Overview of Human Nutrition - link between nutrition & metabolism

Metabolism

Metabolism is sum of processes involved in taking nutrients in food, assimilating & using them to maintain body tissue & provide energy.

There are two categories in metabolism.

Anabolism

Anabolism is the synthesis of larger molecules from small molecules. This process requires energy.

Catabolism

Catabolism is the breakdown of large molecules into small molecules. This process liberates energy.

Role of nutrients in metabolism

Macronutrients:

Macronutrients act as the body fuels & precursors for other synthetic reactions. Macronutrients are:
- Carbohydrate
- Lipids
- Proteins
- (Minerals)

Micronutrients:

Micronutrients are the facilitators for metabolic reactions.
- Vitamins
- Trace elements

Digestive tract, liver & pancreas, heart & blood vessels and kidney are the main organs involving digesting, absorbing, transporting & excreting of nutrients.

Organs & their metabolic roles  

• Metabolic reactions of every organ contributes to body's ability to function normally & maintain health. 

• Metabolic reactions also use or release energy & therefore affect body weight with consequences to health

Body's metabolic work

• Metabolic work of body cells requires energy
• Foods supply energy
• Chemical reactions release stored energy from energy yielding nutrients
• Energy becomes available to do the work

Relationship between food supply & energy need

- Stored nutrients and Ingested foods supply the fuels for energy need.
- Catabolic reactions (oxidation pathways) occur

- Create ATP, CO₂, NH₃ , H₂O, simple products and precursors
- ATP is the carrier of the metabolic energy
- Anabolic reactions (synthetic pathways) occur
- Energy need for osmotic work, mechanical work, complex biomolecules and other cellular work

• ATP is the energy currency of cells 
• Cells cannot accumulate ATP
• ATP is converted to creatine phosphate, stored & rapidly regenerated

ATP react with Creatine while there is Creatine Kinase (CK)  enzyme and form Creatine  Phosphate and ADP. When there is a energy requirement, Creatine Phosphate react with ADP  while there is Creatine Phosphokinase (CPK) enzyme and form ATP and Creatine.

Anabolic Reactions

Anabolic reactions include the making of glycogen, triglycerides, and protein; these reactions require differing amounts of energy.

• A glucose molecule combine with an another glucose molecule through glycogenesis and form Glycogen. This process uses energy.
• A glycerol molecule combine with three fatty acids through lipogenesis and form Triglycerides. This process uses energy.
• Amino acids combine  with another amino acid through protein synthesis and form protein. This process uses energy.

Catabolic Reactions

Catabolic reactions include the breakdown of glycogen, triglycerides, and protein; the further catabolism of glucose, glycerol, fatty acids, and amino acids releases differing amounts of energy. Much of the energy released is captured in the bonds of adenosine triphosphate (ATP).

• Glycogen breakdown into Glucose through glycogenolysis. Then glucose yields energy through glycolysis (TCA).
• Triglycerides breakdown into Glycerol and Fatty acids through lipolysis. Then Glycerol and Fatty acids yield energy.
• Protein breakdown into amino acids through proteolysis. Then amino acids yields energy.

Living cells are self regulating chemical engines, adjusted for maximum economy. Cells have a complex, intricately regulated system of energy producing & energy utilizing reactions. This helps to perform various types of work needed to: maintain, grow, reproduce & perform tissue specific cellular functions.

• Energy supply in the diet is mainly in the form of macromolecules.

             - Carbohydrates
             - Proteins
             - Fats

• Macromolecules are broken down to smaller molecules during digestion

          - Monosaccharides
          - Amino acids
          - Fatty acids

These FUELS NUTRIENTS, transported as simple molecules, stored as macromolecules, oxidized to produce energy (catabolism), used for synthesis of biomolecules (anabolism)

Storage of fuels as macromolecules

Glucose:
Stored as glycogen in hydrated form (small energy cost)
Also stored as triacylglycerols in anhydrous form (high energy cost)
Free Fatty Acids:
Stored as TAG (triacylglycerides) (small energy cost)
Amino acids:
No store
Present in tissues as proteins
Reserve in muscle

"Energy homeostasis"
All metabolic pathways do not operate at maximal capacity at all times.

• Strategy

          Store energy when available
          Mobilize stored energy when in need

• Major tissues of the body work together to maintain a constant supply of oxidizable fuels (eg. glucose) in:

             - well-fed state
             - fasting or starving state
             - or during exercise

• Catabolism increased in: food deprivation and stress
• Anabolism increased in: relative energy excess, growth, and regeneration of cells

Nutrients (fuels) in blood

• Glucose

       Sources are: Dietary carbohydrates (CHO), glycogen stores and gluconeogenesis

• Free fatty acids (FFA: NEFA)

        Sources are: Dietary fats, lipid stores, synthesis from CHO

• Amino acids

        Sources are: Dietary protein, tissue protein

• Ketone bodies

        Sources are: Produced from FFA & some AA

• Glycerol

        Sources are: TG breakdown

• Galactose

        Sources are: Dietary intake (milk lactose)

• Fructose

        Sources are: Dietary intake (Sucrose, fructose)

• Ethanol

        Sources are: Dietary intake, gut fermentation


Fuels utilized by different tissues

• Brain: Glucose, Ketone bodies (in prolonged starvation)
• Muscle: Glucose, FA, BCAA, Ketone bodies (KB) (Starvation)
• Liver: Glucose, FA, AAs, SCFA, alcohol
• Kidney: Medulla: Glucose

                        Cortex: Glucose, FA, KB

• Adipose tissue: Glucose, FA
• GIT: Small Intestine: Glu, Gln, KB (Starvation)

                   Large Intestine:  SCFA, Gln, Glu

•  RBC: Glucose
• Lymphocytes, M'phages: Gln, Glu

What is homeostasis?

• Ability of organ systems to work together to maintain a relatively stable internal environment
• Two major homeostatic control systems in the body

       - Nervous system - receives & transmits information via electrical impulses between nerve cells
       - Endocrine system - communicates via chemical messengers in the blood ie. hormones, cytokines

• Metabolic pathways must be coordinated so that production of energy or synthesis of end products meets the needs of the cell
• Individual cells do not function in isolation, but are a part of a community of interacting tissues
• Regulatory signals informing an individual cell of the metabolic state of the body include:

          - specific regulatory metabolities
          - hormones & other mediators

• Communication between major tissues (liver, brain, muscle and adipose tissue) occur through hormones, nervous system and substrate availability

Hormonal regulation of blood glucose & energy storage

 Insulin promotes energy storage

• Homeostasis disturbed by rising blood glucose levels
• Beta cells release insulin
• Promotes uptake of glucose into some cells (muscle and adipose tissue)
• Promotes conversion of glucose to glycogen in liver and skeletal muscle cells (glycogenesis)
• Promotes protein synthesis in muscle cells
• Promotes fat synthesis in adipose tissues
• Blood glucose concentration declines
• Homeostasis restored into normal blood glucose
  

Glucagon promotes mobilization of stored energy

• Homeostasis disturbed by decreasing blood glucose levels
• Alfa cells release glycogen
• Promotes breakdown of glycogen to glucose in the liver (glycogenolysis)
• Promotes breakdown of fatty acids in adipose tissue and ketone production in the liver (ketogenesis)
• Promote use of non-carbohydrate sources to make glucose in the liver (gluconeogenesis)
• Blood glucose concentration rises
• Homeostasis restored into normal blood glucose

Fight or flight response

• Other hormones can also increase blood glucose when cells have immediate need for energy
• These includes adrenalin & cortisol produced by adrenal glands

             - not involved in day to day glucose homeostasis
             - stimulate liver & muscle glycogenolysis in response to stress

Gluconeogenesis

• Gluconeogenesis - synthesis of Glucose from non-Carbohydrate substances: additional source of glucose
• Glycogen - small reserve

          Glycogenolysis - effective short term solution to provide cells with glucose

• FA cannot produce glucose
• Glucagon & adrenalin stimulate gluconeogenesis & insulin inhibits it

Ketone bodies spare glucose

• Increased gluconeogenesis has negative consequences as muscle protein breakdown occurs to produce AA for gluconeogenesis
• To minimize this alternative fuel used ie. Ketone bodies derived from FA
• KB can serve as fuel for heart & skeletal muscle, kidney cortex & brain (prolonged fast)
• KB spare glucose for glucose dependent tissues 

Ketosis when KB production >>> utilisation

Impaired glucose tolerance & diabetes

• Decreased insulin - due either to reduced action or to decreased secretion
• Glucose accumulates in blood - hyperglycaemia & increase HbA_1c
• When blood glucose level exceeds renal threshold - glycosuria 
  
    Fate of glucose & other fuels
  
  
  • Brain oxidize Glucose for energy, rarely use KB
  • Adipose tissue store Glucose and Fatty Acids as TG. Then release Fatty Acids when there is an energy requirement
  • Muscle store Glucose as glycogen energy reserve, rarely use FA
  • Liver oxidize or store Glucose as Glycogen, rarely use FA. Then release Glucose and KB when there is an energy requirement
  
   Plasma lipoproteins
  
  
  • Chylomicrons (CM) - transport exogenous TG (dietary) assembled in the intestine
  • VLDL - transport endogenous TG synthesized in liver
  • LDL - forward transport of cholesterol 
                     - produced in plasma during intravascular metabolism of VLDL
  •  HDL - reverse transport of cholesterol
                      - produced in liver & intestine
  
• Lipid metabolism
  

Metabolic changes in the fed state

• Influx of glucose and amino acids into the circulation after a meal
• Insulin secreted during & after the meal
• Stimulates glycogenesis & lipogenesis
• Stimulates protein synthesis
• Stimulates glycolysis & TCA
• Chylomicrons (products of lipid digestion) enter systemic circulation via lymphatic system

Metabolic changes in the fasted state

• No fuel enters the gut & concentration of glucose in portal blood falls
• Insulin secretion decreases & glucagon secretion increases
• Early fasting: Liver - reduce Glycogenesis

                                          - increase Glycogenolysis

•  Later: Muscle protein catabolism increase

                           - alanine, glutamine released
                           Adipose tissue - TG synthesis reduced, lipolysis increase

Metabolic changes in prolonged fasting

•  Alfa cells of pancreas secrete glucagon
• Adipose tissue release fatty acids and glycerol
• Glycerol converts to glucose
• Fatty acids converts to ketone bodies
• Brain use ketone bodies and glucose
• Muscle tissues breakdown proteins into amino acids and release glutamine and alanine
• Glutamine converts to alanine
• Alanine convert to glucose and urea
• Muscle tissue use alanine and fatty acids

Fuel availability and hormonal changes in starvation

Metabolic changes during pregnancy

During pregnancy starve-feed cycle is perturbed
Between meals

• Pregnant women enter starved state more rapidly than non-pregnant women because of increased consumption of glucose and amino acids by the fetus
• Plasma glucose, amino acid and insulin levels fall rapidly
• Lipolysis and ketogenesis stimulated
• Fetus use lactate, Glucose from liver glycogen, fatty acids from adipose tissue fat, ketone bodies derived from fat, and amino acids from muscle tissue proteins

Metabolic changes during lactation

• In late pregnancy placental hormones:
  

           - promote uptake of FA into the mammary gland
           - promote development of milk secreting cells and ducts

• During lactation mammary gland utilizes glucose for lactose and triglyceride synthesis and is the major energy source

Metabolic inter-relationships during lactation 

• Amino acids are used for protein synthesis
• Triglycerides  in chylomicrons and VLDL are utilised as sources of FA for triglyceride synthesis
• If these are not supplied in the diet, gluconeogenesis,  lipolysis and proteolysis must supply them
• This leads to maternal malnutrition and poor quality milk 

Recommended reading

• Human nutrition 11th Edition 2005 Ed. Geissler CA, Powers HJ, Elsevier, UK
• Text book of Biochemistry with clinical correlations chapter 20, Ed. T Devlin, Wiley-Liss, USA
• Nutrition and diet therapy Schlenker ED (latest edition)
• Nutritional Sciences: from fundamentals to food Ed. M. McGuire, K A Beerman, Thompson Wadsworth USA, 2007
• Understanding nutrition 11th edition E Whitney, S R Rolfes, Wadsworth, USA