1
Q
what is oxidation of glucose?
A
The process of extracting energy from glucose molecules via metabolic pathways (glycolysis → pyruvate oxidation → TCA cycle → ETC → oxidative phosphorylation).
2
Q
overall goal of glucose oxidation
A
Convert the chemical energy in glucose into ATP, NADH, and FADH₂.
3
Q
What’s the overall equation for aerobic respiration?
A
C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O + ~30–32 ATP.
4
Q
where does each phase of glucose oxidation occur
A
Glycolysis= cytoplasm
Pyruvate Oxidation, TCA, ETC= mitochondria
5
Q
what is the starting molecule and end product of glycolysis
A
Glucose (6C) –> Pyruvate (3C)
6
Q
what are the 2 phases of glycolysis and their ATP use/ production
A
Investment= used 2 ATP
Payoff= Produces 4ATP and 2NADH
7
Q
net energy yield of glycolysis per glucose molecule?
A
2 ATP (net) + 2NADH
8
Q
key irreversible enzymes (regulatory steps) in glycolysis
A
Hexokinase / Glucokinase (Glucose → G6P)
Phosphofructokinase-1 (PFK-1) (F6P → F1,6BP)
Pyruvate kinase (PEP → Pyruvate)
9
Q
end product of glycolysis with O2 present
A
pyruvate (enters mitochondria)
10
Q
end product of glycolysis if O2 isn’t present
A
Lactate (in animals) or CO2 (in yeast)
11
Q
2 possible fates of pyruvate
A
Aerobic conditions: → Acetyl-CoA (via Pyruvate Dehydrogenase Complex)
Anaerobic in muscle: → Lactate (via lactate dehydrogenase)
12
Q
what enzyme converts pyruvate to acetyl-CoA?
A
Pyruvate Dehydrogenase Complex (PDC)
13
Q
what are the cofactors for PDC
A
TPP, FAD, NAD⁺, CoA, and lipoic acid.
14
Q
what’s the product of pyruvate oxidation?
A
1 Acetyl-CoA + 1 CO₂ + 1 NADH (per pyruvate).
15
Q
what are feeder pathways?
A
Metabolic routes that convert other nutrients into glycolytic intermediates.
Glycogen → Glucose-1-phosphate → G6P
Fructose → G3P or DHAP
Galactose → G6P
Mannose → F6P
Glycerol (from fats) → DHAP
16
Q
why are feeder pathways important?
A
They allow other carbohydrates and lipids to enter energy metabolism.
17
Q
What happens to pyruvate in aerobic metabolism? where does this occur
A
It’s converted to Acetyl-CoA → enters Citric Acid Cycle → NADH/FADH₂ → ETC → ATP.
Occurs in mitochondria
18
Q
main purpose of aerobic metabolism
A
Complete oxidation of glucose to CO₂ and capture energy as ATP.
19
Q
where does the citric acid cycle/ TCA/ Krebs occur?
A
mitochondrial matrix
20
Q
what enters the citric acid cycle, and what are the main products?
A
Acetyl-CoA (2C) combines with oxaloacetate (4C) → citrate (6C).
3 NADH
1 FADH₂
1 GTP (≈1 ATP)
2 CO₂
21
Q
key enzymes in citric acid cycle
A
Citrate synthase
Isocitrate dehydrogenase (rate-limiting)
α-Ketoglutarate dehydrogenase
Succinate dehydrogenase
22
Q
What’s the total ATP yield from one turn of the TCA cycle (including oxidative phosphorylation)?
A
~10 ATP (3 NADH × 2.5 + 1 FADH₂ × 1.5 + 1 GTP × 1).
23
Q
ETC Location, role and main complexes.
A
Inner Mitochondrial Membrane
Transfer electrons from NADH/FADH₂ to O₂, forming H₂O and pumping protons to create a gradient.
Complex I: NADH dehydrogenase
Complex II: Succinate dehydrogenase
Complex III: Cytochrome bc₁
Complex IV: Cytochrome c oxidase
24
Q
What is oxidative Phosphorylation, what drives it’s synthesis, and what is the input/ output per glucose yield
A
synthesis of ATP using the proton gradient generated by the ETC.
Proton motive force — H⁺ flows back through ATP synthase.
Input= NADH → ~2.5 ATP
FADH₂ → ~1.5 ATP
Glycolysis: 2 ATP + 2 NADH
Pyruvate oxidation: 2 NADH
TCA: 6 NADH + 2 FADH₂ + 2 GTP
≈ 30–32 ATP total
25
Why does anaerobic glycolysis yield less ATP?
NADH cannot enter ETC → regenerates NAD⁺ via lactate formation, no oxidative phosphorylation.
26
key goals of metabolic regulation
Maintain homeostasis (stable ATP, glucose, etc.)
Balance catabolism (breakdown for energy) and anabolism (biosynthesis)
Adapt to changes in nutrient availability, energy demand, and hormonal signals
27
allosteric regulation
Enzymes are activated or inhibited by metabolites (e.g., ATP, AMP, citrate).
Fast and reversible.
Example: ATP inhibits phosphofructokinase-1 (PFK-1).
28
covalent modification- metabolic regulation
Reversible phosphorylation/dephosphorylation changes enzyme activity.
Controlled by hormones (insulin, glucagon, adrenaline).
Example: Phosphorylase kinase activates glycogen phosphorylase.
29
Hormonal regulation
Coordinates metabolism across tissues.
Insulin → promotes anabolic pathways (glycolysis, glycogen synthesis).
Glucagon/adrenaline → promote catabolic pathways (gluconeogenesis, glycogen breakdown).
30
transcriptional control- metabolic regulation
Long-term regulation via changes in enzyme synthesis.
Example: Fasting increases expression of gluconeogenic enzymes.
31
compartmentalisation- metabolic regulation
Metabolic pathways occur in specific cellular locations (e.g., fatty acid oxidation in mitochondria; fatty acid synthesis in cytosol).
32
substrate availability- metabolic regulation
Concentration of substrates, cofactors, and oxygen affects flux through pathways.
33
Biochemical reactions can be regulated by:
Substrate concentration
Feedback Inhibition
Enzyme Activity
Protein Half- life
ATP/AMP levels
34
Glycolysis vs Gluconeogenesis energy status
Glycolysis= low ATP, high AMP
Gluconeogenesis= high ATP, low AMP
35
Glycolysis vs Gluconeogenesis hormones
Glycolysis= increased insulin
Gluconeogenesis= increased glucagon+ cortisol
36
Glycolysis vs Gluconeogenesis substrate availability
Glycolysis= increased glucose
Gluconeogenesis= increased lactate, alanine, glycerol
37
Glycolysis vs Gluconeogenesis key regulatory enzymes
Glycolysis= PFK-1 activated by AMP, F2,6BP
- Pyruvate kinase activated by F1,6BP
Gluconeogenesis= Fructose-1,6-bisphosphatase inhibited by F2,6BP and AMP
- PEP carboxykinase and pyruvate carboxylase activated by acetyl-CoA
38
Glycolysis vs Gluconeogenesis tissue
Glycolysis= liver + muscle (energy use)
Gluconeogenesis= Liver and kidney (glucose production)
39
insulin effect and mechanism
Stimulates glycogen synthesis
Activates protein phosphatase → dephosphorylates (activates synthase, inactivates phosphorylase)
40
Glucagon (liver) / Adrenaline (muscle) effects and mechanism
Stimulates glycogen breakdown
Activates cAMP → activates protein kinase A → phosphorylates (activates phosphorylase, inactivates synthase)
41
central role of the liver in metabolism
- digestion and absorption of nutrients
- nutrient transport to the liver
- metabolising nutrients or distributing them to extrahepatic tissues
42
glucose metabolism in the liver
- digestion and absorption
- phosphorylation
43
In the liver of a well fed person, excess acetyl CoA will be used to synthesise:
Cholesterol
44
When the demand for fuel rises, the triglyceride stores in the adipocyte are hydrolysed by
Lipases
45
How do fatty acids provide energy between meals?
During fasting or overnight, fatty acid oxidation generates most ATP. Hypoglycaemia triggers lipolysis—stored triacylglycerols are broken into fatty acids + glycerol, which are used for energy.
46
What happens to glycerol released from triglyceride breakdown?
Glycerol travels to the liver, where it is either:
Converted to glucose via gluconeogenesis, or
Oxidised for energy.
It contributes ~5% of total energy yield.
47
What is β-oxidation?
Process in mitochondria that removes 2-carbon units from the carboxyl end of fatty acyl-CoA, forming acetyl-CoA, NADH, and FADH₂ → energy via CAC and ETC.
48
List the steps of β-oxidation.
1. Dehydrogenation → acyl-CoA dehydrogenase → trans-enoyl-CoA (produces FADH₂)
2. Hydration → enoyl-CoA hydratase → hydroxyacyl-CoA
3. Dehydrogenation → β-hydroxyacyl-CoA dehydrogenase → β-ketoacyl-CoA (produces NADH)
4. Thiolysis → thiolase → releases acetyl-CoA
Cycle repeats until fully oxidised.
49
How are fatty acids activated and transported into mitochondria?
Activation: Fatty acyl-CoA synthase forms fatty acyl-CoA (in outer mitochondrial membrane).
Transport: Long-chain FA (>14C) need the carnitine shuttle.
Once inside, oxidised for ATP; if not activated, remains in cytosol.
50
What hormones mobilise stored triacylglycerols?
Glucagon and adrenaline bind adipose receptors → activate lipase enzymes → release free fatty acids + glycerol into blood for energy use by tissues.
51
When and how are ketone bodies formed?
Formed in liver mitochondria when acetyl-CoA accumulates (starvation or diabetes).
Acetyl-CoA → acetoacetate, D-β-hydroxybutyrate, acetone.
Transported in blood to tissues (except liver) as alternative fuel.
52
What are ketosis, acidosis, and ketoacidosis?
Ketosis: Normal adaptation to fasting (↑ ketone production).
Acidosis: Excess ketones lower blood pH.
Ketoacidosis: Dangerous, severe acidosis in uncontrolled diabetes/starvation.
53
What are the building blocks and types of lipids?
Building blocks: Fatty acids + glycerol.
Major types: Triglycerides, phospholipids, cholesterol, waxes.
Lipogenesis: Synthesis of FAs and triglycerides from excess carbohydrates.
Unsaturated FAs have double bonds → bent/kinked structure.
54
Why are fatty acids a crucial energy source?
High ATP yield (more than carbohydrates).
Provide energy during fasting or intense exercise.
β-oxidation → acetyl-CoA → CAC + ETC → ATP.
55
Sources of FAs?
Dietary fats
Stored lipids (adipose TAGs)
De novo synthesis (lipogenesis)
Autophagy (cellular fat recycling)
56
How are dietary fats digested and absorbed?
Biile salts emulsify fats → micelles.
Lipases hydrolyse triglycerides → FAs + monoacylglycerols.
Enter intestinal mucosa, re-esterified to TAGs → form chylomicrons.
Chylomicrons travel via lymph → tissues.
Lipoprotein lipase releases FAs for oxidation or storage.
57
What is fatty acid synthesis?
Occurs in cytosol of liver/adipose cells.
Converts acetyl-CoA + malonyl-CoA → long-chain FA using NADPH.
Endergonic & reductive (requires ATP + NADPH).
Not the reverse of β-oxidation.
58
How does fatty acid synthesis begin?
Pyruvate → acetyl-CoA in mitochondria.
Citrate carries acetyl units to cytosol.
ATP-citrate lyase converts citrate → acetyl-CoA (cytosol).
Acetyl-CoA used to initiate FA synthesis.
59
How is malonyl-CoA formed and why is it important?
Acetyl-CoA carboxylase (ACC) converts acetyl-CoA → malonyl-CoA.
Malonyl-CoA provides 2-carbon units for FA chain elongation.
Fatty acid synthase (FAS) catalyses conversion to palmitic acid.
Malonyl-CoA inhibits FA oxidation (blocks carnitine shuttle).
60
What are the steps in each FA synthase cycle?
Condensation – Acetyl-CoA + Malonyl-CoA → 4C chain (CO₂ released).
Reduction – Uses NADPH.
Dehydration – Removes H₂O.
Reduction – Uses NADPH again.
→ Chain extended by 2C per cycle until full length.
61
How is fatty acid synthesis regulated?
Allosteric:
Citrate activates ACC (signals energy surplus).
Long-chain FA inhibit ACC (feedback).
Hormonal:
Insulin activates synthesis.
Glucagon/adrenaline inhibit synthesis.
Nutritional:
High-carbohydrate diet ↑ synthesis; fasting ↓ it.
62
What is the difference between lipogenesis and FA synthesis?
FA synthesis: Creation of fatty acid chains from acetyl-CoA/malonyl-CoA.
Lipogenesis: Broader term — includes FA synthesis + triglyceride formation for storage.
63
Name the 5 key enzymes in FA metabolism.
Fatty acyl-CoA synthase – activates FA for oxidation.
Carnitine acyltransferase I – transports long-chain FA into mitochondria.
Acetyl-CoA carboxylase (ACC) – forms malonyl-CoA (rate-limiting for synthesis).
Fatty acid synthase (FAS) – elongates FA chain.
Hormone-sensitive lipase – mobilises stored TAGs.
64
what are the main components of AA
Amino group (–NH₂)
Carboxyl group (–COOH)
Central α-carbon
Side chain (R-group)
65
What are the four levels of protein structure?
Primary – amino acid chain
Secondary – α-helix or β-sheet
Tertiary – 3D folding
Quaternary – 2+ polypeptides in one protein
66
How do proteins fold?
Non-polar (hydrophobic) side chains cluster inside.
Polar groups face outward to form hydrogen bonds with water or polar molecules.
67
How is protein content measured?
Indirectly via nitrogen content using the factor 6.25 (because protein ≈16% nitrogen).
68
What is nitrogen balance?
Nitrogen balance = Nitrogen intake – Nitrogen excretion
69
What are sources of nitrogen loss?
Urine, creatinine, uric acid, ammonia, feces, and sweat.
70
What are the three nitrogen balance states?
Positive: growth, pregnancy, recovery, resistance training, ↑ insulin/testosterone/HGH
Neutral: healthy adult meeting protein and energy needs
Negative: illness, burns, injury, low protein intake, kidney disease, ↑ cortisol/thyroid hormones
71
Where does amino acid metabolism begin?
In the GI tract – dietary proteins are broken down into amino acids, which enter the liver via the bloodstream.
72
What is the first step in amino acid catabolism?
Removal of the α-amino group by transamination (via aminotransferases).
73
What is transamination, and what coenzyme is required?
The transfer of an amino group from an amino acid to α-ketoglutarate, forming glutamate and a keto acid.
Coenzyme: Pyridoxal phosphate (PLP) – derived from vitamin B6.
74
What is the role of glutamate in amino acid metabolism?
Collects amino groups from other amino acids.
Undergoes oxidative deamination via glutamate dehydrogenase (GDH) to release ammonia (NH₄⁺).
75
Where does oxidative deamination of glutamate occur?
mitochondrial matric of hepatocytes
76
what is transdeamination
The combined action of an aminotransferase (transamination) and GDH (deamination).
77
How is excess ammonia transported safely in the blood?
By converting glutamate to glutamine (via glutamine synthetase).
Glutamine carries ammonia to the liver, where glutaminase releases it.
78
How is ammonia transported from muscle to the liver?
Muscle converts pyruvate + NH₃ → alanine.
Alanine travels to the liver, releases NH₃ for urea formation, and pyruvate → glucose (returned to muscle).
79
What is the purpose of the glucose–alanine cycle?
Removes nitrogen from muscle.
Provides energy to muscle via recycled glucose.
80
How are the urea cycle and citric acid cycle linked?
Fumarate (from the urea cycle) enters the CAC.
Aspartate (from the CAC intermediate oxaloacetate) contributes nitrogen to the urea cycle.
81
What are glucogenic amino acids?
Amino acids whose carbon skeletons are converted into glucose precursors (e.g., pyruvate or CAC intermediates).
82
What are ketogenic amino acids?
Amino acids that are converted into acetyl-CoA or acetoacetate, used for ketone body or fat synthesis.
83
Which amino acids are exclusively ketogenic?
Leucine and Lysine.
84
In which cellular compartment(s) does the urea cycle takes place?
mitochondria and cytoplasm
85
Which amino acid is directly involved in the urea cycle and is also regenerated during the process?
Arginine
86
What is cancer?
Abnormal and uncontrolled cell growth derived from a single abnormal cell that can invade tissues and spread to other parts of the body.
87
Hallmarks of Cancer (Hanahan & Weinberg)
Self-sufficiency in growth signals
Insensitivity to anti-growth signals
Evasion of apoptosis
Limitless replicative potential
Sustained angiogenesis
Tissue invasion and metastasis
Reprogrammed energy metabolism
Evasion of immune destruction
88
What are cancer-critical genes? what are the 2 main classes
Genes repeatedly altered in human cancers that control growth, division, and genome stability.
1. Oncogenes/ Proto- oncogenes
2. Tumour suppressor genes (TSG)
89
Tumour Suppressor Genes (TSG)- what are they, what's their function, what happens when they're lost
A gene that prevents uncontrolled cell proliferation and maintains genomic stability.
Function= Control cell cycle checkpoints, DNA repair, and apoptosis.
Lost= Loss of growth control, genomic instability, resistance to apoptosis, and tumour formation.
90
What is cancer metabolism characterised by?
Increased glycolysis, altered nutrient use, and metabolic reprogramming to support rapid growth.
91
What is the Warburg Effect?
Cancer cells rely on aerobic glycolysis—they ferment glucose into lactate even with sufficient oxygen.
Beneficial for cancer cells as enables rapid ATP generation and supplies building blocks for growth.
92
What are xenobiotics?
Foreign chemical substances not naturally produced by the body.
can be toxic, mutagenic, or carcinogenic if not metabolised.
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