Metab 1-6, protein and lipids Flashcards
what is the 1st step in amino acid breakdown?
-NH2 removed by transamination or deamination and converted to urea to be excreted in urine
what happens to the carbon skeleton part of the amino acid that’s left over?
converted into different compounds to feed into other metabolic pathways
what are glucogenic amino acids?
feed into gluconeogenesis pathway to make glucose
what are ketogenic amino acids?
converted to acetyl CoA –> ketone bodies (via synthase to HMG CoA, then then via lyase to acetoacetate –> acetone)
what happens in transamination
-NH2 gets moved from an amino acid to a keto acid
what happens when a-ketoglutarate is the keto acid used? which enzyme is used?
the addition of amino group (-NH2) to the a-ketoglutarate turns it into glutamate alanine aminotransferase (ALT) is used for this reaction
what happens when oxaloacetate is used as the keto acid?
addition of NH2 will convert oxaloacetate to aspartate
enzyme used: aspartate aminotransferase (AST)
state the equation of alanine aminotransferase (ALT)
alanine + a-ketoglutarate pyruvate + glutamate
state the equation for aspartate aminotransferase (AST)
aspartate + a-ketoglutarate oxaloacetate + glutamate
what is deamination?
alternative pathway for removing amino group
what happens in deamination
amine group (NH2) removed from AA to form ammonia (NH3)
what are the effects of ammonia (NH3)?
very toxic
reduces TCA activity (depletion of substrate)
affects neurotransmitter synthesis
how do you get rid of NH3?
excreted in urine directly
can enter urea cycle to be excreted in urine
added to glutamate to make glutamine (safe N-store)
how is glutamine converted to glutamate?
glutamine –(glutaminase)–> glutamate + NH3
what happens to the produced glutamate?
glutamate a-ketoglutarate + NH4+
describe what happens in the urea cycle
converts ammonia into urea (soluble & inert - easy to excrete)
disposed as urine (kidney), converted to urea (liver)
where does the NH2 group of urea come from?
NH4+ (deaminate to NH3 and enter directly) or aspartate from oxaloacetate by transamination
what does defects in urea cycle cause? what do you treat with?
ammonia intoxication leading to tremors, slurred speech, blurred vision –> mental retardation (in children), seizures, coma
treat with low protein diet
what happens in phenylketonuria?
phenylalanine hydroxylase deficiency (phenyalanine –> tyrosine –> adrenaline etc.)
tyrosine is needed to make neurotransmitters & thyroid hormones (so becomes an essential AA)
PJU damages CNS, causing mental retardation
what happens in homocystinuria?
cystathionine ß-synthase (CBS) deficiency (requires vit B6)
homocysteine converted to methionine instead
cysteine is important for making proteins (fibrillin-1) in CT (so also affecting muscles, CNS, CVS)
how do you treat homocystinuria?
B6 supplements to help any remaining CBS get rid of homocysteine
What are the different lipids in the human body?
TAG (dietary lipid), phospholipids, ketones, cholesterols, vit ADEK
how are lipids stored? why
stored anhydrously in adipose tissue as they are hydrophobic
more energy than CHO as less reduced
what can lipids not be used in?
cells without itochondria e.g. RBCs or by CNS (can’t cross Blood Brain Barrier)
what are TAGs (from diet) broken down into and how?
broken down into 3 fatty acids + glycerol by pancreatic lipase in small intestines
what happens to the TAG once it’s broken down?
recombine into TAGs to be transported in chylomicrons to be stored in adipose tissues
how is TAG metabolism activated? inhibited?
by glucagon and adrenaline, inhibited by insulin
what happens to the glycerol and fatty acids once TAG is metabolised?
glycerol: enters glycolysis / gluconeogenesis
fatty acids: metabolised by liver, skeletal muscle, heart
How is fatty acid taken into correct location to be metabolised?
in mitochondria, too large to be transported across the mito membrane, so has to go through carnitine shuttle
Explain carnitine shuttle
fatty acid –(fatty acyl CoA synthase)–> fatty acyl CoA
carnitine + acyl CoA –(CAT1)–> CoA + acyl carnitine
acyl carnitine enters matrix
acyl carnitine + CoA –(CAT2)–> carnitine + acyl.CoA
once acyl.CoA is in the matrix, explain ß-oxidation
ß-oxidation oxidises FAs by repeatedly removing C2 molecules (acetyl) to combine to CoA to form acetyl CoA to enter TCA or synthesis of TAG or ketones
what does ß-oxidation produce?
FADH2
NADH
all can enter oxidative phosphorylation
how are ketone bodies produced?
acetyl CoA –(synthase)–> HMG CoA
HMG CoA –(HMG CoA reductase)–> cholesterol (INSULIN)
HMG CoA –(lyase)–> ketone bodies (GLUCAGON)
where and when are ketones produced?
when the body is starving (low insulin:glucagon)
produced in the liver
what are the normal ketone bodies value? in starved situation?
normal
describe ketones
water soluble, so can be transported in the blood from liver –> tissues
converted back to acetyl CoA in muscle, heart & brain
which organ can use ketones but doesn’t? why?
CNS can use ketones but ketone production means blood glucose concentrations are preserved for CNS
What causes diabetic ketoacidosis?
high rate of ß-oxidation of fats in the liver as there is not insulin being produced (normally type 1) so fats are used instead of glucose as glucose is not taken up into cells
Describe the formation of ketones
from fatty acids (from TAG) metabolism
fatty acid + CoA –(fatty acyl CoA synthase)–> fatty acyl CoA
fatty acyl CoA through carnitine shuttle into matrix using CAT 1 & 2 (acyl transported, there is CoA either side of matrix membrane
fatty acyl CoA –> acetyl CoA –(synthase)–> HMG (CoA) –(lyase)–> acetoacetate –> acetone
what happens during diabetic ketoacidosis? (presenting diagnosis)
ketones present in urine
acetone is volatile and may be present in breath - breathed out and smelt
What are the symptoms of diabetic ketoacidosis? what causes the symptoms?
hyperventilation, nausea, vomiting, dehydration, abdominal pain
caused by H+ ions associated with ketones producing metabolic acidosis (ketoacidosis)
What is used in fatty acid synthesis?
uses energy from ATP
reduces FAD & NAD+ to FAD2H & NADH
input pf 2 CoA
where does fatty acid synthesis take place?
in cytoplasm
acetyl CoA + oxaloacetate –> citrate to move from mitochondria to cytoplasm
How are fatty acids build up? what does it use?
2 carbons at a time using fatty acid synthase complex
Describe the process of fatty acid synthesis
acetyl CoA + CO2 –(acetyl CoA carboxylase)–> Malonyl CoA –(fatty acid synthase complex)–> 2 carbon atoms added to fatty A chain + CO2
What controls how fast fatty acids are synthesised?
acetyl CoA carboxylase (to malonyl.CoA)
aside from acetyl CoA carboxylase, what else regulates fatty acid synthesis?
- allosterically: high energy activate (citrate), low energy inhibits (AMP)
- covalent modification (adding / removing phosphate groups): insulin activates, glucagon/adrenaline inhibits
What are the main energy stores in the body?
TAGs (15kg), muscle protein (6kg), glycogen (0.4kg)
how do lipids travel around the body? why?
lipids are insoluble - need carriers
fatty acids bind to albumin
98% lipids are cholesterol (TAGs & cholesterol), so travel as lipoproteins
what is the structure of lipoproteins?
sphere with surface coat (shell) of phospholipids, cholesterol & apoproteins
and hydrophobic core (TAGs & cholesterol esters)
how do lipoproteins maintain their structure?
if spherical shape is maintained, dependent on ratio of core:surface lipids
lipids from hydrophobic core if taken up by cells then surface coat must also be reduced - by transfering to different particles or cell membrane
core can only be removed by lipases and transfer proteins
what do chylomicrons transport?
DIETary TAGs from intestine to tissues e.g. adipose
what do VLDLs transport
TAGs synthesised in liver to adipose for storage
what do IDL transport?
short-lived precursor for LDL
transport of cholesterol SYNthesised in the liver to tissues
What do LDL transport
cholesterol synthesised in liver to tissues
same as IDL
what do HDL transport?
transport excess tissue cholesterol to liver for disposal as bile salts and to any cells requiring additional cholesterol
which enzyme is responsible for removing core TAGs from lipoprotein particles? what up regulates this enzyme? how does it function?
lipoprotein lipase
found in inner surface of capillaries of adipose tissue & muscle
synthesis increased by insulin
lipoprotein lipase hydrolyses TAGs to release fatty acids and glycerol
what happens to the fatty acid and glycerol hydrolysed by lipoprotein lipase?
fatty acids are taken up by tissues and glycerol transported to liver
how is stability of the surface : core ratio restored?
when surface lipid is converted to core lipid
via enzyme LCAT
important in the formation of lipoprotein particles (maintaining structure)
what does LCAT do?
converts cholesterol (surface) to cholesterol ester (core) using fatty acid derived from lecithin (phophatidylcholine)
what does deficiency of LCAT lead to?
unstable lipoproteins of abnormal structure and a general failure in the lipid transport processes
what is dyslipoporteinaemia?
any defect in the metabolism of the plasma lipoproteins
What is hyperlipoproteinaemias?
raised levels of plasma lipoproteins
what is type 1 dyslipoproteinaemia? (hyperlipoproteinaemia)
defective lipoprotein lipase
causing chylomicrons in fasting blood
what is type 2a hyperlipoporteinaemia? what is it referred to as? associated risks?
defective LDL receptor
familial hypercholesterolaemia
raised LDLs in blood (as not taking up by cells) leading to increased risk of coronary artery disease (plaques building up)
what are the signs of hypercholesterolemia?
xanthoma, xanthelasma, corneal arcus
how do atheromas form?
endothelium damage leading to LDLs enter into blood vessel wall (now there is opening in endothelium)
LDLs become oxidised and then taken up by macrophages
macrophages become foam cells
foam cells accumulate to form plaques in vessel walls
what can cause endothelial damage?
hyperlipidaemia, hypertension, smoking, toxins, haemodynamic factors, viruses, immune reactions
what are the treatments of hyperlipoproteinaemias?
diet: reduce cholesterol, sat fats
lifestyle: increase exercise, reduce smoking
statins: inhibit HMG CoA reductase enzyme - decrease cholesterol production
what are ROS and how are they formed?
during ox/phos by radiation or chemicals
O2 species with a single unpaired electron (highly reactive)
what can ROS react with? what does it form?
react with lipids in cell membranes –> atherosclerosis
react with DNA to induce mutations
cause protein damage
when can ROS be useful?
in WBCs to produce an oxidative burst to destroy bacteria
how are superoxides formed? (O2.-)
during ox/phos - some electrons escape the ETC and bind only to oxygen
forming superoxide radical (O2 + e- –> O2.-)
unpaired electron make them highly reactive and damaging
how is superoxide broken down? (to make it safe)
Superoxide –(Superoxide dismutase)–> hydrogen peroxide (H2O2)
H2O2 still a ROS
H2O2 –(catalase)–> H2O + O2
how are hydroxyl radicals (.OH) produced and how do you get rid of them?
produced from H2O2 or radiation splitting H2O
v damaging, no enzymes to eliminate
need antioxidants to reduce them - glutathione (GSH) is the main antioxidant, so require NADPH to help free GSH
what is the reaction between NADPH and glutathione?
GSH –(GSH peroxidase)–> H2O2 to H2O
GSSH –(GSH reductase)–> 2 x GSH (NADPH –> NADP)
what happens to bile salts produced?
bile salts (deposition of excess cholesterol) bind to GI, causing more cholesterol to be broken down to form the bile salts that have been excreted / lost from binding to GI
