Self assessment Qs Flashcards
Whats the energy / fuel storage roles of: CNS Heart muscle Skeletal muscle Liver Adipose tissue
CNS:
Energy from glucose (also ketone bodies under certain conditions).
No fuel storage: requires continuous supply of fuels and oxygen.
Heart Muscle:
Energy from glucose, lactate, fatty acids or ketone bodies.
No fuel storage: requires continuous supply of fuels and oxygen.
Skeletal Muscle:
Energy from glucose, fatty acids or ketone bodies.
Muscle protein can be used in emergency.
Can oxidise glucose to lactate under anaerobic conditions.
Stores glucose as glycogen and some triacylglycerol.
Liver:
Energy from fatty acids, amino acids or alcohol.
Can use galactose and fructose.
Makes glucose from lactate, glycerol and amino acids.
Makes ketone bodies, cholesterol and triacylglycerols.
Stores glucose as glycogen.
Adipose tissue:
Energy from glucose or fatty acids.
Stores fuel in the form of triacylglycerols.
How are fuel molecules oxidised during catabolism
electrons/protons transferred initially to carrier molecules, that become reduced.
Major carrier molecules (in reduced form): NADH, NADPH, FAD2H
Total conc of carrier molecules constant, so must cycle btw oxidative & reductive processes to maintain cell function.
Reactions that serve to reoxidise reduced carrier molecules:
Reduction of substrate (e.g.pyruvic acid - lactic acid)
Biosynthetic reactions involving reduction (e.g. FA & cholesterol synthesis)
Oxidative phosphorylation (ETC: drives ATP synthesis)
Compare & contrast the functions of glycolysis in:
Adipose tissue
Skeletal muscle
Red blood cells
Produce ATP (by SLP) in all 3 tissues:
Rbcs: only mechanism for ATP production
Skeletal: enables ATP production to occur in anaerobic conditions
Adipose: minor route for ATP production
Produces intermediates in rbcs & adipose tissue:
2,3-bisphosphoglycerate produced from 1,3-BPG in rbcs & important in regulating (decreasing) oxygen affinity of Hb
Glycerol phosphate produced from dihydroxyacetone phosphate in adipose tissue & used in esterification of FAs to produce triacylglyerols
List end products of glycolysis under aerobic & anaerobic conditions in red blood cells & skeletal muscle
RBCs:
Aerobic: lactate
Anaerobic: lactate
Skeletal:
Aerobic: pyruvate
Anaerobic: lactate
Describe the basis of re-feeding syndrome in Kwashiorkor
protein deficient child.
protein given: broken down & stored as lipids in the liver.
cannot be transported out of liver; insufficient proteins in blood to carry them = fatty liver.
Also, because of impaired liver function, aa’s cant be broken down effectively, = increased ammonia waste product (urea cycle disrupted)
Why does a child with Kwashiorkor have a fatty liver?
Protein deficient but enough energy store from carbs
Not able to synthesise hormones & haemoglobin
Break down peripheral skeletal muscle
No glucose: Metabolising fat in liver to produce ketones.
No proteins to transport in bloodstream, So accumulates in liver.
Explain how electron transport & ATP synthesis are coupled
Proton motive force:
Free energy from electron transport used to move protons from inside to outside of inner mitochondrial membrane.
Membrane impermeable to protons.
As electron transport continues, conc of protons outside inner membrane increases
PTC therefore transform chem. bond energy of electrons into electro-chemical gradient
Protons can normally only re-enter mitochondrial matrix via ATP SYNTHASE enzyme complex (Drives synthesis of ATP from ADP + Pi).
ET & ATP synthesis tightly coupled.
Mitochondrial conc of ATP important in regulating both processes.
Describe the key features of electron transport and explain how the proton motive force is produced
Electron transport: electrons transferred from NADH (and FAD2H) sequentially through series of multi-component complexes to molecular oxygen with the release of free energy.
free energy used to move protons from the inside to the outside of the inner mitochondrial membrane.
membrane itself impermeable to protons
as electron transport proceeds, proton conc on outside of inner membrane increases.
chemical bond energy of electrons transformed into electro-
chemical potential difference of protons.
= proton motive force
Describe the relationship between electron transport and ATP synthesis.
chemical bond energy of e- in NADH & FAD2H used to drive ATP synthesis in final stage of catabolism (oxidative phosphorylation). occurs in mitochondria
involves highly organised multi-component systems.
Two processes involved: electron transport & ATP synthesis.
p.m.f. created by electron transport, forces protons back
into the mitochondrial matrix thru ATP synthase complex, driving synthesis of ATP from ADP and Pi.
Normally ET & ATP synthesis tightly coupled/controlled: one doesnt occur without the other.
Explain how coupling between ETC and ATP synthesis is altered during thermogenesis in brown adipose tissue mitochondria.
inner mitochondrial membrane of brown adipose tissue has, in addition to the ATP synthase complex, special proton conductance protein (thermogenin)
allows controlled re-entry of protons into the mitochondrial matrix without driving ATP synthesis
i.e. acts to uncouple ATP synthesis from ET.
This protein used to activate heat production (non-shivering thermogenesis) in cold environments.
In response to cold, norepinephrine released from the sympathetic NS. stimulates lipolysis, releasing FAs to provide fuel for oxidation in brown adipose tissue.
As a result of beta oxidation of FAs, NADH & FAD2H formed, driving ET and increasing p.m.f.
However, norepinephrine also activates thermogenin, allowing
protons to re-enter mitochondrial matrix without driving ATP synthesis. dissipates p.m.f as heat
Explain why cyanide is toxic to cells.
Cyanide blocks NADH & FAD2H oxidation
Inhibits respiratory chain at cytochrome oxidase/cytochrome aa3
prevents generation of p.m.f. and hence ATP synthesis.
Without ATP generation cell structure and function impaired
cell death rapidly ensues.
Explain The effects of pesticides on metabolism
Aromatic weak acids like 2-DNC (and 2,4-DNP) readily penetrate mitochondrial inner membrane & act as uncoupling agents
i.e. collapse p.m.f. and cause uncontrolled respiration
This consumes large amounts of:
metabolic fuels (esp FAs, derived from fats stored in adipose tissue - therefore absence of subcutaneous fat)
And
oxygen (would lead to hypoxia but prevented by increased pulmonary activity).
As much less ATP than normal made by OP under these conditions, energy lost as heat and body temp rises.
When attempts to combat this by increased sweating eventually
fail, the patient falls into a coma and dies.
Compare and contrast triacylglycerols and glycogen as energy storage materials in man.
Triacylglycerols and glycogen both energy storage molecules. Triacylglycerols:
major energy storage molecules (70kg man normally stores 10-15kg)
stored in highly specialised tissue (adipose)
more efficient from of energy
hydrophobic and stored in an anhydrous form
more reduced than glycogen & contain more stored energy per C-atom
Glycogen: Less stored (70kg man stores 0.4 kg) stored in tissues such as the liver and skeletal muscle, which have other important functions. Less efficient storage polar and stored with water.
Describe, in outline, the processes involved in the utilisation of the triacylglycerols stored in adipose tissue by muscle cells.
During prolonged aerobic exercise, starvation, stress situations and lactation:
adipose tissue triacylglycerols hydrolysed by the enzyme (hormone-sensitive) lipase to release FAs and glycerol (lipolysis)
activated by adrenaline, glucagon, growth hormone, cortisol and thyroxine
inhibited by insulin.
FAs carried to tissues such as muscle via blood stream, bound non-
covalently to albumin.
albumin-bound FAs = non-esterified fatty acids (NEFA) or free fatty acids (FFA).
glycerol not used by muscle cells but metabolised by liver cells.
Many tissues incl heart and skeletal muscle use the FAs as source of energy.
FAs oxidised to release energy = beta oxidation: occurs in mitochondria.
In order to be metabolised, FAs activated by linking to CoA in reaction
that requires ATP.
activated FAs transported into mitochondria via specialised transport process that uses carnitine.
rate of FA transport into mitochondrion determines rate of subsequent oxidation.
Once inside mitochondrion, oxidation of FAs occurs via sequence of reactions (beta oxidation pathway); oxidises the FA & removes a C2 unit (acetate).
shortened FA cycled thru reaction sequence repeatedly removing a C2 unit each turn of cycle until only two C atoms remain.
List the products that can be synthesised from acetyl~CoA and explain why it cannot be converted to glucose in man.
Acetyl~CoA produced by catabolism of FAs, sugars, alcohol & certain aa’s
can be oxidised via stage 3 of catabolism.
also an important intermediate in lipid biosynthesis.
major site of lipid synthesis in the body = liver (some in adipose
tissue)
most lipids (not polyunsaturated FAs) can be synthesised.
Acetyl~CoA cannot be converted to pyruvate in man because enzyme pyruvate dehydrogenase irreversible & no other mechanism for by-passing this enzyme.
Since it cannot be converted to pyruvate it cannot be converted to glucose.
Explain how:
some amino acids can be converted to glucose (glucogenic)
some can be converted to ketone bodies (ketogenic)
others can be converted to both glucose and ketone bodies (glucogenic and ketogenic).
Amino acids that produce acetyl~CoA (e.g. leucine, lysine) =ketogenic: acetyl~CoA can be used for the synthesis of ketone bodies.
Amino acids that give rise to the other products (glutamic, aspartic, serine) = glucogenic
can be used for glucose synthesis by gluconeogenesis.
Some of the larger amino acids (isoleucine, threonine, phenylalanine, tyrosine and tryptophan) = both ketogenic and glucogenic
give rise both to acetyl~CoA and one of the other organic precursor molecules.
Describe in general terms how amino acids are degraded in the body and list the major products of their degradation.
Degraded to smaller molecules largely in the liver.
Each aa has its own pathway of catabolism
but the pathways share common features:
C-atoms are converted to intermediates of carbohydrate metabolism (glucogenic aa’s) or lipid metabolism (ketogenic aa’s)
N-atoms usually converted to urea for excretion in the urine
but some may be excreted directly as ammonia
and some may be converted to glutamine and used for the synthesis of purines and pyrimidines.
first step in the various pathways usually involves removal of the –NH
2 group by transamination or deamination.
Products = urea, pyruvate, acetyl~CoA, alpha-ketoglutarate, oxaloacetate, succinate and fumarate.
Describe the processes that produce ammonia in the body.
Ammonia produced by:
deamination of aa’s
absorbed from gut where it is produced by bacterial action.
Several deaminase enzymes of varying specificity are found in the liver and kidney that react with aa’s to remove the NH2 grp as free NH3
(NH4+):
D-amino acid oxidases = low specificity enzymes that convert aa’s to keto acids and NH3
Glutaminase = high specificity enzyme that converts glutamine to glutamate + NH3
Glutamate dehydrogenase = high specificity enzyme that catalyses the reaction:
Glutamate + NAD+ + H2O -> apha-ketoglutarate +NH4+ + NADH + H+
important in aa metabolism by liver as involved in both disposal of
aa (glutamate alpha-ketoglutarate + NH4+ ) and synthesis of non-essential aa’s (alpha-ketoglutarate glutamate).
a 7-month old baby boy, developed normally until he was weaned at 6 months. Following the introduction of a high protein diet he had become irritable, lethargic and less alert and had begun to
vomit. He was admitted to hospital where he had episodes of screaming, listlessness and ataxia (uncontrolled limb movements) especially after a protein rich meal. His urine was persistently alkaline and contained a lower urea concentration than normal. His blood NH4+ and glutamine concentrations were increased but fell to normal when his protein intake was reduced. He was put on a special low-protein diet and his subsequent development was normal.
Explain the biochemical basis of this patient’s signs and symptoms.
signs and symptoms began when high protein diet was introduced and disappeared when protein intake was used:
suggest a defect in amino acidmetabolism.
The high blood NH4+ and glutamine and low urine urea concentration: suggest an inability to convert NH4+, produced from the catabolism of amino acids, to urea.
Thus, the problem is likely to be a partial defect in one of the enzymes of the urea cycle.
high blood ammonia associated with disturbances to CNS function (NH4+ interferes with energy metabolism in the CNS) and produced the symptoms of irritability, lethargy, screaming, listlessness and ataxia.
Explain how tissues obtain the lipids they need from lipoproteins.
Triacylglycerols obtained from chylomicrons and VLDLs by the extracellular enzyme lipoprotein lipase present in the capillary bed of the tissue.
This hydrolyses triacylglycerols to FAs and glycerol.
FAs taken up by tissues and re-esterified to triacylglycerols using glycerol phosphate, derived from glucose metabolism.
Cholesterol is obtained from LDLs by receptor mediated endocytosis. The LDL particles bind to LDL receptors on the surface of target cells. The receptor with its bound LDL is taken into the cell by endocytosis. The endosome is attacked by lysosomal enzymes releasing free cholesterol in the cell and destroying the receptor protein.
The cholesterol is converted to cholesterol esters for storage.
When the cell has enough cholesterol, cholesterol inhibits the synthesis of new LDL receptors and the uptake of cholesterol is reduced.
Explain why individuals with a defect in the enzyme lecithin-cholesterol
acyltransferase produce unstable lipoproteins of abnormal structure. What are the clinical consequences of this defect?
All mature lipoproteins found in normal human plasma are spherical particles that consist of a surface coat and a hydrophobic core. Lipoproteins particles are only stable if they maintain their spherical This is dependent on the ratio of core to surface lipids.
As the lipid from the hydrophobic core is removed and taken up by tissues the lipoprotein particles become unstable as the ratio of surface to core ipids increases.
Stability can be restored if some of the surface lipid is converted to core lipid.
This is achieved by the enzyme LCAT; important in formation of lipoprotein particles and in maintaining their structure.
The enzyme converts cholesterol (a surface lipid) to cholesterol ester (a core lipid) using fatty acid derived from lecithin (phophatidylcholine).
Deficiency of the enzyme = unstable lipoproteins of abnormal structure and a general failure in the lipid transport processes.
Lipid deposits occur in many tissues and atherosclerosis is a problem
Outline the pathways by which tissues obtain the cholesterol they need.
Direct synthesis from acetyl CoA within tissues.
Obtain cholesterol synthesised in the liver via LDLs.
List 3 signs or symptoms of a very high blood cholesterol
Corneal arcus
Xanthelasma and/or Tendon xanthoma
Accelerated development of atherosclerotic diseases
What classes of lipoprotein are present in the serum from a fasting blood sample taken from a normal individual?
LDL, VLDL & HDL (Not chylomicrons).
What is hyperlipoproteinaemia?
Any condition in which, after a 12 hour fast, the plasma cholesterol and/or plasma triglyceride is raised.
A 32 year old male came to see you in a general practice surgery. He was concerned that his father had died at the age of 50 from a heart attack and he wanted his blood cholesterol checked. You arrange for a fasting blood sample to be taken and sent to the Clinical
Chemistry Lab for analysis.
The laboratory reports the following results:
total serum cholesterol = 12 mM (reference range =
Blood glucose to check for fasting sample and/or diabetes.
Type IIa or familial hypercholesterolaemia.
