lipids

definition of a lipid

• classes of biological compounds that are generally insoluble in water but soluble in organic solvents (hydrophobic)

biological functions of lipids (some of them)

• storage of energy

• insulation from environments

• protections of organs

• cofactors for enzymes

• signalling molecules

what is a fatty acid

• usually a component of other lipids

• when not a component of other lipids, known as a free fatty acid

• fatty component: the hydrocarbon chain (hydrophobic)

• acid component: the carboxyl group (negatively charged) (hydrophilic portion)

what is a saturated fatty acid

• have no double bonds in the hydrocarbon chain, tight rigid structure

monounsaturated and polyunsaturated fatty acids

• MUFA - single double bond, resulting in a kink

• PUFA - have multiple double bonds

• the more double bonds, the more fluid the fatty acid and the lower the melting point as more space between molecules as more kinks means less tightly packed

classification of lipids

• carbon in carboxyl group is number 1

• nomenclature reflects number and location of double bonds e.g. 18:1(delta9) means 1 double bond at carbon 9

• cis means H atoms are both on the same side of double bond

omega-3 and omega 6 fatty acids

• omega 3 means double bond starts at the third carbon from the last carbon and are considered anti inflammatory

• omega 6 means double bond starts at the 6th carbon from the last carbon and are considered pro inflammatory

what classification is arachidonic acid

• omega 6 polyunsaturated fatty acid

• regulates inflammation and immune response

• structural component of cell membranes

arachidonic acid derivatives

• prostaglandins - controls renal blood flow, inflammation and fever

• thromboxanes - formation of blood clots

• leukotrienes - smooth muscle contraction in lungs

roles and structure of triglycerides

• contains 3 fatty acids and glycerol

• ester bonds link OH groups to carboxyl group of fatty acud

• ester bonds can be hydrolysed by lipases or esterases

• have to be digested because they cant cross cell membranes, then reconverted into triglycerides within cell and exported as chylomicrons into the blood as part of the lipoprotein pathway

role of chylomicrons (triglycerides)

• contain phospholipids and lipoproteins

• chylomicrons enter lymphatic system via lacteals where they join lymph fluid to become chyle fluid

• chyle returns to vascular system through venous return and supplies tissues with triglycerides

what is the lipoprotein pathway

• supplies fatty acids and cholesterol in various tissues

• same components as chylomicrons

• exogenous pathway (dietary fat), dietary fats into chylomicrons, lipoprotein lipase unloads triglycerides into muscle and fat tissue and remaining chylomicron remnants are absorbed by liver

• endogenous pathway (liver fat), packages cholesterol and fats into VLDLs, which are then converted into IDLs which are taken up by liver or converted into LDLs which deliver cholesterol to cells

where are fats stored

• fat tissue (adipose tissue)

what is lipogenesis

• synthesis of fatty acids

• excess glucose is converted into fatty acids for long term storage

• acetyl coA from glycolysis and pyruvate formed

• NADPH is required for each additional acetyl coA as well as glycerol to form triglycerides

• triglycerides exported from liver as VLDLs to other tissues

what is lipolysis

• breakdown of stored triglycerides to fatty acids and glycerol

• induced by hormones (when body in starvation mode)

• free fatty acids and glycerol are transported by the blood to liver, skeletal muscle and cardiac muscle

• the brain cannot utilise fatty acids as they cannot cross the blood brain barrier (use glucose as energy store)

how are fatty acids metabolised

• beta oxidiation

• transported into the mitochondira by the carnitine shuttle

process of the carnitine shuttle

• fatty acid bound to coenzyme A to form fatty acyl CoA which requires fatty acyl CoA synthetase

• CoA exchanged for carnitine to form acyl carnitine using carnitine palmitoyltransferase I (CPT1)

• acyl cartnitine translocated by facilitated diffusion with unbound carnitine using Carnitine acylcarnitine translocase

• carnitine one acyl carnitine exchnaged for coA using CPT2

• used to transport long chain fatty acids into the mtiochondria

beta oxidation

• the breakdown of fatty acids two carbons at a time into acetyl coA, also producing NADH and FADH2 (that can regenrate ATP via ETC)

• acetyl coA can enter krebs cycle

what happens when fatty acids and acetyl coA are in excess?

• acetyl coA enters ketogenesis

what is ketogenesis

• when excess acetyl coA is converted into ketones (acetone, acetoacetate) which can be used by brain and muscles as secondary energy source

• acetone has no metabolic function and is excreted in breath (can be detected in urine and blood)

what are glycerophospholipids

• contain 2 fatty acids (usually one saturated and one unsaturated), glycerol, phosphate (negatively charged) and a polar head group

two main examples of glycerophospholipids

• phosphatidylcholine (most common phospholipid of plasma membrane)

• phosphatidylinositol 4,5 - biphosphate (involved in cell signalling)

what are sphingolipids

• similar to phospholipids but only have one fatty acid which is linked to sphingosine (ceramide = fatty acid + sphingosine)

• consists of phosphocholine head group, sphingosine and a fatty acid

• found in myelin sheath, plays a role in action potential and involved in apoptosis

• blood groups

properties of cholesterol

• high carbon content (hydrophobic)

• ring structure

• needed for steroid hormone synthesis and membrane function

• animals can obtain cholesterol from diet or acetyl coA

what do bile acids do

• regulate cholesterol levels and remove excess cholesterol by breaking it down

• solubilises lipids (makes them water soluble)

• break up fats into smaller droplets or micelles to aid digestion

• bile acids coat lipid droplets

role of vitamin D

• lipid soluble

• aids calcium absorption from small intestine

• multi step process of synthesis involving skin, liver and kidney

lipid soluble vitamins

• A

• D

• E

• K

role of vitamin A (aka retinol)

• hydrophobic

• produced from B carotene

• can be converted into retinoic acid - hormonal signal to epithelial cells

• can be converted into all-trans-retinal - neuronal signal to brain

role of vitamin E

• hydrophobic

• antioxidant properties

• protects fatty acids within cell membranes from oxidation (acts as a cofactor)

role of vitamin K

• hydrophobic

• important cofactor in blood coagulation pathway (regulation of bleeding) (blood clotting cofactor)

• carboxylase adds carboxyl group to glutamate residues in clotting factors which can then gather calcium which enables factors to bind to cell membrane and form clot

• vitamin K is oxidised so must also be reduced

• cause blood clotting

why is vitamin A toxic at high doses but vitamin C is not?

• vitamin C is water soluble so can be easily excreted by kidneys

• vitamin A is hydrophobic so needs to be converted to a more hydrophilic product for excretion

• vitamin A is also stored in adipose tissue which is not accessible to drug metabolism enzymes