BIOCH Y1 S1: Metabolism Flashcards
1
Q
3 main fuel sources in body
A
- glucose
- proteins
- lipids
2
Q
glycolysis
A
- glucose (6C) > 2 pyruvate (3C each)
- cytosol (aerobic or anaerobic)
- inputs: glucose (6C), 4 ADP+Pi, 2NAD+
- outputs: 2 pyruvate (3C), 2ATP (net), 2NADH
- first, 2 ATP are used. Then 2NADH are produced. Then 4 ATP are produced
- rate-limiting enzyme: phosphofructokinase-1 (PFK-1)
3
Q
fate of pyruvate (aerobic)
A
- pyruvate oxidised to 2 acetyl-CoA (2C) and 2 CO2 in mitochondrial matrix (exergonic)
- produces 2 NADH
- needs pyruvate dehydrogenase which needs thiamine (B1)
4
Q
fate of pyruvate (anaerobic/fermentation/reduction)
A
- pyruvate reduced to lactate (exergonic) in cytosol of muscles
- requires lactate dehydrogenase
- 2 NADH > 2 NAD+
- reversible
5
Q
key features of citric acid (Krebs) cycle
A
- acetyl-CoA oxidised to 2 CO2 (since it’s 2C molecule) and water in the mitochondrial matrix
- inputs: acetyl-CoA, FAD, 3 NAD+
- outputs: 2 CO2, H2O, 3 NADH, FADH2, 1 GTP, 1 ATP
- acetyl-coA makes citrate with the help of oxaloacetate
6
Q
how does natural uncoupling of mitochondria work
A
- natural uncouplers e.g. thermogenin protein found in the brown fat of newborn mammals
- provide alternative proton channel so some protons are lost as heat energy
7
Q
electron transport chain (oxidative phosphorylation)
A
- inner mitochondrial membrane (cristae)
- electrons move across complexes I-IV, causing H+ ions to be pumped into the intermembrane space
- H+ ions are NOT pumped by complex II
- O2 (final e- acceptor) combines w/ 2 H+ to form 2x H2O in matrix
- H+ ions have been moving against conc grad (proton motive force) so only way for them to come back into matrix (coupling) is via ATP synthase (passive) > drives synthesis of ADP + Pi into ATP
8
Q
inputs and outputs of the electron transport chain
A
- inputs: oxygen, ADP + Pi, NADH, FADH2, O2
(1 NADH > 2.5 ATP and 1 FADH2 > 1.5 ATP) - outputs: 3 NAD+, 1 FAD, H2O and GTP
9
Q
what is uncoupling of mitochondria
A
- when ETC is uncoupled from the process of ATP synthesis
- some protons don’t come back into matrix for ATP synthesis, they are dissipated in the form of heat e.g. for hibernation
10
Q
in one cycle of the CAC and its associated pathways, how much ATP is produced?
A
- 10 ATP
- 1 ATP, 3 NADH and 1 FADH2 are produced from the CAC
- in ETC, each NADH produces 2.5 ATP and each FADH2 produces 1.5 ATP, therefore we end up with an additional 9 ATP so 9+1=10
11
Q
glycogenesis
A
- synthesis of glycogen by glycogen synthase
- formed when there is excess energy
- glycogen mostly found in cytosol of liver and muscle cells
12
Q
glycogenolysis
A
- glycogen mobilised into glucose-6-phosphate
- if in liver: G6P hydrolysed to glucose using glucose-6-phosphatase to help maintain BGL etc
- if in muscles: G6P can directly enter glycolysis b/c there is no G6P-ase > provides energy for muscle contractions
13
Q
gluconeogenesis
A
- slow glucose synthesis using endogenous non-carbohydrates (liver cytosol) during starving
- uses energy from metabolism of fatty acids
- uses carbon skeletons from pyruvate, lactate, amino acids and glycerol (via DHAP)
14
Q
gluconeogenesis using pyruvate
A
- 7/10 enzymatic glycolysis reactions are reversible
- reversal of glycolysis except 3 bypasses are required
- needs ATP from oxidation of fatty acids and NADH
15
Q
gluconeogenesis using lactate
A
- Cori cycle
- glycogen in muscles is mobilised to form glucose
- glucose undergoes glycolysis to produce pyruvate
- pyruvate is reduced to form lactate (anaerobic in muscles)
- lactate is transported to liver to avoid cramps
- lactate undergoes gluconeogenesis to form glucose
- glucose transported back into muscle for glycogenesis
16
Q
why are fatty acids a good fuel?
A
- carry more energy per carbon b/c they are more reduced
- long carbon chains have more energy
- carry less water b/c non-polar > more efficient
- therefore better long-term energy source/storage compared to glucose
17
Q
how are dietary lipids metabolised
A
- TAGs emulsified into micelles (droplets) by bile
- lipase in small intestine breaks micelles > glycerol + fatty acids
- packaged into chylomicrons which transport in LYMPH
18
Q
lipogenesis
A
- fatty acid formation in liver cytoplasm, occurs when there is excess energy
- rate limiting step: synthesis of malonyl-CoA by acetyl-coA carboxylase
- acetyl-CoA > malonyl-CoA > fatty acid
- 2 carbons are added to the fatty acid chain each time to form palmitate (16C) FA
- uses 8 acetyl Co-A
- each addition of 2C uses 2 ATP and 1 NADPH
19
Q
TAG synthesis
A
- occurs in liver + adipose tissue in well-fed state, requires glycolysis to occur
- liver: glycerol + fatty acids + ATP > TAGs
- adipose: glycolysis intermediate + NADH + fatty acids > TAGs
20
Q
beta oxidation
A
- occurs in mitochondrial matrix (short chain FAs) or peroxisome (longer chain FAs)
- inputs: FAD, NAD+, H2O, fatty acids, CoA
- each time it is oxidised, 2 carbons are removed
- each round produces one acetyl-coA (+ one extra @ end), one NADH and one FADH2
- promoted by glucagon, inhibited by insulin
21
Q
cholesterol synthesis
A
- acetyl-CoA > cholesterol
- uses enzyme HMG-CoA reductase
- stimulated by insulin
- occurs in liver, adrenal cortex and gonads
22
Q
how are amino acids metabolised?
A
- broken down into amino group and carbon skeleton
- amino group undergoes glucose alanine cycle (for deamination/transamination) > transported to liver > excretion via urea cycle
- carbon skeletons are either glucogenic ( > sent to liver for gluconeogenesis) or ketogenic ( > ketone bodies)
23
Q
glucose alanine cycle
A
- amino acids from muscle protein are transaminated to glutamate
- glutamate combines w/ pyruvate and helps transport amino groups to liver for excretion via urea cycle
24
Q
function of the liver
A
- hepatocytes process fatty acids, monosaccharides and amino acids - either metabolise them or transport them to other tissues depending on needs
- converts nitrogen to excess urea
- distributes ketone bodies
- store nutrients
- detoxification: e.g. amino group from AAs sent to urea cycle
25
Q
function of adipose tissue
A
- synthesises, stores and mobilises triacylglycerols (TAGs)
26
Q
structure and function of white adipose tissue (WAT)
A
- S = large spherical cells filled w/ one lipid droplet, mitochondria and large nucleus squeezed to periphery
- F = TAG storage
27
Q
structure and function of brown adipose tissue (BAT)
A
- S = smaller, less round cells filled w/ several lipid droplets, have more mitochondria and brown colour due to cytochrome content. found primarily in newborns + around the kidneys and spine
- F = expresses uncoupling protein thermogenin which dissipates H+ gradient in mitochondria, inhibiting ATP synthesis > energy instead released as heat (thermogenesis)
28
Q
protein metabolism in adipocytes
A
- does not feature in adipocytes
29
Q
slow-twitch myocytes
A
- many blood vessels and mitochondria
- mitochondria provide energy via slow and steady ETC
30
Q
fast-twitch myocytes
A
- less mitochondria and lower oxygen delivery
- uses ATP faster and fatigues faster due to higher demands and lower oxygen delivery
- endurance training can increase mitochondria
31
Q
primary energy source for: body, brain, RBC, heart, skeletal muscles in well fed vs starving state
A
- body: lipids (well fed) and glucose (starve)
- brain: glucose (well fed) and ketone bodies (starve - only other thing that can cross BBB)
- RBC: always glucose (no organelles to metabolise other stuff)
- skeletal muscles: glucose and lipids (well fed), protein (starvation)
- heart: lipids (well fed) and glucose/ketone bodies (starve)
32
Q
why does rapid breathing continue after vigorous exercise?
A
- extra oxygen used for oxidative phosphorylation to build proton gradient and replenish ATP
- ATP used for gluconeogenesis to use up lactate and restore muscle glycogen
33
Q
energy for muscles at diff stages of a run
A
- 0s: dietary lipids
- sprint @ start: creatine phosphate
- 2m: anaerobic respiration (glucose)
- 5m: glycogen mobilisation > aerobic respiration (glucose)
- 30m: 1:1 carbs and stored lipids
- 45m: lipids
34
Q
can RBCs oxidise fatty acids?
A
no b/c don’t have any organelles, instead rely on glucose as a source of energy - highest rate of glucose utilisation of any cell in the body
35
Q
2 metabolic pathways for glucose in RBCs
A
- glycolysis (anaerobic)
- pentose phosphate pathway
36
Q
2 types of cells in the pancreas and where they’re found
A
- alpha cells: release glucagon when BGL are low
- beta cells: release insulin when BGL are high
- both found in the islets of Langerhans in pancreas
37
Q
lipoprotein functions
A
- albumin: transports FFAs from adipose tissue to other tissues during mobilisation
- chylomicron (synthesised in intestine): transport dietary TAGs from intestine to tissues via LYMPH
- VLDL (synthesised in liver): transports TAGs and some cholesterol from liver to tissues
- LDL (synthesised in blood): transports cholesterol from liver to tissues (bad)
- HDL (synthesised in liver and small intestine): transports cholesterol from tissue to liver to be excreted (good)
38
Q
apolipoprotein
A
- protein part of a lipoprotein
39
Q
processes stimulated when insulin is high
A
- glycogenesis
- TAG synthesis
- lipogenesis
- glycolysis
- mostly biosynthetic processes (anabolic) during well-fed state
40
Q
what are acetone, acetoacetate, beta-hydroxybutyrate?
A
ketone bodies
41
Q
can ketone bodies cross the blood-brain barrier?
A
yes
42
Q
situations where ketones will be high
A
- severe starvation
- alcohol
- diabetes
43
Q
alcohol metabolism
A
- ethanol > (alcohol dehydrogenase) acetaldehyde > (aldehyde dehydrogenase) acetate > acetyl-coA
- both of these steps use NAD+ > deficit inhibits CAC so can’t make glucose > acetyl-coA produces fatty acids or ketone bodies instead (ketosis)
- produces lactate (acidosis > tachypnoea to compensate) from pyruvate to replenish NAD+, further reducing the pyruvate & oxaloacetate available for gluconeogenesis > hypoglycaemia
44
Q
medication to give for alcohol poisoning
A
- Thiamine (vit B1): needed by pyruvate dehydrogenase to produce acetyl coA, converts NADH to NAD+
- bicarbonate to increase blood pH
45
Q
symptoms of alcohol poisoning
A
slurred speech, tachypnoea, trouble staying conscious (not getting hungover)
46
Q
how does alcohol affect lipid metabolism
A
- lack of NAD+ inhibits B-oxidation
- FA buildup in liver > cirrhosis (scarring and inflammation)
- FAs are stored as TAGs > transported in the blood (hyperlipidaemia)
- histology shows lipid droplets in hepatocytes
47
Q
which organ can’t use ketone bodies?
A
- liver
- it’s the only organ that produces them, but can’t use them b/c it lacks the enzyme
48
Q
3 hours after eating a meal, what is the major source of energy?
A
- mobilisation of liver glycogen
- not TAGs because these are generally used in longer times of starvation or after 5+ hours of sitting
49
Q
difference b/n digestion and mobilisation of carbs
A
- digestion = breakdown in GIT, produces glucose which is then absorbed into the blood
- mobilisation = breakdown of stored carbs, produces G6P
50
Q
‘asian flush’ syndrome occurs due to a deficiency in which enzyme?
A
- acetaldehyde dehydrogenase
- (type of aldehyde dehydrogenase)
51
Q
pentose phosphate pathway
A
- breakdown of glucose, forms NADPH
- secondary glucose metabolism for RBCs
- also used in times of enzymatic abnormalities
52
Q
what compound can be used in both CAC and gluconeogenesis?
A
oxaloacetate
53
Q
how does atherosclerosis occur?
A
- phagocytes engulf oxidised LDL
- aggregate and stick to ECM > form foam cells
