Fatty Acids and Amino Acids Flashcards
(34 cards)
AA catabolism fate
after proteins –> AA, treated same way dependent on organisms energy needs, they are either
- recycled into new proteins
- oxidised for energy, via removal of AA group or entry into central metabolism
fates of nitrogen in organisms
Humans and great apes excrete both urea (from amino acids) and uric acid (from purines).
Plants conserve almost all the nitrogen.
Many aquatic vertebrates release ammonia to their environment via passive diffusion or active transport
Many terrestrial vertebrates and sharks excrete nitrogen in the form of urea - less toxic and more soluble
Some animals such as birds and reptiles excrete nitrogen as uric acid - insoluble
removal of AA from ammonia
release of free ammonia is toxic, ammonia is captured by a series of transamination reactions
transamination allow transfer of amine to a common metabolite and generate a transportable AA
catalysed by AA-transferases, uses the pyridoxal phosphate cofactor,
α-ketoglutarate accepts amino groups.
o Transfer of one amine toα-ketoglutarate results in synthesis of glutamate (e.g., transamination).
oTransfer of a second amine results in synthesis of glutamine (e.g., glutamine synthetase).
L-Glutamine acts as a temporary storage of nitrogen - can donate the amino group when needed for amino acid biosynthesis.
glutamate safely transported in blood as glutamine
Ammonia Collected in Glutamate Is Removed by Glutamate Dehydrogenase - xxidative deamination occurs within mitochondrial matrix, can use either NAD+ or NADP+ as electron acceptor. Ammonia is processed into urea for excretion, pathway for ammonia excretion; transdeamination = transamination + oxidative deamination
glucose-alanine cycle
Vigorously working muscles operate nearly anaerobically and rely on glycolysis for energy. Glycolysis yields pyruvate.
If not eliminated, lactic acid will build up (in anaerobic conditions) This pyruvate can also be converted to alanine for transport into the liver.
excess glutamate metabolism
Excess glutamate is metabolized in the mitochondria of hepatocytes - glutamate transported via different processes into mitochondrial matrix, ammonia removed to have alpha-keto-glutamate, ammonia converted into carbamoyl phosphate, and this is the 1st step/reaction/substrate for the urea cycle
urea cycle summary
NH4+ from excess glutamate is converted to carbamoyl phosphate. majority of reactions within the urea cycle occur within the cytosol.
citrullene eventually forms arginine and hydrolysed to urea
urea cycle regulation
carbamoyl phosphate synthase I is activated by N-acetylglutamate which is activated by Arginine (acts as allosteric regulator, converts glutamate into carbamoyl phsophate)
Expression of urea cycle enzymes increases when needed.
o high-protein diet
o starvation, when protein is being broken down for energy
end products of AA degradation
Intermediates of the central metabolic pathway
Some amino acids result in more than one intermediate
Ketogenic AA can be converted to acetyl-CoA –> ketone bodies
glucogenic AA can be converted to glucose
AA classification is essential vs nonessential, or ketogenic vs glucogenic
genetic defects in steps of Phe degradation lead to disease
each AA degradation leads to a disease
relationship between enzyme dis-function and disease.
Inborn errors of metabolism
AA synthesis overview
Source of N is Glu or Gln
Derive from intermediates of:
o glycolysis
o citric acid cycle
o pentose phosphate pathway
Bacteria can synthesize all 20.
Mammals require some in diet (essential aa)
AA precursors (7)
CAC: α-ketoglutarate, oxaloacetate
Glycolysis
o pyruvate, 3-phosphoglycerate, phosphoenolpyruvate
Pentose phosphate pathway
o ribose 5-phosphate, erythrose 4-phosphate
synthetic pathway for each amino acid is quite unique
lipids general
organic molecules characterised by low solubility in water and hydrophobic
main: glycerol/triaglycerol, sphingolipids
lipids function
storage of energy: reduced compounds, hydrophobic nature (good packing)
insulation from environment: low thermal conductivity, high heat capacity (absorb heat), mechanical projection (absorb shocks)
water repellant - due to hydrophobic nature, keeping surface of organism dry
buoyancy control - increased density
membrane structure - main structure of cell membranes
cofactors for enzymes - vitamin K (blood clot formation), coenzyme Q (ATP synth in mitochondria)
signalling molecules - paracrine hormones, steroid hormones, growth factors, vitamins A & D
antioxidants - vitamin E
classification of lipids
two major categories based on the structure and function
- Lipids that contain fatty acids (complex lipids)
- can be further separated into: storage lipids (Eg triacylgylycerol) and membrane lipids - Lipids that do not contain fatty acids: cholesterol, vitamins, pigments, etc.
- Main bond for fatty acids, triacylglycerols: ester linkage
- Triacylglycerol: back bone is glycerol
- Other backbone: sphingosine
fatty acids structure
carboxylic acids with hydrocarbon chains with carbons
- saturated: no double bonds between C in chains
- monounsaturated: 1 double bond between C in alkyl chain
- polyunsaturated: 1+ double bond between C in alkyl chain
The cis double bond restricts rotation and introduces a rigid bend in the hydrocarbon tail. All other bonds in the chain are free to rotate.
FA oxidation
1/3 of our energy needs comes from dietary triacylglycerols, 80% of energy needs of heart and liver are met by FA oxidation
brains use glucose, in emergency use ketones
muscles use sugar/glucose, in starvation FFA
FA storage
fats provide efficient fuel storage (over polysaccharides) carry more energy per C and less water because nonpolar
- glucose and glycogen are for short term energy needs and quick delivery
- fats are for long term (months) energy needs, good storage, slow delivery
FA stored as triglycerides
- saturated fats: solid at room temp
- unsaturated fats: liquid at room temp - more movement between molecules, difficult for them align and form same hydrophobic bonds because tails all different shapes
glycolysis and glycerol - TAGs
Glycerol kinase activates glycerol at the expense of ATP.
Subsequent reactions recover more than enough ATP to cover this cost.
Allows limited anaerobic catabolism of fats
(glycerol can be metabolized into glyceraldehyde 3-phospahte, and can enter glycolytic pathway)
FA transport into mitochondria
TAGs are degraded into FA and glycerol in the cytoplasm of adipocytes. synthesis of FA occur in cytosol, allows regulation of processes and ensure two opposing processed don’t occur at the same time.
- Fatty acids are transported to other tissues for fuel through the blood.
- βoxidation of fatty acids occurs in mitochondria.
- Small (< 12 carbons) fatty acids diffuse freely across mitochondrial membranes.
- Larger fatty acids (most free fatty acids) are transported via acyl-carnitine/carnitine transporter.
FA conversion ot fatty acyl-CoA
Transport of 14C+ fatty acids into the mitochondria requires conversion to fatty Acyl-CoA
Break off 2 phosphates, exergonic, releases lots of energy, allows enzyme to catalyse reaciton where adenosine is cleaved and bound to FFA and FFA is bound to CoA (at S-H bond – sulfur group is bound to carboxyl group of fatty acid = fatty acyl-CoA)
FFA goes into cell, transported from cytosol to mitochondria via carnitine trnasporter. Before this happens, FFA needs to be attached to acyl-CoA. Acyl-CoA = acetyl-CoA minus acetyl group. CoA has FFA attached to it via sulfur group. This form allows transport across the mitochondrial membrane. Adeonisne provides energy for this reaction to occur.
This is the first step of β oxidation – investment stage.
Acyl-Carnitine/Carnitine Transport: FAcyl-CoA + Carnitine —–> FAcyl-Carnitine —>Carnitine + FAcyl-CoA
FA oxidation in mitochondria - 3 stages
1: oxidative conversion of 2xC into acetylCoA via β oxidation, generates NADH and FADH2
- involves oxidation of β carbon to this ester of fatty acyl-CoA
2: oxidation of acetyl-CoA into CO2 via citric acid cycle, generates NADH and FADH2
3: generates NADH and FADH2w via respiratory chain
1 is FA equivalent to glycolysis for CHOs
2&3 exactly same as glycolysis
β oxidation pathway - stage 1 FA oxidation
Each pass removes one acetyl moiety in form of acetylCoA,
performed by a single multi-subunit/multi-functional protein
- hetero-octamer: four a subunits and four β subunits
- allows substrate channeling between enzymes
- associated with inner-mitochondrial membrane
- short chain specific FA mitochondrial enzyme
Enzymes of β oxidation
not done yet
oxidation of unsaturated FA
naturally occurring unsaturated FA contain cis double bonds, and so are not a substate for enoyl-CoA hydratase. two additional enzymes are required, an isomerase converts cis double bonds at carbon 3 to trans double bonds and reductase reduce cis double bonds not at carbon 3.
monounsaturated FA require isomerase, polyunsaturated FA require both enzymes.
