salts break down fat globules (mostly TG) into smaller sizes (emulsification) so lipase enzymes can act on them
Step 2 of lipid digestion
Bile salts form micelles
- micelles allow water soluble enzymes to act further on fat for digestion
- shuttle broken down fats (free fatty acids) to the intestinal brush border and release them into the intestinal cells
- free fatty acids shuttled to smooth ER of cell and new TG are packaged into chylomicrons –> released from base of cell into thoracic duct OR FFA are absorbed directly into blood from GIT
What is the biggest component of a chylomicron?
Triglycerides
Chylomicrons
Type of lipoprotein, mostly triglycerides
- increase in serum after a meal, causing turbidiy or whitish color, while they carry TG in the bloodstream
- are cleared within 30 minutes in normal animals
Primary hypertriglyceridemia in dogs
Breed predisposition - schnauzers - shetland sheepdogs Diagnosis - elevated FASTING triglycerides Consequences - pancreatitis - poor glucose regulation in diabetics - ocular problems
Fate of triglycerides in the blood: option 1
Taken up by liver
- TG split into free FA –> oxidation of FA to supply ATP for body functions OR synthesis of cholesterol, phospholipids, and most lipoproteins
_____ of cholesterol made in liver is converted to bile salts
80%
- remainder is transported in lipoproteins in the blood to needy tissues
Phospholipids made in liver
Transported by lipoproteins
- cell membrane formation
- intracellular structure formation/reactions
- second messenger systems
Fate of TG in the blood: option 2
Used by other tissues for energy or storage
- especially adipose, heart, and muscle
- taken up via lipoprotein lipase (LPL) found in walls of capillaries
- chylomicron –> LPL –> TG and phospholipids –> free FA + glycerol (lipolysis)
- left over chylomicron is cholesterol rich and gets cleared by liver
Free FA is used for
- energy via beta oxidation, Kreb’s cycle, and oxidative phosphorylation
- storage of fat
- production of new TG or other lipids
Lipolysis
TG hydrolyzed to FA + glycerol
- glycerol enters cells –> glycolysis
- FA goes to needy tissues –> further processing
Lipolysis step 2
Fatty acids shuttled to mitochondria
- FA moved to mitochondria for degradation and oxidation
- amino acid carnitine acts as an enzyme to assist in this movement
Lipolysis step 3
Beta oxidation of fatty acids yields acetyl CoA
- yields 4 H+
Lipolysis step 4
Acetyl CoA enters TCA cycle
- products (per acetyl CoA): 2 CO2, 8 H+, 1 ATP
Lipolysis step 5
Oxidative phosphorylation of >100 H+ atoms from previous steps
- yields more than >100 ATP
When would the body make more fatty acids?
- if body can’t use carbs (diabetes)
- in starvation
- to store excess carbs and protein
Synthesis of fatty acids from excess carbs and protein
Necessary if CHO or protein are in excess and no more glycogen can be formed
- storage of fat provides a log of energy back up
- fat is more energy dense than carbs
- 1st step is conversion of glucose or AA to acetyl CoA
Synthesis of fat from proteins and CHO occurs in the ____
Liver
Lipid storage
Adipose tissue’s major function is storage of TG until needed by liver or other tissues
- adipocytes are 80-90% stored fat
- TG stored inside cell in liquid form
- lipases are activated once this stored fat is needed by the rest of the body
Tapping into lipid stores
When cells need energy, hormone sensitive lipase can signal release of stored fat from adipose
- stored fat –> hormone sensitive lipase –> free FA in blood –> binds albumin –> tissue in need
Free FA concentration is significantly increased in absence of ____
Carbs or inability to use carbs
- ex: diabetes mellitus
What happens if lipid concentrations are too elevated?
Liver degrades excess fatty acids into keto-acids (ketones)
- FA –> acetyl CoA –> ketones –> cells –> acetyl CoA –> TCA cycle
- FA –> acetyl CoA –> ketones –> ketoacidosis (in a state of no carb metabolism)
Diabetic ketoacidosis
Accumulation of ketones is common in sick or poorly controlled diabetics
- due to insufficient insulin or insulin resistance
- causes illness, acidosis, vomiting/diarrhea, lethargy, inappetence
Hormonal control over lipid metabolism
Insulin-decreased CHO utilization and fat storage, increased fat mobilization (free FA) for energy
- thyroxine-rapid mobilization of fat to release free FA
What activates hormone sensitive lipase and releases free FA for energy
- epinephrine
- glucocorticoids
- growth hormone
What signals satiety to the hypothalamus?
Leptin
- produced by full adipocytes
- released into bloodstream —> hypothalamus
- decreases fat storage
- decreases appetite
Fat soluble vitamins
- A: stored as retinol, needed for retinal development, epithelial health, reproduction
- D: increases calcium and phosphorous absorption from GIT and bone
- E: antioxidant
- K: necessary cofactor for activates (carboxylates) clotting factors 2, 7, 9, and 10
