Metabolism Flashcards
What is metabolic rate
energy used per unit of time (kcal per day)
RMR and BMR
Resting metabolic rate (RMR) is energy needed to sustain resting individual
Basal metabolic rate (BMR) is the minimal awake rate of energy expenditure. It differs from RMR as it is measured under specific conditions that will influence MR.
What regulates basal metabolic rate
Basal Metabolic rate is regulated by thyroid hormones T3 and T4
Macromolecules after digestion
Glucose
- Stored as glycogen (glucose molecules joined together)
- Can be converted into amino acids or fat
- Main short term fuel source, oxidized for energy
Fatty Acids
- Stored as fat (triacyl glycerides or TG’s)
- TG’s are 3 fatty acids and a glycerol backbone
- FA can be oxidized for high energy yield
- Cannot be converted into glucose or AAs
Amino Acids
- Stored as protein polymers of AAs
- Not primary energy source except in starvation (GH protection)
- Excessive AAs are converted to glucose, fats or oxidised
Intermediary metabolism
Intermediary metabolism is the degradation and synthesis of carbs, proteins and fats.
What is metabolism
Refers to all chemical reaction within the body cells, provides energy to maintain homeostasis.
Catabolic + anabolic reactions
Catabolic and anabolic reactions
Catabolic reactions - breakdown larger molecules into smaller parts yielding energy
Anabolic - synthesis of larger molecules from smaller constituent parts requiring energy
Energy yield (carbs, fats, proteins)
Energy yield from carbs and proteins is similar while lipids give over double
Key considerations around the liver
- GI capillaries drain into the hepatic portal vein which will lead to the liver. This means that first pass metabolism occurs in the liver
- This is linked closely to pancreatic blood supply so hormones (insulin/glucagon) exert their effects at the liver first
- Liver stores glycogen and can perform glycogenolysis to break this down when required. It can also perform glycogenesis. Release to rest of body.
- The liver can also synthesis new glucose via gluconeogenesis using lactate or AAs
- Can synthesis ketones (energy substrate) via ketogenesis from fatty acids and AAs. This occurs as an ALTERNATIVE energy source from carbs (when they are scarce)
- Synthesis lipids from glucose or AAs via lipogenesis (fatty liver, high carb diet will cause fat storage in liver and can occur in SkM)
What is glycogenesis
Glycogenesis - synthesises glycogen from glucose, occurs when glucose supplies exceed demand for ATP. Requires energy and used glycogen synthase.
What is glycogenolysis
Glycogenolysis - breaks down glycogen to release glucose. Stimulated by low blood glucose. Glycogen phosphorylase.
Key considerations around SkM
- Utilises glucose within cell which differs from liver as it doesn’t go into circulation. This is during fed state and activity
- Lipids used as energy during fasting
- Stores glucose and glycogen which can ONLY be used in muscle cells via glycogenesis and glycogenolysis
Key considerations around Fat
Site of lipid storage (TGs) and release. Also has endocrine function releasing hormones called adipokines to regulate apatite.
Release of glycerol backbone and FAs during starvation. Glycerol used to make new glucose in liver and FA are alternative energy source to glucose
Why does the brain need a constant supply of glucose
Glycogen is not stored in neurons so needs constant supply via blood. Cant convert glycogen to glucose.
Glia cells can store and release but only small amount and at local level
Catabolic and anabolic reactions
Catabolic reactions - breakdown larger molecules into smaller parts yielding energy
Anabolic - synthesis of larger molecules from smaller constituent parts requiring energy
Key catabolic hormones
Mobilisation (between meals):
- Glucagon
Active in starvation (below)
- Catecholamines
- Cortisol (stress hormone from adrenal)
- GH (fats and carbs)
Key anabolic hormones
Promote storage:
- Insulin
- GH (protein only)
Key aspects of insulin
Only hormone that can increases blood glucose
- Stimulated by HIGH blood glucose i.e it is a anabolic hormone
- Secreted by beta cells of pancreatic islets
- Causes facilitated diffusion of glucose into tissue cells
- Also active transport of AAs into tissue cells
- Increase storage of glucose FA and AA
Key aspects of glucagon
- Simulated by LOW plasma glucose
- Stimulates glycogenolysis and gluconeogenesis at the liver to cause increased plasma glucose
- Stimulates fat breakdown (lipolysis) at adipose tissue to alloe fat to be used by tissue cells leading to glucose sparing
- Secreted by alpha cells of pancreatic islets
- Mobilises glucose, fatty acids and AA from stores to blood
Key 3 underlying mechanisms of metabolic syndrome
- Fat accumulation - visceral/intra abdominal fat
- Impaired insulin sensitivity (insensitivity) → insulin resistance
- Low grade chronic systemic inflammation - pro inflammatory state
What disease can result from metabolic syndrome
- Type 2 diabetes
- Non alcoholic fatty liver disease (lipogenesis)
- Cardiovascular disease
Physiological criteria for metabolic syndrome
- Impaired glucose regulation or inulin resistance → hyperglycaemia (increase BG)
- Abdominal obesity
- Hypertriglycermia (increased TGs in glood)
- Low level of HDL cholesterol (good cholesterol)
- Hypertension
- Microalbuminuria (albumin in urine)
What are the primary cell type for adipose tissue
Adipocytes are primary cell type of adipose tissue. Synthesis compounds that regulate metabolic homeostasis.
How does fat accumulation change inflammatory profile
- Fat mass increases in size, increasing distance between cell and blood vessels
- This causes necrosis
- Activating the immune system to clean this up, which will cause a change to pro inflammatory profile (excess immune cells)
This change of inflammation spills over into systemic and then other tissue creating low grade chronic systemic inflammation.
How does insulin insensitivity occur and what does this mean
Insulin sensitivity is where insulin levels are normal or slightly elevated (pancreatic beta secret in response to high glucose) but the target cells become less sensitive to insulin. Issue with cell signalling inside the cell.
Consequences include hyperglycemia and compensatory hyperinsulinemia (increased insulin).
Glucose uptake into SkM, liver and adipose tissue is compromised.
How can metabolic syndrome lead to CV disease
Low levels of HDL in metabolic syndrome and hypertrigylcemia.
Leads to CV disease such as atherosclerosis (plaque build yo effecting blood flow)
Build up causes damage to vessel wall which can lead to aneurism or stoke.
Two types of diabetes
T1 - is lack of insulin secretion
Immune destruction of the beta cells (type 1)
Can have B cell failure T1
T2 - insulin insensitivity Elevated insulin (from high glucose) continues over time (metabolic disease) T2
Pancreatic cells that secret hormones
Alpha cells - glucagon
Beta cell - insulin
Why is impaired glucagon secretion better than impaired insulin
Impaired insulin secretion results in diabetes and cannot be compensated.
Impaired glucagon secretion can be compensated
Long term effects of diabetes
Shorter life expectancy
Hyperglycaemia leads to excessive glycosylation of proteins (sugar residue onto proteins) which leads to:
- Vascular damage - atherosclerosis, MI, stroke
- Diabetic retinopathy - blindness
- Diabetic nephropathy - renal failure
- Neuropathy - Central and peripheral NS damage
Characteristics of diabetes
Disease of impaired carb fat and protein metabolism
Characterised by hyperglycemia
Either T1 or T2
Wat are the energy carriers used in metabolic pathways
ATP
NADH and FASH2 are electron transport carries
They are high energy molecules like ATP used in oxidative phosphorylation
Three processes in carb metabolisms
Glycolysis -> Citric acid cycle-> oxidative phosphorylation
Process of carb metabolism
Glycolysis is glucose to pyruvic acid (x2). This requires 2 ATP to starts and provides 4 (net 2). Also provides 2 NADH + H.
This occurs outside the mitochondria (in cytosol)
Pyruvic acid then becomes Acetyl CoA inside the mitochondria yielding another 2 NADH +H. Acetyl CoA can be fed into the citric acid cycle, providing an addition 2 ATP. Citric acid cycle also provides 6 NADH + H and 2 FADH2.
Oxidative phosphorylation than occurs provided 28 ATP.
Therefore from one glucose molecule 30 ATP can be gained.
In aerobic situation (no O2) still gives ATP just not as much as oxidation cannot occur.
What are the 4 main fat metabolic pathways that all converge to form Acetyl CoA and where does this then go
- Lipolysis - hydrolysis (breakdown) of mainly TGs to produce glycerol and FAs
- Glycerol
- Beta oxidation - conversion of FAs into Acetyl CoA
- Lipogenesis - cholesterol and other lipid synthesis
- Ketogenesis - formation of ketone bodies (FA → acetyl CoA → ketone bodies). Only occurs if low carbs, too much Acetyl CoA into TCA (no glucose)
The Acetyl CoA is the fed into the citric acid cycle
In the absence of mitochondria what happens to pyruvic acid
In absence of mitochondria pyruvic acid cannot go into Acetyl CoA so it become lactic acid
Process of protein metabolism
Transamination - an amine group is switched from an amino acid to a keto acid
- Amino acids turned into keto acid and ammonia
Separate pathway for both the amine group and the keto acid
Keto acid modification - Keto acids formed during transamination are altered so the can easily enter the citric acid cycle
Oxidative deamination - The amine group of glutamic acid is removed as ammonia and combined with CO2 from urea to be excreted in urine
Where can keto acids enter metabolism
In glycolysis or directly into the TCA cycle
