Pyruvate's third fate is to generate acetyl-coA:

pyruvate+HS-CoA +NAD+ --> Acetyl CoA +CO2+NADH

This is known as the

The acetyl-coA formed is committed into entry to the

and can ultimately produce ATP via oxidative phosphorylation

The pyruvate dehydrogenase complex which allows the link reaction to occur is huge, it consists of 3 enzymes and 5 cofactors

3 enzymes are:

Pyruvate decarboxylase with a

prosthetic group

with a lipoamide prosthetic group

Dihydrolipoyl dehydrogenase with an

prosthetic group

The other two cofactors are NAD+ and

It starts with

trimers of lipoamide reductase-transacetylase

Then

dimers of dihydrolipoyl dehydrogenase

and 12 dimers of pyruvate decarboxylase

Thiamine pyrophosphate loses a proton readily and the resulting carbanion attacks that of pyruvate to yield hydroxyethyl-TPP

A deficiency of

is a cause of Beri-Beri whose symptoms include damage to the peripheral nervous system, weakness of the muscles and decreased cardiac output

FAD accepts and donates 2 electrons with

The pyruvate dehydrogenase complex: Decarboxylation of

to give hydroxyethyl-TPP, oxidation and transfer of

group to lipoamide to give acetylipoamide

Transfer of acetyl group to coA to give acetyl-coA, leaving reduced lipoamide.

Regeneration of oxidised lipoamide by FAD generating FADH2, regeneration of FAD by NAD+

General strategy of amino acid degradation is to remove the

whilst the carbon skeleton in funnelled into the production of

or fed into the Krebs cycle

Degradation of all 20 amino acids gives rise to only 7 molecules: pyruvate, acetyl-coA, acetoacetyl-coA, alpha-ketoglutarate, succinyl-coA, fumarate and oxaloacetate

It can involve

reactions where an amine group from one amino acid is transferred to a keto acid forming anew pair of amino and keto acids

Alanine undergoes transamination by the action of the enzyme alanine

Pyruvate can enter the Krebs cycle while glutamate can be converted into alpha-ketoglutarate

The sum of all processes in the body is

It is measurable as oxygen uptake, carbon dioxide release and production of

Muscle- Accounts for 40% of total body mass, it has periods of very high ATP requirement

It relies on carbohydrate and fat

Skeletal muscle is capable of large and rapid increases in ATP demand during exercise

Cardiac muscle accounts for 1% of body mass but uses

of the resting metabolic rate. The heart must beat constantly and is designed for completely

respiration and is adapted with a large number of mitochondria.

Brain and nervous tissue- Accounts for

of total body mass, it uses 20% of the resting metabolic rate as it has continuous high ATP requirement

The brain and nervous tissue can't utilise

Thus it requires a constant supply of glucose for metabolism

If there is too little, then

occurs- faintness or even a coma

If there is too much then

occurs - irreversible damage

Adipose tissue- Accounts for 15% of body mass, long term storage site for

Liver- Accounts for 2.5% of body mass, utilises

of resting metabolic rate. It has the body's main store for carbohydrates -

It is the immediate recipient of nutrient absorbed at the intestines. It has a wide repertoire of metabolic processes such as glycolysis and gluconeogenesis

Central role of maintaining blood glucose at

It also contributes to lipoprotein metabolism

Gluconeogenesis- This is making glucose or glycogen from

It is only a function of the liver, it requires ATP

It is not an exact reversal of glycolysis, there are different enzymes

Amino acid breakdown leads to amino acids, they can be fed into the TCA cycle, make acetyl-coA and make

When they do this, they let off urea as a waste product

Fat breakdown leads to fatty acids and

Fatty acids can make acetyl-coA, some amino acids but they can't undertake

as they don't feed into the TCA cycle. Glycerol can enter the glycolysis pathway

Fatty acids can cause accumulation of acetyl-coA when beta-oxidation is highly active

This leads to the accumulation of

bodies such as acetoacetate, acetone and beta-hydroxybutyrate

These can be used by the

where glucose is low and the heart under normal circumstances

During aerobic exercise - The liver receives

and it is transported to the muscle via the blood. Fatty acids in the blood also contribute

During anaerobic- Demand for glucose increases, this causes

to be broken down to form glucose as an immediate source. The liver is still providing glucose. ATPases in the muscle work harder as contractions increase glucose transport

Eventually

is made in the muscle which is taken to the liver via the bloodstream. The liver metabolises lactate back to

and regenerates glucose

Glucose metabolism is controlled at a step strongly dependent on enzyme activity, a step unique to the pathway and a step early in the pathway

It is controlled by the

of the reaction - negative feedback, a signal molecule that relays information from other pathways

Eating increases blood glucose causing increased uptake into cells. Muscles have hexokinase I which has high glucose

Its also sensitive to G6P inhibition. Therefore at low conc of glucose (like during fasting) the glucose would go straight to the muscle and be converted to

there for use in muscle metabolism immediately.

Consequently the liver has hexokinase IV which has low glucose affinity and is less sensitive to G6P inhibition. It'd only catalyse the reaction in the liver at high conc of glucose which is not needed during fasting. At high conc, the glucose would be taken up by the liver to be

G6Pase in the liver also catalyses the reaction to convert G6P to glucose.

diabetics can't make insulin

diabetics have reduced responsiveness to insulin and impaired islet function

Metabolism is controlled as if for starvation regardless of dietary uptake resulting in hyperglycaemia, increase in plasma fatty acids and lipoproteins with possible CVS complication, increase in ketone bodies and hypoglycaemia

Insulin is made and secreted from

in the islets of Langerhans in the

Secreted by increasing glucose resulting in increased ATP thus changing gene expression, opening voltage gated calcium channels, causing the vesicles containing insulin to fuse with the membrane

Glucagon is also important in diabetes, insulin deficiency and thus relative excess of glucagon leads to increased output of

and thus

occurs. In diabetics, who are in a state of prolonged fasting, the glucagon/insulin ratio

The adipose tissue begins to hydrolyse to provide

to provide fatty acids for metabolism.

Glucose is not transported to muscle and liver as it isn't detected or insulin doesn't work thus:

Gluconeogenesis

via protein breakdown and glycerol generation thus hyperglycaemia

Fatty acid breakdown produces

that contribute to ketoacidosis - they're needed substitute the brain's requirement for glucose

Glycolysis and the Krebs cycle provide the starting point for many biosynthetic reactions. The amino acids, nucleotides, lipids, sugars and other molecules can be produced

NADPH takes part in

reactions (build things up) whereas NADH takes part in

reactions. The use of different cofactors for different sets of reactions allows electron transport in catabolism to be separate to from anabolism

NADP+ is related to NAD+ but has a

ring attached to one of the ribose rings. It has the same mechanism of transfer as NAD+, it picks up a

but it gives a slightly different conformation meaning it can bind to different enzymes than NAD+

It is a cofactor in the biosynthesis of RNA and DNA

NADPH also helps to catalyse the final reaction of several that leads to the synthesis of

Mitochondria are the powerhouse of the cell, they generate the bus of cellular ATP. They have two membranes, the inner and outer.

The outer membrane limits the size of the mitochondrion and the inner membrane have folds called

The reactions of oxidative phosphorylation occur on the

whereas the krebs cycle reactions take place in the

The cristae increases the

of the inner membrane so more reactions can take place. In some cells e.g sperm mitochondria distribute themselves where ATP is rapidly consumed

Believed to be evolutionary descendants of

that established an

relationship with the ancestors of eukaryotic cells.

This is thought to have occurred very early on and following this, the majority of genes coding for mitochondrial function were translocated to the nuclear genome

There is evidence for this theory: Mitochondria can only arise from pre-existing mitochondria and

Mitochondria possess their own

and it resembles that of prokaryotes being a single circular molecule of DNA with no associated histones

Mitochondria have their own

synthesising machinery which resembles that of prokaryotes

The first amino acid of their transcripts is always

as it is in bacteria and not methionine (Met) that is the first in eukaryotic protein

A number of antibiotics that act by blocking protein synthesis in bacteria also block protein synthesis within mitochondria and chloroplasts

NADH donates the electrons it carries along with a proton to components in the electron transport chain. The protons are donated to the

surrounding the enzyme complex and the electrons join the electron transport chain. Within the mitochondria, the coenzymes are re-oxidised by oxygen

Oxidative phosphorylation takes place in two steps:

The translocation of

from within the matrix to the

The pumped protons are allowed back into the matrix through a specific channel which is coupled to an enzyme that can synthesis ATP called

This generates proton-motive force consisting of a pH gradient and a