26. 3. 2019
Pathophysiology
of metabolism of proteins
Energy
homeostasis
METABOLIC PATHWAYS
Intermedial metabolism
METABOLISM STAGES
Figure 24.3
• Nutrients containing energy are
processed in three stages:
1. Digestion – food processing;
nutrients are transported to the
tissue
2. Anabolism and catabolic
intermedial products forming,
where nutrients are:
• bound to lipids, proteins and
glycogen, or:
• cleaved in metabolic
pathways to pyruvate and
acetyl CoA.
3. Oxidative phosphorylation –
nutrients are catabolized to CO2,
water and ATP
Resetting signals of the central and peripheral clocks.
Froy O Endocrine Reviews 2010;31:1-24
©2010 by Endocrine Society
LEPTIN
INSULIN NPYNEURON
AgRPNEURON
POMCNEURON
CARTNEURON
BLOOD VESSEL
NPY AgRP
α-MSH
Increased food intake Decrease food intake
α-MSH
RECEPTORs
OREXIGENIC-ANOREXIGENIC PATHWAYS
Drug Insight: the functions of ghrelin and its potential as a multitherapeutic hormone
Masayasu Kojima and Kenji Kangawa
Nature Clinical Practice Endocrinology & Metabolism (2006) 2, 80-88
Regulation of food appetite
INTERNAL CHANGES OF NUTRITION MOLECULES
 Glycogenesis
 Lipogenesis
 Glycogenolysis
 Gluconeogenesis
Overview of the mechanisms and consequences of epigenetic regulation by nutritional compounds.
Modulation of different classes of chromatin writers-erasers by phytochemicals (left panel). Genes encoding
absorption, distribution, metabolism, and excretion (ADME) proteins can be epigenetically regulated and
thereby determine individual nutritional responses. Epigenetic modification of disease-related genes can
contribute to diagnosis (biomarker) as well as disease prevention or progression (right panel).
2015 Mar 25;7(1):33.
doi: 10.1186/s13148-
015-0068-2.
eCollection 2015.
From inflammaging
to healthy aging by
dietary lifestyle
choices: is
epigenetics the key
to personalized
nutrition?
Vel Szic KS1,
Declerck K1,
Vidaković M2,
Vanden Berghe W1.
The loss of universal helminth infection as occurred in earlier human evolution may alter the numbers or types of
bacterial and fungal commensals and thus affect normal mucosal tissue homeostasis. In susceptible or highly
exposed individuals, such alterations might alter the balance between immunotolerance, immunosurveillance and
nutrient extraction. This imbalance may contribute to the appearance of inflammatory systemic dysregulation at
mucosal surfaces, resulting in increases in asthma and allergic diseases, particularly in the setting of
environmental changes that have increased exposure to indoor allergens and pollutants, and even to increases in
obesity, which can be a risk factor for severe asthma.
METABOLISM
 Quantitative evaluation
(energetic)
 Qualitative evaluation (sufficient
and suitable proportion of
proteins, lipids and sugars)
 Anabolism
 Catabolism
METABOLISM OF SUBSTANCE:
 -anabolism = more complicated products are
synthetized from simple absorbed compounds
(s.c. assimilation) – energy is used (endergonic
reaction)
 -catabolism = portion of absorbed compounds
is cleaved to simpler ones (dissimilation) –
energy is released (exergonic reaction)
ENERGY METABOLISM
 - most food compounds are used as a
energy source
 1g of sugars 17.22kJ
 1g of lipids 39.06kJ
 1g of proteins 23.73kJ
REGULATION OF METABOLIC PROCESSES
Neuro-immuno-endocrine regulation using hormones:
(insulin, glucagon, growth hormone, glucocorticoids, T4
and T3, reproduction hormones:
 Liver
 Adipose tissue
 Skin
 Kidneys
 Respiratory and cardiovascular system
PROTEIN METABOLISM
 Non essential amino acids can be formed by
transamination (= transfer of amino acid group to
keto acid).
 When using for energy formation, they undergo
oxidative deamination. NH3 and keto acids are side
products of the reaction. NH3 is changed to urea
and excreted by urine.
 Amino acids are not stored in the body.
PROTEINS
 Main building material of cells and tissues, enzymes,
some hormones and compounds of pigments
 Food sources: animal(contain all AAs) and plant (not
all contain essential AAs)proteins  digestion in
stomach – pepsin (from pepsinogen, activated by
HCL) and small intestine – trypsin, aminopeptidases
(cleave N-terminal AAs), carboxypeptidases (cleave
C-terminal AAs), dipeptidases (cleave dipeptides) –
and AAs  absorption to v. portae in presence of vit.
B6
 Condition for adequate protein digestion- they must
be denaturized (cooking)
INTERNAL CHANGES OF NUTRITION MOLECULES
METABOLIC REACTION OF LIPIDS AND PROTEINS
Table 24.2.2
CATABOLISM OF PROTEINS
CATABOLIC STATES
Are induced by dysregulation of metabolic events by
inflammation (cytokines), stress (A, GCs), chronic
immobilization.
 Acute severe diseases (adaptation on starvation
decreases, protein malnutrition can develop).
 Cancer - cachexia (cytokines TNF, IL-1 and IL-6).
 Trauma, burns, fever, painful states, AIDS (wasting
syndrome).
ORGAN CHANGES IN PROTEIN AND ENERGY
DEFICITS
 Loss of body weight (drop of 40% is leading to death).
 ECT volume is not changing or relative expansion of
ECT against ICT. When oncotic pressure was
decreasing, edema could develop.
 Decreased cardiac output.
 Decreased function of respiratory system due to
decreased contractility of respiratory muscles.
 Decreased stomach motility and stomach production
of HCL
 Decreased exocrine function of pancreas
 Decrease liver mass with decrease proteins, lipids and
glycogen in secondary malnutrition
 In primary malnutrition liver mass increased due to lipids
infiltration and increased production of glycogen.
ORGAN CHANGES IN PROTEIN AND
ENERGY DEFICITS
 Kidney weight decreases.
 Increased ECT volume due to decreased osmotic gradient in
the kidney.
 Increased secretion in endocrine system.
 Immunodeficiency state (decrease of non specific immune
functions).
 Atrophy of the skin end GIT epithelia with functional lesions of
barriers against external environment.
 Decreased wound healing in severe protein malnutrition.
THE HUMAN STARVATION
 response is unique among animals in that
human brains do not require the ingestion of
glucose to function. During starvation, less than
half the energy used by the brain comes from
metabolized glucose. Because the human
brain can use ketone bodies as major fuel
sources, the body is not forced to break down
skeletal muscles at a high rate, thereby
maintaining both cognitive function and
mobility for up to several weeks.
HUMAN STARVATION
 This response is extremely important in human evolution
and allowed for humans to continue to find food
effectively even in the face of prolonged starvation.
 Initially, the level of insulin in circulation drops and the
levels of glucagon, epinephrine and norepinephrine
rise. At this time, there is an up-regulation of
glycogenolysis, gluconeogenesis, lipolysis, and
ketogenesis.
 The body’s glycogen stores are consumed in about 24
hours. In a normal 70 kg adult, only about 8,000
kilojoules of glycogen are stored in the body (mostly in
the striated muscles).
HUMAN STARVATION
 The body also engages in gluconeogenesis to
convert glycerol and glucogenic amino acids
into glucose for metabolism.
 Another adaptation is the Cori cycle, which
involves shuttling lipid-derived energy in
glucose to peripheral glycolytic tissues, which
in turn send the lactate back to the liver for
resynthesis to glucose. Because of these
processes, blood glucose levels remain
relatively stable during prolonged starvation.
HUMAN STARVATION
 However, the main source of energy during prolonged
starvation is derived from triglycerides. Triglycerides are
broken down to fatty acids via lipolysis. Epinephrine
precipitates lipolysis by activating protein kinase A,
which phosphorylates hormone sensitive lipase (HSL)
and perilipin. These enzymes, along with CGI-58 and
adipose triglyceride lipase (ATGL), complex at the
surface of lipid droplets. The concerted action of ATGL
and HSL liberates the first two fatty acids. Cellular
monoacylglycerol lipase (MGL), liberates the final fatty
acid. The remaining glycerol enters gluconeogenesis.
MALNUTRITION
 Malnutrition is a disorder in body
composition in which inadequate
macronutrient (protein, carbohydrate,
and fat) or micronutrient (vitamins,
minerals, and trace elements) intake
results in decreased body mass, reduced
organ mass, and most importantly,
decreased organ function.
NUTRITION: PROTEINS
 Adequate intake of protein is one of the
key nutritional factors to maintain
independence, predominantly by
preventing loss of muscle mass and
strength (sarcopenia), frailty and
associated comorbidities in later life.
SARCOPENIA
 A gradual decline in muscle mass is observed
from the third decade of life with a 30–50%
decrease reported between the ages of 40
and 80. Muscle strength is correlated with
muscle mass and rapidly declines after the
age of 50.
 The beginning of the fourth decade of life
might therefore be interpreted as the time
when muscle ageing process begins and for
this reason it is the optimal time for
implementing appropriate dietary changes, to
prevent or delay the onset of sarcopenia.
PERSONALITY TYPE D („DISTRESSED“ PERSONALITY)
 Type-D denotes the synergistic effect of negative affectivity
(tendency to experience negative emotions) and social
inhibition (tendency to inhibit self-expression).
 As a result, type-D patients experience more feelings of
anxiety, depression, and anger, but inhibit self-expression in
order to avoid disapproval by others.
 Type-D is associated with a four- to fivefold increased risk of
death or myocardial infarction in cardiac patients.
 Type-D personality was positively associated with the cortisolawakening
response, independently of age, sex, and body
mass.
Mundel P, Reiser J.Kidney Int. 2010 Apr;77(7):571-80.
Proteinuria as a cause of a loss of proteins
Mundel P, Reiser J.Kidney Int. 2010 Apr;77(7):571-80.
.
Mundel P, Reiser J.Kidney Int. 2010 Apr;77(7):571-80.
DĚKUJI VÁM ZA POZORNOST