Revision Session Questions Flashcards
Explain why lactic acid (lactate) production is important in anaerobic glycolysis
Allows ATP to still be produced in absence of oxygen (oxygen supply inadequate or in cells without mitochondria)
Pyruvate reduced to lactate via lactate dehydrogenase
Describe the key features of glycolysis:
What is it
Where it occurs / where it occurs in the cell
Functions
Features
Central pathway of carbohydrate metabolism
Occurs in all tissues
Occurs in cell cytoplasm
Functions: Oxidise glucose Produce 2NADH Synthesise 2ATP (net) Produce C6 & C3 intermediates (glycerol phosphate, 2,3-BPG)
Features:
Exergonic (produces energy)
Oxidative
Splits C6 to 2xC3 (2 x pyruvate): no loss CO2
With one additional enzyme, only pathway that can operate anaerobically
Irreversible pathway
What are the following intermediates of glycolysis used for:
Glycerol phosphate
2,3-BPG
Glycerol phosphate:
Synthesis of TAGs in liver & adipose tissue
Store of lipid in adipose tissue dependent on rate of glycolysis
Liver can phosphorylate glycerol using glycerol kinase & ATP, so less dependent on glycerol phosphate (enzyme not present in adipose tissue)
2,3 BPG:
Important regulator in oxygen affinity of Hb
Produced from 1,3 BPG in rbc’s
Explain how blood conc of lactate is normally controlled
Normal physiological conditions:
50g lactate produced by rbc’s / skin / brain / skeletal musc / GIT
Rate of lactate production = rate of utilisation (plasma conc <1mmol/l)
lactate released into circulation Transported to liver, heart musc, (kidney) Converted back to pyruvate In heart musc: oxidised to CO2 In liver/kidney: converted to glucose
What happens when plasma lactate is increased:
What situations does this occur
What elevation is significant & why
Increased production of lactate:
Strenous exercise, hearty eating, shock, congestive heart disease
Increased utilisation:
Liver disease, thiamine deficiency, alcohol metabolism
> 5mmol/L
Exceeds renal threshold for lactate
Begins to affect buffering capacity of plasma (lactic acidosis)
Describe the key features of oxidative phosphorylation (i.e. The process of how ATP is produced)
Electrons in NADH have more energy than in FAD2H
So NADH uses 3PTCs; FAD2H only uses 2
Greater the p.m.f. The more ATP synthesised
Oxidation of 2M NADH = synthesis 5M ATP
Oxidation of 2M FAD2H = synthesis 3M ATP
Oxygen is the final electron acceptor, so oxygen is needed
Free electrons can escape and react with oxygen to produce harmful intermediates: ROS
Explain why the pentose phosphate pathway is an important metabolic pathway in some tissues:
What is produced & what are they used for
When is this pathway favoured
What is the key enzyme & what is converted to what
NADPH: Antioxidant
Ribulose 5 P: make nucleotides for DNA synthesis
When more NADPH is needed (rather than more ATP)
(Ribose sugar can be made via other pathways)
Glucose 6 phosphate dehydrogenase
Describe the mechanism of action of steroid hormones
What difficulty is there with targeting steroids
Steroids are lipid soluble & can cross the cell membrane (diffuses into cell)
Steroid binds to receptor in cytosol or nucleus
(Therefore, although can enter most cells, will only have effect on those with receptor)
Activated steroid receptor binds to DNA: can either switch on or switch off protein synthesis for a specific protein (e.g. Enzyme)
Can be difficult to target steroids to specific tissues: get side effects
Describe the concept of crossover & give 2 examples
At high concs, specific steroid hormones can cross over & act at diff steroid hormone receptor
(Because of homology between structurally similar steroids/receptors).
E.g. Cortisol (a glucocorticoid):
At high levels can bind to mineralocorticoid receptors, causing mineralocorticoid effects
(increased plasma Na+, decreased plasma K+)
draws water into circulation = higher blood vol = hypertension
E.g. ACTH:
At high levels, can bind to melanocortin receptors
Causes alpha-MSH type effects = hyperpigmentation
Describe the key features of amino acid metabolism:
How excess amino acids are processed
How toxic intermediates are processed
Constant turnover of proteins (making/breaking) makes free aa’s
Can be used to make other proteins
Rich diet = excess aa’s
Liver disposes of excess aa’s
Prob: amine group potentially toxic (transamination or deamination)
Enzymes remove NH2 grp leaving C skeleton, with 2 poss pathways:
Ketogenic aa’s (e.g. Leucine, lysine):
used to make ketone bodies from acetyl CoA
Glucogenic aa’s (e.g. Glutamate, glutamine):
can make glucose (glucoenogenesis)
Some aa’s are both ketogenic & glucogenic:
(e.g. Isoleucine, penylalanine, tyrosine)
Describe transamination
Transfer of amino group to a keto-acid
Uses alpha ketoglutarate or oxaloacetate (TCA intermediates)
Converts range of aa’s to glutamate or aspartate: useful products
(Can feed into urea cycle)
aa + alpha-ketoglutarate -> glutamate + keto acid
aa + oxaloacetate > aspartate + keto acid
Process is reversible
Describe 2 key enzymes of transamination & what they can be used for clinically
Alanine aminotransferase (ALT) Converts alanine to glutamate
Aspartate amino transferase (AST)
Converts glutamate to aspartate
ALT & AST levels measured in plasma: liver function test
(Liver damage = enzymes present in blood)
Describe the process of deamination
Disposal of amine group (NH2)
Removed from amino acid to form ammonia (NH3)
Converted to ammonium ion (NH4+)
These are very toxic (esp to neurones) & must be removed/converted to non-toxic products:
Glutamate -> aspartate -> urea cycle -> urea (water soluble)
(Ammonia + aspartate -> urea)
(Urea cycle can be up/down regulated)
Glutamate -> glutamine (good store / transport for ammonia)
Describe the key enzymes of deamination
L & D amino acid oxidases:
aa -> keto acid + NH3
Glutaminase:
Glutamine -> glutamate +NH3
Glutamate dehydrogenase:
glutamate -> alpha-ketoglutarate + NH3
Ammonia released is excreted in urine
Describe the process of ammonia detoxofication
Initially NH3 used to synthesise glutamine
Then NH3 (released from glutamine) either excreted directly or converted to urea
